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Sample records for endogenous norepinephrine levels

  1. DOPA, norepinephrine, and dopamine in rat tissues

    DEFF Research Database (Denmark)

    Eldrup, E; Richter, Erik; Christensen, N J

    1989-01-01

    We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...

  2. Mass spectrometric measurements of norepinephrine synthesis in man from infusion of stable isotope-labelled L-threo-3,4-dihydroxyphenylserine

    International Nuclear Information System (INIS)

    Suzuki, T.; Sakoda, S.; Ueji, M.; Kishimoto, S.

    1985-01-01

    The kinetics of stable isotope-labelled L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), an immediate precursor of (-)-norepinephrine, was studied to investigate the pharmacologic mechanism of its therapeutic effect on orthostatic hypotension in familial amyloid polyneuropathy (FAP) and on akinesia and freezing in parkinsonism. [ 13 C,D]-L-threo-DOPS was synthesized, and 100 mg of the compound was infused for 2 h into two normal subjects, two FAP patients and two patients with the degenerative diseases of the central nervous system. Labelled and endogenous norepinephrine in urine and plasma was assayed simultaneously by gas chromatography/mass spectrometry. The results indicate that the increase in norepinephrine in biological fluids after administration of L-threo-DOPS is attributable mostly to norepinephrine derived from L-threo-DOPS, not to pre-formed endogenous norepinephrine released by L-threo-DOPS

  3. Rapid adaptation of the stimulatory effect of CO2 on brain norepinephrine metabolism.

    Science.gov (United States)

    Stone, E A

    1983-12-01

    The present study examined the effects of exposure of rats to elevated environmental levels of CO2 on norepinephrine metabolism in the hypothalamus and other regions of the brain. In confirmation of previous findings by others CO2 at 10 or 15% was found to elevate both dopa accumulation after dopa decarboxylase inhibition and norepinephrine utilization after tyrosine hydroxylase inhibition. These effects however were found to be transient occurring only during the first 30 min of 2.5 h exposure. In this regard CO2 differs from another form of stress, restraint which produces a sustained 2.5 h increase of dopa accumulation and NE accumulation. Restraint was also more effective than CO2 in depleting endogenous stores of hypothalamic NE. The factor responsible for the adaptation of the catecholamine response to CO2 was not identified although it was shown not to be hypothermia and it was reversed by a 2 h CO2-free recovery period.

  4. Effect of α-bungarotoxin and etorphine on acetylcholine-evoked release of endogenous and radiolabeled catecholamines from primary culture of adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Kageyama, H.; Guidotti, A.

    1984-01-01

    Cell cultures of adrenal medulla have become an important research tool to study basic processes that regulate catecholamine storage, release and synthesis. Release has been studied either by labeling with [ 3 H]norepinephrine and measuring release of radioactivity or by measuring the endogenous catecholamines released with HPLC. Acetylcholine (5X10 -6 -10 -4 M) appears to release preferentially norepinephrine, although the cells store more epinephrine than norepinephrine. Etorphine and α-bungarotoxin antagonize the release of catecholamines elicited by acetylcholine. This inhibitory action appears to be greater when the measurement of endogenous catecholamines rather than radioactive norepinephrine is used to monitor the action of acetylcholine. The data suggest that the measurement of endogenous catecholamines by HPLC is preferable to the [ 3 H]NE loading and release technique, especially when analyzing the effects of low concentrations of drugs that are thought to affect nicotinic receptor function. (Auth.)

  5. Depletion of rat cortical norepinephrine and the inhibition of [3H]norepinephrine uptake by xylamine does not require monoamine oxidase activity

    International Nuclear Information System (INIS)

    Dudley, M.W.

    1988-01-01

    Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline or the pro-drug MDL 72,394 did not block the amine-depleting action of xylamine. Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl, prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974, a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not prevent cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of [ 3 H]norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine

  6. Poincaré plot width, morning urine norepinephrine levels, and autonomic imbalance in children with obstructive sleep apnea.

    Science.gov (United States)

    Chaidas, Konstantinos; Tsaoussoglou, Marina; Theodorou, Emmanouel; Lianou, Loukia; Chrousos, George; Kaditis, Athanasios G

    2014-08-01

    Obstructive sleep apnea (OSA) in childhood is accompanied by sympathetic overflow unopposed by the parasympathetic tone. Complex methods like power spectral analysis of heart rate variability have been applied to study this imbalance. In this report, width of Poincaré scattergram of the R-R interval (parasympathetic tone) and morning urine norepinephrine concentration (sympathetic activity) were used to assess autonomic imbalance. Poincaré plot was obtained from the electrocardiographic channel of nocturnal polysomnography and its width was measured, and norepinephrine-to-creatinine concentration ratio was calculated in morning urine specimen. Twenty children with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia (oxygen saturation of hemoglobin [SpO(2)] nadir plot width (318.7 ± 139.3 ms) and higher ln-transformed urine norepinephrine-to-creatinine ratio (4.5 ± 0.6) than control subjects (484.2 ± 104.4 ms and 3.8 ± 0.4, respectively; P plot width (P = 0.02). Subjects with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia have enhanced sympathetic activity and reduced parasympathetic drive. Poincaré plot width and urine norepinephrine levels are simple measures of autonomic imbalance in pediatric obstructive sleep apnea. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Brush, J.E. Jr.; Eisenhofer, G.; Garty, M.; Stull, R.; Maron, B.J.; Cannon, R.O. III; Panza, J.A.; Epstein, S.E.; Goldstein, D.S.

    1989-01-01

    We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake of norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 +/- 17% in the patients with HCM, significantly less than in the control subjects (79 +/- 13%, p less than 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 +/- 23% versus 13 +/- 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 +/- 77 versus 13 +/- 50 pg/ml, p less than 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 +/- 7.3 versus 0.8 +/- 3.0 ng/min, p less than 0.05)

  8. Radioenzymatic paper-chromatographic assay for dopamine and norepinephrine in cerebroventricular cisternal perfusate of cat following administration of cocaine or d-amphetamine

    International Nuclear Information System (INIS)

    Chiueh, C.C.; Kopin, I.J.

    1978-01-01

    A sensitive radioenzymatic paper chromatographic method was used to measure the endogenous dopamine and norepinephrine content of cerebroventricular cisternal perfusate from cats to provide direct evidence for the catecholamine releasing action of cocaine from brain in vivo. Although relatively less potent than d-emphetamine, cocaine was shown to release endogenous catechloramines, mainly dopamine from the brain. This similarity may be the neurochemical basis for their similar behavioral effects. (U.K.)

  9. Radioenzymatic paper-chromatographic assay for dopamine and norepinephrine in cerebroventricular cisternal perfusate of cat following administration of cocaine or d-amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Chiueh, C C; Kopin, I J [National Inst. of Mental Health, Bethesda, MD (USA)

    1978-08-01

    A sensitive radioenzymatic paper chromatographic method was used to measure the endogenous dopamine and norepinephrine content of cerebroventricular cisternal perfusate from cats to provide direct evidence for the catecholamine releasing action of cocaine from brain in vivo. Although relatively less potent than d-emphetamine, cocaine was shown to release endogenous catechloramines, mainly dopamine from the brain. This similarity may be the neurochemical basis for their similar behavioral effects.

  10. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    NARCIS (Netherlands)

    Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; van der Hart, Marieke; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

    2012-01-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood

  11. Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion.

    Science.gov (United States)

    Ross, Jennifer A; Reyes, Beverly A S; Thomas, Steven A; Van Bockstaele, Elisabeth J

    2018-01-01

    The locus coeruleus (LC)-norepinephrine (NE) system is an understudied circuit in the context of Alzheimer's disease (AD), and is thought to play an important role in neurodegenerative and neuropsychiatric diseases involving catecholamine neurotransmitters. Understanding the expression and distribution of the amyloid beta (Aβ) peptide, a primary component of AD, under basal conditions and under conditions of NE perturbation within the coeruleo-cortical pathway may be important for understanding its putative role in pathological states. Thus, the goal of this study is to define expression levels and the subcellular distribution of endogenous Aβ with respect to noradrenergic profiles in the rodent LC and medial prefrontal cortex (mPFC) and, further, to determine the functional relevance of NE in modulating endogenous Aβ 42 levels. We report that endogenous Aβ 42 is localized to tyrosine hydroxylase (TH) immunoreactive somatodendritic profiles of the LC and dopamine-β-hydroxylase (DβH) immunoreactive axon terminals of the infralimbic mPFC (ILmPFC). Male and female naïve rats have similar levels of amyloid precursor protein (APP) cleavage products demonstrated by western blot, as well as similar levels of endogenous Aβ 42 as determined by enzyme-linked immunosorbent assay. Two models of NE depletion, DSP-4 lesion and DβH knockout (KO) mice, were used to assess the functional relevance of NE on endogenous Aβ 42 levels. DSP-4 lesioned rats and DβH-KO mice show significantly lower levels of endogenous Aβ 42 . Noradrenergic depletion did not change APP-cleavage products resulting from β-secretase processing. Thus, resultant decreases in endogenous Aβ 42 may be due to decreased neuronal activity of noradrenergic neurons, or, by decreased stimulation of adrenergic receptors which are known to contribute to Aβ 42 production by enhancing γ-secretase processing under normal physiological conditions.

  12. Elevated blood plasma levels of epinephrine, norepinephrine, tyrosine hydroxylase, TGFβ1, and TNFα associated with high-altitude pulmonary edema in Indian population

    Directory of Open Access Journals (Sweden)

    Pandey P

    2016-08-01

    Full Text Available Priyanka Pandey,1,2 Zahara Ali,1,2 Ghulam Mohammad,3 MA Qadar Pasha1,2 1Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 2Department of Biotechnology, Savitribai Phule Pune University, Pune, 3Department of Medicine, SNM Hospital, Ladakh, Jammu and Kashmir, India Abstract: Biomarkers are essential to unravel the locked pathophysiology of any disease. This study investigated the role of biomarkers and their interactions with each other and with the clinical parameters to study the physiology of high-altitude pulmonary edema (HAPE in HAPE-patients (HAPE-p against adapted highlanders (HLs and healthy sojourners, HAPE-controls (HAPE-c. For this, seven circulatory biomarkers, namely, epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor beta 1, tumor necrosis factor alpha (TNFα, platelet-derived growth factor beta beta, and C-reactive protein (CRP, were measured in blood plasma of the three study groups. All the subjects were recruited at ~3,500 m, and clinical features such as arterial oxygen saturation (SaO2, body mass index, and mean arterial pressure were measured. Increased levels of epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor-beta 1, and TNFα were observed in HAPE-p against the healthy groups, HAPE-c, and HLs (P<0.0001. CRP levels were decreased in HAPE-p against HAPE-c and HLs (P<0.0001. There was no significant difference or very marginal difference in the levels of these biomarkers in HAPE-c and HLs (P>0.01. Correlation analysis revealed a negative correlation between epinephrine and norepinephrine (P=4.6E-06 in HAPE-p and positive correlation in HAPE-c (P=0.004 and HLs (P=9.78E-07. A positive correlation was observed between TNFα and CRP (P=0.004 in HAPE-p and a negative correlation in HAPE-c (P=4.6E-06. SaO2 correlated negatively with platelet-derived growth factor beta beta (HAPE-p; P=0.05, norepinephrine (P=0.01, and TNFα (P=0.005 and

  13. Plasma levels of norepinephrine during the periovulatory period in normal women

    International Nuclear Information System (INIS)

    Badano, A.R.; Nagle, C.A.; Casas, P.R.F.; Miechi, H.; Mirkin, A.; Turner, D.E.; Aparicio, N.; Rosner, J.M.

    1978-01-01

    Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E 2 ), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E 2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E 2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E 2 peak. These values remained high until 16 hours before the LH peak and decreased gradully, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge

  14. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

    Science.gov (United States)

    Serotonin and norepinephrine reuptake inhibitors (SNRIs) Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, ... effects they may cause. By Mayo Clinic Staff Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class ...

  15. Endogenous heparin levels in the controlled asthmatic patient ...

    African Journals Online (AJOL)

    Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

  16. Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish.

    Science.gov (United States)

    Singh, Chanpreet; Oikonomou, Grigorios; Prober, David A

    2015-09-16

    Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine β-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep, dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons.

  17. Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

    Science.gov (United States)

    Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

    2014-09-01

    We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase

    NARCIS (Netherlands)

    Warren, C.M.; van den Brink, R.L.; Nieuwenhuis, S.; Bosch, J.A.

    It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy

  19. Norepinephrine storage, distribution, and release in diabetic cardiomyopathy

    International Nuclear Information System (INIS)

    Ganguly, P.K.; Beamish, R.E.; Dhalla, K.S.; Innes, J.R.; Dhalla, N.S.

    1987-01-01

    The ability of hearts to store, distribute, and release norepinephrine (NE) was investigated in rats 8 wk after the induction of diabetes by an injection of streptozotocin. Chronic diabetes was associated with increased content and concentration of NE in heart and in other tissues such as kidney, brain, and spleen. Reserpine or tyramine treatment resulted in depletion of endogenous cardiac NE in control and diabetic rats. The depletion of NE stores at different times after a dose of reserpine was greater in diabetic hearts. On the other hand, NE stores in diabetic hearts were less sensitive than control hearts to low doses of tyramine but were more sensitive to high doses. The uptake of [ 3 H]NE was greater in diabetic hearts in isolated perfused preparations. In comparison with the control values, diabetic hearts showed a decrease in [ 3 H]NE in the granular fraction and an increase in the supernatant fraction. Diabetic hearts also showed an accelerated spontaneous release of [ 3 H]NE. The increased cardiac NE and the uptake and release of NE in diabetic animals were reversible upon treatment with insulin. These results are consistent with the view that sympathetic activity is increased in diabetic cardiomyopathy and indicate that cardiac NE in diabetic rats is maintained at a higher level partly due to an increased uptake of released NE by adrenergic nerve terminals

  20. Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

    1982-06-22

    The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

  1. Relationships of Whole Blood Serotonin and Plasma Norepinephrine within Families.

    Science.gov (United States)

    Leventhal, Bennett L.; And Others

    1990-01-01

    This study of 47 families of autistic probands found that whole blood serotonin was positively correlated between autistic children and their mothers, fathers, and siblings, but plasma norepinephrine levels were not. (Author/JDD)

  2. Norepinephrine remains increased in the six-minute walking test after heart transplantation

    Directory of Open Access Journals (Sweden)

    Guilherme Veiga Guimarães

    2010-01-01

    Full Text Available OBJECTIVE: We sought to evaluate the neurohormonal activity in heart transplant recipients and compare it with that in heart failure patients and healthy subjects during rest and just after a 6-minute walking test. INTRODUCTION: Despite the improvements in quality of life and survival provided by heart transplantation, the neurohormonal profile is poorly described. METHODS: Twenty heart transplantation (18 men, 49±11 years and 8.5±3.3 years after transplantation, 11 heart failure (8 men, 43±10 years, and 7 healthy subjects (5 men 39±8 years were included in this study. Blood samples were collected immediately before and during the last minute of the exercise. RESULTS: During rest, patients' norepinephrine plasma level (659±225 pg/mL was higher in heart transplant recipients (463±167 pg/mL and heathy subjects (512±132, p<0.05. Heart transplant recipient's norepinephrine plasma level was not different than that of healthy subjects. Just after the 6-minute walking test, the heart transplant recipient's norepinephrine plasma level (1248±692 pg/mL was not different from that of heart failure patients (1174±653 pg/mL. Both these groups had a higher level than healthy subjects had (545±95 pg/mL, p<0.05. CONCLUSION: Neurohormonal activity remains increased after the 6-minute walking test after heart transplantation.

  3. Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830

    Directory of Open Access Journals (Sweden)

    Casanova Jose-Miguel

    2002-01-01

    Full Text Available Abstract Background Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain. Methods Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups; 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS. Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores. Results Norepinephrine-evoked pain was seen in 80 % of FM patients (95% confidence intervals 56.3 – 94.3%, in 30 % of rheumatoid arthritis patients and in 30 % of healthy controls (95% confidence intervals 11.9 – 54.3 (p Conclusions Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome.

  4. Relationship between Personality Traits and Endogenous Analgesia: The Role of Harm Avoidance.

    Science.gov (United States)

    Nahman-Averbuch, Hadas; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena; Granot, Michal

    2016-01-01

    Whether psychological factors such as anxiety and pain catastrophizing levels influence the expression of endogenous analgesia in general and, more specifically, the conditioned pain modulation (CPM) response is still under debate. It may be assumed that other psychological characteristics also play a role in the CPM response. The neurotransmitters serotonin, dopamine, and norepinephrine are involved both in CPM, as well as personality traits such as harm avoidance (HA), novelty seeking (NS), and reward dependence (RD), which can be obtained by the Tridimensional Personality Questionnaire (TPQ). However, the associations between these traits (HA, NS, and RD) with endogenous analgesia revealed by CPM have not yet been explored. Healthy middle-age subjects (n = 28) completed the TPQ, Spielberger's State Anxiety Inventory, and the Pain Catastrophizing Scale and were assessed for CPM paradigms using thermal phasic temporal summation as the "test stimulus" and hand immersion into hot water bath (CPM water) or contact heat (CPM contact) for "conditioning stimulus." Higher levels of HA were associated with less-efficient CPM responses obtained by both paradigms: CPM water (r = 0.418, P = 0.027) and CPM contact (r = 0.374, P = 0.050). However, NS and RD were not associated with the other measurements. No significant relationship was observed between state anxiety and pain catastrophizing levels and the CPM responses. The relationship between the capacity of endogenous analgesia and the tendency to avoid aversive experience can be explained by mutual mechanisms involving similar neurotransmitters or brain areas. These findings illuminate the key role of harm avoidance obtained by the TPQ in determining the characteristics of pain modulation profile. © 2014 World Institute of Pain.

  5. Norepinephrine metabolism in man using deuterium labeling: turnover 4-hydroxy-3-methoxymandelic acid

    Energy Technology Data Exchange (ETDEWEB)

    Mardh, G.; Sjoequist, B.; Anggard, E.

    1982-06-01

    4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) labeled with three deuterium atoms was used to study the turnover and fate of HMMA following intravenous injection. Five healthy men were given a pulse dose of 5.0 mumol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 +/- 10% (mean +/- SD). No conversion of HMMA to 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 +/- 0.22 h. The apparent volume of distribution was 0.36 +/- 0.11 L/kg. The production rate or body turnover was 1.27 +/- 0.51 mumol HMMA/h and urinary excretion rate was 0.82 +/- 0.22 mumol/h. These results show that HMMA is turnover over rapidly in a relatively small volume of distribution and that, unlike HMPG, it is an end metabolite of norepinephrine in man.

  6. Alteration effect of the PGFsub(2α) inhibition on the 3H-norepinephrine release caused by α2 receptor blocking, sodium loading and 4-aminopyridine addition in isolated pulmonary arteries of rabbit

    International Nuclear Information System (INIS)

    Bunyevacs, Zs.; Toeroek, T.; Hadhazy, P.; Magyar, K.; Feher, L.; Vizi, E.Sz.

    1983-01-01

    The tritium labelled norepinephrine release was measured in isolated pulmonary artery of rabbit. If the 3 H-norepinephrine release was induced by nerves stimulated with electric current, the PGFsub(2α) inhibited the release by 62%. In the presence of Yohimbin the inhibitory effect of FGFsub(2α) was increased to 78.8%. If the Na + pump activity was reduced by potassium-free medium the PGFsub(2α) inhibition remained at 62%. In the presence of 4-aminopyridine the potassium channel was blocked and the PGFsub(2α) inhibition decreased to 32.1%. The endogen prostaglandin may serve as a modulator of the neurotransmitter release. (L.G.)

  7. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

    The serotonin transporter (SERT) and the norepinephrine transporter (NET) are sodium-dependent neurotransmitter transporters responsible for reuptake of released serotonin and norepinephrine, respectively, into nerve terminals in the brain. A wide range of inhibitors of SERT and NET are used...

  8. Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

    Science.gov (United States)

    Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

    2016-05-04

    DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation.

    Science.gov (United States)

    Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E

    2015-07-01

    It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

  10. Norepinephrine turnover in brown adipose tissue is stimulated by a single meal

    International Nuclear Information System (INIS)

    Glick, Z.; Raum, W.J.

    1986-01-01

    A single meal stimulates brown adipose tissue (BAT) thermogenesis in rats. In the present study the role of norepinephrine in this thermogenic response was assessed from the rate of its turnover in BAT after a single test meal. For comparison, norepinephrine turnover was determined in the heart and spleen. A total of 48 male Wistar rats (200 g) were trained to eat during two feeding sessions per day. On the experimental day, one group (n = 24) was meal deprived and the other (n = 24) was given a low-protein high-carbohydrate test meal for 2 h. The synthesis inhibition method with α-methyl-p-tyrosine was employed to determine norepinephrine turnover from its concentration at four hourly time points after the meal. Tissue concentrations of norepinephrine were determined by radioimmunoassay. Norepinephrine concentration and turnover rate were increased more than threefold in BAT of the meal-fed compared with the meal-deprived rats. Neither were significantly altered by the meal in the heart or spleen. The data suggest that norepinephrine mediates a portion of the thermic effect of meals that originate in BAT

  11. Relative contributions of norepinephrine and serotonin transporters to antinociceptive synergy between monoamine reuptake inhibitors and morphine in the rat formalin model.

    Directory of Open Access Journals (Sweden)

    Fei Shen

    Full Text Available Multimodal analgesia is designed to optimize pain relief by coadministering drugs with distinct mechanisms of action or by combining multiple pharmacologies within a single molecule. In clinical settings, combinations of monoamine reuptake inhibitors and opioid receptor agonists have been explored and one currently available analgesic, tapentadol, functions as both a µ-opioid receptor agonist and a norepinephrine transporter inhibitor. However, it is unclear whether the combination of selective norepinephrine reuptake inhibition and µ-receptor agonism achieves an optimal antinociceptive synergy. In this study, we assessed the pharmacodynamic interactions between morphine and monoamine reuptake inhibitors that possess different affinities and selectivities for norepinephrine and serotonin transporters. Using the rat formalin model, in conjunction with measurements of ex vivo transporter occupancy, we show that neither the norepinephrine-selective inhibitor, esreboxetine, nor the serotonin-selective reuptake inhibitor, fluoxetine, produce antinociceptive synergy with morphine. Atomoxetine, a monoamine reuptake inhibitor that achieves higher levels of norepinephrine than serotonin transporter occupancy, exhibited robust antinociceptive synergy with morphine. Similarly, a fixed-dose combination of esreboxetine and fluoxetine which achieves comparable levels of transporter occupancy potentiated the antinociceptive response to morphine. By contrast, duloxetine, a monoamine reuptake inhibitor that achieves higher serotonin than norepinephrine transporter occupancy, failed to potentiate the antinociceptive response to morphine. However, when duloxetine was coadministered with the 5-HT3 receptor antagonist, ondansetron, potentiation of the antinociceptive response to morphine was revealed. These results support the notion that inhibition of both serotonin and norepinephrine transporters is required for monoamine reuptake inhibitor and opioid

  12. Continuous infusion of tracer norepinephrine may miscalculate unidirectional nerve uptake of norepinephrine in humans

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Christensen, N J; Ring-Larsen, H

    1989-01-01

    In order to evaluate uptake kinetics of norepinephrine (NE) in different tissues, a catheterization study was performed in control subjects (n = 6) and patients with enhanced sympathetic nervous activity (cirrhosis, n = 12) during constant intravenous infusion of L[3H]norepinephrine ([3H]NE) for 75...... minutes. In spite of a higher NE spillover from kidneys in patients compared with controls (82 vs. 49 ng/min, p less than 0.01), renal extraction ratios of [3H]NE were similar in the two groups (0.33 vs. 0.32, NS), and no significant change was observed during the time of infusion. In contrast, liver......-intestine extraction ratios of [3H]NE decreased significantly and equally with infusion time in patients (from 0.57 to 0.44, p less than 0.01) and controls (from 0.59 to 0.46, p less than 0.01). This was observed despite the fact that spillover of NE from this vascular bed was observed only in patients with cirrhosis...

  13. Norepinephrine kinetics and dynamics in septic shock and trauma patients.

    Science.gov (United States)

    Beloeil, H; Mazoit, J-X; Benhamou, D; Duranteau, J

    2005-12-01

    There is considerable variability in the inter-patient response to norepinephrine. Pharmacokinetic studies of dopamine infusion in volunteers and in patients have also shown large variability. The purpose of this study was to define the pharmacokinetics of norepinephrine in septic shock and trauma patients. After Ethical Committee approval and written informed family consent, 12 patients with septic shock and 11 trauma patients requiring norepinephrine infusion were studied. Norepinephrine dose was increased in three successive steps of 0.1 mg kg(-1) min(-1) at 15-min intervals (20% maximum allowed increase in arterial pressure). Arterial blood was sampled before and at 0.5, 13, and 15 min after each infusion rate change and 30 s, 1, 2, 5, 10, and 15 min after return to baseline dosing. Norepinephrine was assayed by HPLC. The pharmacokinetics were modelled using NONMEM (one-compartment model). The effects of group, body weight (BW), gender and SAPS II (Simplified Acute Physiology Score II) [Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. J Am Med Assoc 1993; 270: 2957-63] patients score on clearance (CL) and volume of distribution (V) were tested. Group, gender, and BW did not influence CL or V. CL was negatively related to SAPS II. CL and T(1/2) varied from 3 litre min(-1) and 2 min, respectively, when SAPS II=20 to 0.9 litre min(-1) and 6.8 min when SAPS II=60. In trauma patients and in septic shock patients, norepinephrine clearance is negatively related to SAPS II.

  14. Norepinephrine release in arteries of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Zsoter, T.T.; Wolchinsky, C.; Lawrin, M.; Sirko, S.

    1982-01-01

    The role of the sympathetic nervous system in arterial hypertension cannot be properly evaluated until it is known about the activity in the vessels themselves. In this study researchers investigated the effect of transmural stimulation on the tail artery - labelled in vitro with 3 H-norepinephrine - of 7-9 week old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKR). Electrical stimulation using two frequencies (2 and 10 Hz) resulted in significantly more 3 H overflow in vessels from SHR than from WKR. With 10 Hz stimulation the fractional release was also greater. Column chromatographic analysis of 3 H overflow revealed that transmural stimulation in arteries of SHR enhanced mainly the release of norepinephrine and not of its metabolites. Significantly, an increased release of 3 H-norepinephrine on stimulation was observed in SHR before the full development of hypertension suggesting that it might be a cause rather than a consequence of high blood pressure

  15. Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2014-01-01

    Full Text Available Background. During hypertensive therapy for post-subarachnoid hemorrhage (SAH symptomatic vasospasm, norepinephrine is commonly used to reach target blood pressures. Concerns over aggravation of vasospasm with norepinephrine exist. Objective. To describe norepinephrine temporally related deterioration in neurological examination of two post-SAH patients in vasospasm. Methods. We retrospectively reviewed two charts of patients with delayed cerebral ischemia (DCI post-SAH who deteriorated with norepinephrine infusions. Results. We identified two patients with DCI post-SAH who deteriorated during hypertensive therapy with norepinephrine. The first, a 43-year-old male presented to hospital with DCI, failed MABP directed therapy with rapid deterioration in exam with high dose norepinephrine and MABP of 140–150 mm Hg. His exam improved on continuous milrinone and discontinuation of norepinephrine. The second, a 39-year-old female who developed DCI on postbleed day 8 responded to milrinone therapy upfront. During further deterioration and after angioplasty, norepinephrine was utilized to drive MABP to 130–140 mm Hg. Progressive deterioration in examination occurred after angioplasty as norepinephrine doses escalated. After discontinuation of norepinephrine and continuation of milrinone, function dramatically returned but not to baseline. Conclusions. The potential exists for worsening of DCI post-SAH with hypertensive therapy directed by norepinephrine. A potential role exists for vasodilation and inotropic directed therapy with milrinone in the setting of DCI post-SAH.

  16. Synthesis and structure-distribution study of radioiodinated norepinephrine storage analogs

    Energy Technology Data Exchange (ETDEWEB)

    Wieland, D.M.; Inbasekaran, M.; Brown, L.E.; Marsh, D.D.; Beierwaltes, W.H. (Michigan Univ., Ann Arbor (USA). Medical Center)

    Unlabelled analogs of norepinephrine have been synthesised and then labelled with /sup 125/I in an attempt to find an agent with heart uptake and neuronal specificity greater than metaiodobenzylguanidine (MIBG). The analogs of norepinephrine were injected intravenously into dogs and showed a heart concentration similar to MIBG. Neuronal specificity of some analogs is being evaluated in rat heart.

  17. Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation.

    Science.gov (United States)

    Ordway, Gregory A; Jia, Weihong; Li, Jing; Zhu, Meng-Yang; Mandela, Prashant; Pan, Jun

    2005-04-30

    Previous research has shown that exposure of norepinephrine transporter (NET)-expressing cells to desipramine (DMI) downregulates the norepinephrine transporter, although changes in the several transporter parameters do not demonstrate the same time course. Exposures to desipramine for effects of residual desipramine on norepinephrine transporter binding and uptake were re-evaluated following exposures of PC12 cells to desipramine using different methods to remove residual drug. Using a method that minimizes residual drug, exposure of intact PC12 cells to desipramine for 4h had no effect on uptake capacity or [(3)H]nisoxetine binding to the norepinephrine transporter, while exposures for > or =16 h reduced uptake capacity. Desipramine-induced reductions in binding to the transporter required >24 h or greater periods of desipramine exposure. This study confirms that uptake capacity of the norepinephrine transporter is reduced earlier than changes in radioligand binding, but with a different time course than originally shown. Special pre-incubation procedures are required to abolish effects of residual transporter inhibitor when studying inhibitor-induced transporter regulation.

  18. Synthesis and structure-distribution study of radioiodinated norepinephrine storage analogs

    International Nuclear Information System (INIS)

    Wieland, D.M.; Inbasekaran, M.; Brown, L.E.; Marsh, D.D.; Beierwaltes, W.H.

    1982-01-01

    Unlabelled analogs of norepinephrine have been synthesised and then labelled with 125 I in an attempt to find an agent with heart uptake and neuronal specificity greater than metaiodobenzylguanidine (MIBG). The analogs of norepinephrine were injected intravenously into dogs and showed a heart concentration similar to MIBG. Neuronal specificity of some analogs is being evaluated in rat heart. (U.K.)

  19. Norepinephrine kinetics during insulin-induced hypoglycemia

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Larsen, S

    1985-01-01

    Norepinephrine (NE) kinetics (plasma appearance rate, clearance, and forearm extraction) were measured during insulin-induced hypoglycemia in six healthy subjects. NE clearance did not change during hypoglycemia, indicating that the increase in plasma NE during hypoglycemia is due to an increased...

  20. Dopamine versus norepinephrine in the treatment of cardiogenic shock: A PRISMA-compliant meta-analysis.

    Science.gov (United States)

    Rui, Qing; Jiang, Yufeng; Chen, Min; Zhang, Nannan; Yang, Huajia; Zhou, Yafeng

    2017-10-01

    Guidelines recommend that norepinephrine (NA) should be used to reach the target mean arterial pressure (MAP) during cardiogenic shock (CS), rather than epinephrine and dopamine (DA). However, there has actually been few studies on comparing norepinephrine with dopamine and their results conflicts. These studies raise a heat discussion. This study aimed to validate the effectiveness of norepinephrine for treating CS in comparison with dopamine. We performed a meta-analysis of randomized controlled trials (RCTs) to assess pooled estimates of risk ratio (RR) and 95% confidence interval (CI) for 28-day mortality, incidence of arrhythmic events, gastrointestinal reaction, and some indexes after treatment. Compared with dopamine, patients receiving norepinephrine had a lower 28-day mortality (RR 1.611 [95% CI 1.219-2.129]; P dopamine in 2 subgroups. Our analysis revealed that norepinephrine was associated with a lower 28-day mortality, a lower risk of arrhythmic events, and gastrointestinal reaction. No matter whether CS is caused by coronary heart disease or not, norepinephrine is superior to dopamine for correcting CS on the 28-day mortality.

  1. Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

    Science.gov (United States)

    Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly As; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2013-09-01

    Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.

  2. Pavlovian autoshaping procedures increase plasma corticosterone and levels of norepinephrine and serotonin in prefrontal cortex in rats.

    Science.gov (United States)

    Tomie, Arthur; Tirado, Aidaluz D; Yu, Lung; Pohorecky, Larissa A

    2004-08-12

    Pavlovian autoshaping procedures provide for pairings of a small object conditioned stimulus (CS) with a rewarding substance unconditioned stimulus (US), resulting in the acquisition of complex sequences of CS-directed skeletal-motor responses or autoshaping conditioned responses (CRs). Autoshaping procedures induce higher post-session levels of corticosterone than in controls receiving CS and US randomly, and the enhanced post-session corticosterone levels have been attributed to the appetitive or arousal-inducing effects of autoshaping procedures. Enhanced corticosterone release can be induced by aversive stimulation or stressful situations, where it is often accompanied by higher levels of norepinephrine (NE) and serotonin (5-HT) in prefrontal cortex (PFC) but not in striatum (ST). Effects of autoshaping procedures on post-session corticosterone levels, NE contents in PFC, and 5-HT contents in PFC and ST were investigated in male Long-Evans rats. Post-session blood samples revealed higher corticosterone levels in the CS-US Paired group (n = 46) than in the CS-US Random control group (n = 21), and brain samples revealed higher levels of PFC NE and 5-HT in CS-US Paired group. Striatal 5-HT levels were unaltered by the autoshaping procedures. Autoshaping procedures provide for appetitive stimulation and induce an arousal-like state, as well as simultaneous stress-like changes in plasma corticosterone and monoamine levels in PFC. Autoshaping, therefore, may be useful for the study of endocrine and central processes associated with appetitive conditions.

  3. Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects?

    DEFF Research Database (Denmark)

    Brassard, P.; Seifert, T.; Secher, Niels H.

    2009-01-01

    BACKGROUND: Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion of norep......BACKGROUND: Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion...... of norepinephrine on cerebral oxygenation in healthy subjects. METHODS: Three doses of norepinephrine (0.05, 0.1, and 0.15 microg kg(-1) min(-1) for 20 min each) were infused in nine healthy subjects [six males; 26 (6) yr, mean (SD)]. MAP, cerebral oxygenation characterized by frontal lobe oxygenation (Sc(O2...

  4. Investigation of the connection between the quality of protein, protein level and endogenous N excretion

    International Nuclear Information System (INIS)

    Koehler, R.; Gebhardt, G.

    1979-01-01

    The influence of various protein qualities as well as of different levels of protein on the amount of endogenous N excretion, metabolic fecal nitrogen (MFN) and endogenous urinary N (EUN) was determined in growing albino rats. The test rations were labelled with admixtures of 15 N-DL-methionine and 15 N-DL-lysine, respectively, or contained feed protein enriched with 15 N. EUN and MFN and their sum (the N maintenance requirement) showed the influence of the respective protein source and its dependence on the protein level. The endogenous N excretions showed an opposite tendency to the N balance; for high-quality protein feedstuffs with a high N balance (e.g. dried eggs) they are lower than for protein sources of inferior quality, with a low N-balance only (e.g. wheat gluten). Presumably this interaction of retention and maintenance is due to the complementary effect of exogenous and endogenous amino acids in the N and amino acid pool, respectively. Provided that the N dose and the live weight of the animals are comparable, the N balance appears to be more suitable as parameter for the description of the protein quality and the calculation of the protein utilisation than N retention, as the sum of N balance and the values of MFN and EUN (depending on the feedstuffs and the N level). (author)

  5. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies

    NARCIS (Netherlands)

    Ruhe, H. G.; Mason, N. S.; Schene, A. H.

    2007-01-01

    Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). Monoamine depletion studies investigate the direct effects of monoamines on mood. Acute tryptophan depletion (ATD) or para-chlorophenylalanine

  6. Inhibition of the norepinephrine transporter by χ-conotoxin dendrimers.

    Science.gov (United States)

    Wan, Jingjing; Brust, Andreas; Bhola, Rebecca F; Jha, Prerna; Mobli, Mehdi; Lewis, Richard J; Christie, Macdonald J; Alewood, Paul F

    2016-05-01

    Peptide dendrimers are a novel class of macromolecules of emerging interest with the potential of delayed renal clearance due to their molecular size and enhanced activity due to the multivalency effect. In this work, an active analogue of the disulfide-rich χ-conotoxin χ-MrIA (χ-MrIA), a norepinephrine reuptake (norepinephrine transporter) inhibitor, was grafted onto a polylysine dendron. Dendron decoration was achieved by employing copper-catalyzed alkyne-azide cycloaddition with azido-PEG chain-modified χ-MrIA analogues, leading to homogenous 4-mer and 8-mer χ-MrIA dendrimers with molecular weights ranging from 8 to 22 kDa. These dendrimers were investigated for their impact on peptide secondary structure, in vitro functional activity, and potential anti-allodynia in vivo. NMR studies showed that the χ-MrIA tertiary structure was maintained in the χ-MrIA dendrimers. In a functional norepinephrine transporter reuptake assay, χ-MrIA dendrimers showed slightly increased potency relative to the azido-PEGylated χ-MrIA analogues with similar potency to the parent peptide. In contrast to χ-MrIA, no anti-allodynic action was observed when the χ-MrIA dendrimers were administered intrathecally in a rat model of neuropathic pain, suggesting that the larger dendrimer structures are unable to diffuse through the spinal column tissue and reach the norepinephrine transporter. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  7. ENDOGENOUS OR EXOGENOUS INNOVATION DEVELOPMENT IN INDUSTRY ON REGIONAL LEVEL?

    Directory of Open Access Journals (Sweden)

    Arkadiusz Świadek

    2014-04-01

    Full Text Available At the moment endogenous growth theory has become increasingly popular in the world of science, particularly in developed countries. This article aims to show, for two regions case, the needs and sense of applying this theory in the polish regions. Due to the low level of economic development of many Polish regions, they are unable to growth in a comparable rate as regions in developed countries. This explains the economic divergence between polish regions and the highly developed regions of Europe and the World. Stimulating economic growth is insufficient in such cases, because of the weakness of its internal factors. Therefore it is important to strengthen an external impact to keep internal development. It means that the endogenous growth theory is no reason to exist, in conditions of poor polish regions. Without external inputs there can’t be convergences processes. Therefore, the economic development of the Polish regions should be based on the exogenous growth theory.

  8. Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects?

    DEFF Research Database (Denmark)

    Brassard, P.; Seifert, T.; Secher, Niels H.

    2009-01-01

    BACKGROUND: Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion of norep......BACKGROUND: Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion...... of norepinephrine on cerebral oxygenation in healthy subjects. METHODS: Three doses of norepinephrine (0.05, 0.1, and 0.15 microg kg(-1) min(-1) for 20 min each) were infused in nine healthy subjects [six males; 26 (6) yr, mean (SD)]. MAP, cerebral oxygenation characterized by frontal lobe oxygenation (Sc(O2...... infused at 0.1 microg kg(-1) min(-1) [Sc(O2): 78 (75-94) to 69 (61-83)%; P

  9. Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

    International Nuclear Information System (INIS)

    Farde, L.; Halldin, C.; Naagren, K.; Suhara, Tetsuya; Karlsson, P.; Schoeps, K.O.; Swahn, C.G.; Bone, D.

    1994-01-01

    (-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [ 11 C]norepinephrine indicates that enatiomerically pure(-)-[ 11 C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

  10. Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

    Energy Technology Data Exchange (ETDEWEB)

    Farde, L [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Halldin, C [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Naagren, K [Turku Univ., Cyclotron/PET Center (Finland); Suhara, Tetsuya [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Karlsson, P [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Schoeps, K O [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Swahn, C G [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Bone, D [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden)

    1994-04-01

    (-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [[sup 11]C]norepinephrine indicates that enatiomerically pure(-)-[[sup 11]C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

  11. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Directory of Open Access Journals (Sweden)

    Shohei Ogata

    Full Text Available Although intravenous immunoglobulin (IVIG is highly effective in Kawasaki disease (KD, mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I, the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG.We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (sST6Gal-I levels were measured by ELISA.There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively.Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  12. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

    NARCIS (Netherlands)

    Dubin, Arnaldo; Pozo, Mario O.; Casabella, Christian A.; Palizas, Fernando; Murias, Gaston; Moseinco, Miriam C.; Kanoore Edul, Vanina S.; Estenssoro, Elisa; Ince, Can

    2009-01-01

    Introduction Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were

  13. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Science.gov (United States)

    Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

    2013-01-01

    Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  14. Urinary endogenous sex hormone levels and the risk of postmenopausal breast cancer

    NARCIS (Netherlands)

    Onland-Moret, N.C.; Kaaks, R.; Noord, P.A.H. van; Rinaldi, S.; Key, T.; Grobbee, D.E.; Peeters, P.H.M.

    2003-01-01

    To assess the relation between urinary endogenous sex steroid levels and the risk of postmenopausal breast cancer, a nested case–cohort study was conducted within a large cohort (the DOM cohort) in the Netherlands (n¼9 349). Until the end of follow-up (1 January 1996), 397 postmenopausal breast

  15. The Design, Synthesis and Structure-Activity Relationship of Mixed Serotonin, Norepinephrine and Dopamine Uptake Inhibitors

    Science.gov (United States)

    Chen, Zhengming; Yang, Ji; Skolnick, Phil

    The evolution of antidepressants over the past four decades has involved the replacement of drugs with a multiplicity of effects (e.g., TCAs) by those with selective actions (i.e., SSRIs). This strategy was employed to reduce the adverse effects of TCAs, largely by eliminating interactions with certain neurotransmitters or receptors. Although these more selective compounds may be better tolerated by patients, selective drugs, specifically SSRIs, are not superior to older drugs in treating depressed patients as measured by response and remission rates. It may be an advantage to increase synaptic levels of both serotonin and norepinephrine, as in the case of dual uptake inhibitors like duloxetine and venlafaxine. An important recent development has been the emergence of the triple-uptake inhibitors (TUIs/SNDRIs), which inhibit the uptake of the three neurotransmitters most closely linked to depression: serotonin, norepinephrine, and dopamine. Preclinical studies and clinical trials indicate that a drug inhibiting the reuptake of all three of these neurotransmitters could produce more rapid onset of action and greater efficacy than traditional antidepressants. This review will detail the medicinal chemistry involved in the design, synthesis and discovery of mixed serotonin, norepinephrine and dopamine transporter uptake inhibitors.

  16. Irradiation induced changes in endogenous regional distribution of catecholamines in rat brain and possible control through combined radioprotective treatments

    International Nuclear Information System (INIS)

    Hassan, S.H.M.; Elsayed, M.E.; Roushdy, H.M.; Maklaad, Y.A.

    1994-01-01

    The present study has been conducted aiming to evaluate the protective role of imidazole serotonin or their combination, on the radiation induced changes in the endogenous catecholamine contents in various areas of rat's brain : cortex, striatum, cerebellum, pons and medulla and thalamus and hypothalamus. Whole body gamma-irradiation (6 Gy) resulted in significant progressive decreases of catecholamine (epinephrine, norepinephrine and dopamine) contents, as investigated one and seven days post exposure. Administration of imidazole or serotonin showed to control radiation induced changes in catecholamine contents. Higher protection with lower potential risk of toxicity could be achieved by administration of lower doses of combined agents. The data suggest that, the endogenous concentration of catecholamines in the brain may play an important role in diagnosing the radiation hazard and evaluating the protective capacity of pharmacologic radioprotective. 2 figs

  17. Combined Norepinephrine / Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression and Oxytocin in the Rat

    Directory of Open Access Journals (Sweden)

    Elizabeth Thomas Cox

    2011-06-01

    Full Text Available BACKGROUND: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior, although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent maternal behavior in rodents indicated significant alterations in postpartum maternal care, aggression and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on maternal behavior, aggression, and oxytocin system changes. METHODS: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. Maternal behavior and postpartum aggression were assessed on postpartum days one and six respectively. Oxytocin levels were measured in relevant brain regions on postpartum day seven. Predictions were that amitriptyline would decrease maternal behavior and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. RESULTS: Amitriptyline and desiprimine differentially reduced maternal behavior, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in

  18. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    Science.gov (United States)

    D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

    2015-01-01

    Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenouslevels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

  19. [Endogenous nociceptin level in ischemic stroke: connection to serotonin system].

    Science.gov (United States)

    Tekes, Kornélia; Hantos, Mónika; Bátor, György; Gyenge, Melinda; Laufer, Rudolf; Folyovich, András

    2006-06-01

    Particular role of the heptadecapeptide nociceptin (orphanin FQ), the endogenous agonist of the NOP receptor, has been widely demonstrated in the regulation of pain sensation and anxiety-related behavior. In our best knowledge this is the first study reporting plasma nociceptin levels in 26 acute stroke and 6 transiens ischemic attack (TIA) patients. We have found significantly elevated plasma nociceptin levels in all the three groups of patients studied (stroke influencing the carotis or the lacunar region and TIA). We suggest that elevated plasma nociceptin level is the consequence of stroke as in the group of patients recovered from previous stroke was found similar the control value. Plasma serotonin level was found non-significantly decreased in patients with stroke influencing the lacunar region and TIA patients. However the plasma 5-hydroxy-indoleacetic acid (5HIAA) levels were found significantly elevated in patient groups with stroke influencing both the carotis and the lacunar regions. Data may serve as further evidence for the serotonergic dysregulation in stroke.

  20. Increasing CNS norepinephrine levels by the precursor L-DOPS facilitates beam-walking recovery after sensorimotor cortex ablation in rats.

    Science.gov (United States)

    Kikuchi, K; Nishino, K; Ohyu, H

    2000-03-31

    The present investigation was conducted to document a role of L-threo-3,4-dihydroxyphenylserine (L-DOPS), precursor of L-norepinephrine (NE), in the functional recovery from beam-walking performance deficits in rats after unilateral sensorimotor cortex ablation. L-DOPS was administered simultaneously with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor), and the regional contents of NE in the cerebral cortex, hippocampus, and cerebellum were assayed. Behavioral recovery was demonstrated by the rats treated with L-DOPS and BSZ, and the rate of recovery was significantly different from that of either BSZ-treated or vehicle-treated control rats. The NE tissue levels in the three discrete regions of the rat brain were significantly elevated in the experimental rats receiving both L-DOPS and BSZ. The present studies indicate that increasing NE levels by the precursor L-DOPS may be responsible for facilitating behavioral recovery from beam-walking performance deficits in rats, and further suggest that L-DOPS may become one of the candidate compounds for further clinical human trials promoting functional recovery after injuries to the cerebral cortex.

  1. Kinetics of the norepinephrine analog [76Br]-meta-bromobenzylguanidine in isolated working rat heart

    International Nuclear Information System (INIS)

    Raffel, David; Loc'h, Christian; Mardon, Karine; Maziere, Bernard; Syrota, Andre

    1998-01-01

    A related set of kinetic studies of the norepinephrine analog [ 76 Br]-meta-bromobenzylguanidine (MBBG) were performed with an isolated working rat heart preparation. A series of constant infusion studies over a wide range of MBBG concentrations allowed estimation of the Michaelis-Menten constants for transport by the neuronal norepinephrine transporter (uptake 1 ) and the extraneuronal uptake system (uptake 2 ). Pharmacological blocking studies with inhibitors of uptake 1 , uptake 2 and vesicular uptake were performed to delineate the relative importance of these norepinephrine handling mechanisms on the kinetics of MBBG in the rat heart. Bolus injection studies were done to assess the ability of compartmental modeling techniques to characterize the kinetics of MBBG. These studies demonstrate that MBBG shares many of the same uptake mechanisms as norepinephrine in the rat heart. PET imaging studies with MBBG would be useful for assessing sympathetic nerve status in the living human heart

  2. Time-dependent changes of levels of endogenous epidermal growth factor in submandibular glands, in kidneys, and in urine in rats during systemic treatment with EGF

    DEFF Research Database (Denmark)

    Vinter-Jensen, Lars; Jørgensen, P E; Thulesen, J

    1998-01-01

    Exogenous EGF influences the levels of endogenous EGF differently in the submandibular glands (SMG) and the kidneys. The aim of the present study was to examine the time-dependent changes in levels of endogenous EGF during 1-4 weeks of EGF treatment.......Exogenous EGF influences the levels of endogenous EGF differently in the submandibular glands (SMG) and the kidneys. The aim of the present study was to examine the time-dependent changes in levels of endogenous EGF during 1-4 weeks of EGF treatment....

  3. Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor.

    Science.gov (United States)

    Dreyfus, Nicolas; Myers, Jason K; Badescu, Valentina O; de Frutos, Oscar; de la Puente, Maria Luz; Ding, Chunjin; Filla, Sandra A; Fynboe, Karsten; Gernert, Douglas L; Heinz, Beverly A; Hemrick-Luecke, Susan K; Johnson, Kirk W; Johnson, Michael P; López, Pilar; Love, Patrick L; Martin, Laura J; Masquelin, Thierry; McCoy, Michael J; Mendiola, Javier; Morrow, Denise; Muhlhauser, Mark; Pascual, Gustavo; Perun, Thomas J; Pfeifer, Lance A; Phebus, Lee A; Richards, Simon J; Rincón, Juan Antonio; Seest, Eric P; Shah, Jikesh; Shaojuan, Jia; Simmons, Rosa Maria A; Stephenson, Gregory A; Tromiczak, Eric G; Thompson, Linda K; Walter, Magnus W; Weber, Wayne W; Zarrinmayeh, Hamideh; Thomas, Craig E; Joshi, Elizabeth; Iyengar, Smriti; Johansson, Anette M

    2013-06-13

    The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug-drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions.

  4. Mechanisms of immune regulation by norepinephrine and cholera toxin

    International Nuclear Information System (INIS)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of β-adrenergic receptors. The role of β-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective β-adrenergic antagonists. The antagonists were metoprolol (β 1 -selective), ICI 118-551 (β 2 -selective), and propranolol (β-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, [ 3 H]CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% β 2 - and 25% β 1 -adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% β 2 -adrenergic receptors, while enriched B lymphocytes contained 90% β 2 -adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% β 2 -receptors, while 100% were β 2 receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous β-adrenergic receptor population on T lymphocytes and a more homogeneous β 2 -population on B lymphocytes

  5. Relationship between variations in the level of endogenous thiols and antioxidant activity of lipids and radiosensitivity of animals of different species

    International Nuclear Information System (INIS)

    Burlakova, E.B.; Graevskaya, B.M.; Ivanenko, G.F.; Shishkina, L.N.; AN SSSR, Moscow. Inst. Ehvolyutsionnoj Morfologii i Ehkologii Zhivotnykh)

    1978-01-01

    Initial levels of total and nonprotein sulfhydryl groups and antioxidant activity (AOA) of lipids of the spleen and liver are measured in animals of different species. Radiosensitivity of animals is assessed by the value of LDsub(50/30). No reliable correlation has been revealed between initial levels of endogenous thiols and AOA of lipids. There is a positive correlation between AOA of the spleen lipids and LDsub(50/30) as well as between the level of endogenous thiols and radioresistance of the animal species under study. It is likely that the level of endogenous thiols and AOA of lipids reflect various aspects of cellular metabolism which is responsible for radioresistance of the organism

  6. Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain.

    Science.gov (United States)

    Rastogi, R B; Singhal, R L

    1976-09-01

    In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats

  7. Radiosensitizing Effects of Ectopic miR-101 on Non–Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    International Nuclear Information System (INIS)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J.; Wang Ya

    2011-01-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non–small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription–polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein–lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  8. Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J. [Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA (United States); Wang Ya, E-mail: ywang94@emory.edu [Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2011-12-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  9. Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

    International Nuclear Information System (INIS)

    Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

    1987-01-01

    The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 μCi of [ 3 H]NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 μl/min over successive intervals of 5.0 min. When 0.05 or 0.1 μg/μl NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake

  10. Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia.

    Science.gov (United States)

    Strauss, Gregory P; Keller, William R; Koenig, James I; Sullivan, Sara K; Gold, James M; Buchanan, Robert W

    2015-03-01

    Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group×sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Mechanisms of immune regulation by norepinephrine and cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of {beta}-adrenergic receptors. The role of {beta}-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective {beta}-adrenergic antagonists. The antagonists were metoprolol ({beta}{sub 1}-selective), ICI 118-551 ({beta}{sub 2}-selective), and propranolol ({beta}-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, ({sup 3}H)CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% {beta}{sub 2}- and 25% {beta}{sub 1}-adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% {beta}{sub 2}-adrenergic receptors, while enriched B lymphocytes contained 90% {beta}{sub 2}-adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% {beta}{sub 2}-receptors, while 100% were {beta}{sub 2} receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous {beta}-adrenergic receptor population on T lymphocytes and a more homogeneous {beta}{sub 2}-population on B lymphocytes.

  12. Why we forget our dreams: Acetylcholine and norepinephrine in wakefulness and REM sleep.

    Science.gov (United States)

    Becchetti, Andrea; Amadeo, Alida

    2016-01-01

    The ascending fibers releasing norepinephrine and acetylcholine are highly active during wakefulness. In contrast, during rapid-eye-movement sleep, the neocortical tone is sustained mainly by acetylcholine. By comparing the different physiological features of the norepinephrine and acetylcholine systems in the light of the GANE (glutamate amplifies noradrenergic effects) model, we suggest how to interpret some functional differences between waking and rapid-eye-movement sleep.

  13. Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Antonio Paulo Nassar Junior

    Full Text Available BACKGROUND: Hepatorenal syndrome (HRS is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS. METHODS: We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events. RESULTS: Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23, mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17 and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45 between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83. CONCLUSIONS: Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

  14. The effects of elevated endogenous GABA levels on movement-related network oscillations.

    Science.gov (United States)

    Muthukumaraswamy, S D; Myers, J F M; Wilson, S J; Nutt, D J; Lingford-Hughes, A; Singh, K D; Hamandi, K

    2013-02-01

    The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    Science.gov (United States)

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  16. Myocardial imaging with a radioiodinated norepinephrine storage analog

    International Nuclear Information System (INIS)

    Wieland, D.M.; Brown, L.E.; Rogers, W.L.; Worthington, K.C.; Wu, J.L.; Clinthorne, N.H.; Otto, C.A.; Swanson, D.P.; Beierwaltes, W.H.

    1981-01-01

    Meta-iodobenzylguanidine (M-IBG), an iodinated aromatic analog of the hypotensive drug guanethidine, localizes in the heart of the rat, dog, and rhesus monkey. A comparative study of tissue distribution in the dog has been performed with five myocardiophilic agents: thallium-201, I-125 16-iodohexadecanoic acid, H-3 norepinephrine, C-14 guanethidine and I-125 M-IBG. The last two compounds give heart concentrations and heart-to-blood concentration ratios similar to those of thallium-201. Planar and tomographic images of the hearts of the dog and rhesus monkey were obtained using I-131 or I-123 labeled M-IBG. Blocking studies with reserpine suggest that a major component of myocardial retention of M-IBG is sequestration within the norepinephrine storage vesicles of the adrenergic nerves. The localization of M-IBG in other organs with rich sympathetic innervation and the relative insensitivity of myocardial uptake to a wide range of loading doses lend additional support for a neuronal mode of retention

  17. Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension.

    Science.gov (United States)

    Tourneux, Pierre; Rakza, Thameur; Bouissou, Antoine; Krim, Gérard; Storme, Laurent

    2008-09-01

    To evaluate the respiratory and the pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension (PPHN)-induced cardiac dysfunction. Inclusion criteria were: 1) Newborn infants >35 weeks gestational age; 2) PPHN treated with inhaled nitric oxide; and 3) symptoms of circulatory failure despite adequate fluid resuscitation. Lung function and pulmonary hemodynamic variables assessed with Doppler echocardiography were recorded prospectively before and after starting norepinephrine. Eighteen newborns were included (gestational age: 37 +/- 3 weeks; birth weight: 2800 +/- 700 g). After starting norepinephrine, systemic pressure and left ventricular output increased respectively from 33 +/- 4 mm Hg to 49 +/- 4 mm Hg and from 172 +/- 79 mL/kg/min to 209+/-90 mL/kg/min (P ventilatory variables have not been changed, the post-ductal transcutaneous arterial oxygen saturation increased from 89% +/- 1% to 95% +/- 4%, whereas the oxygen need decreased from 51% +/- 24% to 41% +/- 20% (P newborn infants with PPHN through a decrease in pulmonary/systemic artery pressure ratio and improved cardiac performance.

  18. Poly(norepinephrine)-coated open tubular column for the separation of proteins and recombination human erythropoietin by capillary electrochromatography.

    Science.gov (United States)

    Xiao, Xue; Zhang, Yamin; Wu, Jia; Jia, Li

    2017-12-01

    Recombinant human erythropoietin is an important therapeutic protein with high economic interest due to the benefits provided by its clinical use for the treatment of anemias associated with chronic renal failure and chemotherapy. In this work, a poly(norepinephrine)-coated open tubular column was successfully prepared based on the self-polymerization of norepinephrine under mild alkaline condition, the favorable film forming and easy adhesive properties of poly(norepinephrine). The poly(norepinephrine) coating was characterized by scanning electron microscopy and measurement of the electro-osmotic flow. The thickness of the coating was about 431 nm. The electrochromatographic performance of the poly(norepinephrine)-coated open tubular column was evaluated by separation of proteins. Some basic and acidic proteins including two variants of bovine serum albumin and two variants of β-lactoglobulin achieved separation in the poly(norepinephrine)-coated open tubular column. More importantly, the column demonstrated separation ability for the glycoforms of recombinant human erythropoietin. In addition, the column demonstrated good repeatability with the run-to-run, day-to-day, and column-to-column relative standard deviations of migration times of proteins less than 3.40%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

    2013-07-15

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

  20. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    International Nuclear Information System (INIS)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

    2013-01-01

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

  1. Variation in levels of non-starch polysaccharides and endogenous endo-1,4-β-xylanases affects the nutritive value of wheat for poultry.

    Science.gov (United States)

    Cardoso, V; Fernandes, E A; Santos, H M M; Maçãs, B; Lordelo, M M; Telo da Gama, Luis; Ferreira, L M A; Fontes, C M G A; Ribeiro, T

    2018-04-01

    1. Endo-1,4-β-xylanase is known to improve the nutritive value of wheat-based diets for poultry by degrading dietary arabinoxylans. However, broilers' response to supplementation of wheat-based diets with exogenous endo-1,4-β-xylanase is not always observed. 2. In this study, 108 different wheat lots were analysed for levels of extract viscosity as well as for endogenous endo-1,4-β-xylanase activity, and the impact of these two variables in animal performance was tested. 3. Results revealed that endogenous endo-1,4-β-xylanase activity and extract viscosity content varied widely among different wheat lots. Thus, a trial was conducted to evaluate the efficacy of exogenous enzyme supplementation in broiler diets using wheats with different levels of extract viscosity and endogenous endo-1,4-β-xylanase activity. 4. The data revealed that exogenous enzyme supplementation was only effective when the wheat present in the diet had high levels of extract viscosity (14.8 cP) with low endogenous endo-1,4-β-xylanase activity (347.0 U/kg). Nevertheless, it is apparent that exogenous microbial xylanases reduce digesta extract viscosity and feed conversion ratio independently of the endogenous properties presented by different wheat lots. 5. The data suggest that extract viscosity and/or endogenous endo-1,4-β-xylanase activity affect the response to enzyme supplementation by poultry fed on wheat-based diets.

  2. Arousal, exploration and the locus coeruleus-norepinephrine system

    NARCIS (Netherlands)

    Jepma, Marieke

    2011-01-01

    The studies described in this thesis address a range of topics related to arousal, exploration, temporal attention, and the locus coeruleus-norepinephrine (LC-NE) system. Chapters 2 and 3 report two studies that investigated a recent theory about the role of the LC-NE system in the regulation of the

  3. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    Science.gov (United States)

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  4. Endoluminal norepinephrine inhibits smooth muscle activity of the pig pyeloureter by stimulation of beta-adrenoceptors without side effects

    DEFF Research Database (Denmark)

    Mortensen, Jens; Holst, Uffe; Jacobsen, Jørn Skibsted

    2008-01-01

    of pyeloureter and to reveal possible side effects on cardiovascular and renal functions. Renal pelvis was perfused, while pelvic pressure, cardiovascular and renal functional parameters were recorded. In group A, a pelvic pressure increase was examined during pressure flow studies with norepinephrine solutions......It has been demonstrated in pigs that endoluminal administration of norepinephrine reduces the increase in renal pelvic pressure during perfusion. The purposes were to describe concentration-response relationship and receptor mechanism of the effect of norepinephrine on muscle function...... a renal pelvis pressure increase to perfusion in a dose-related way without side effects. Endoluminal norepinephrine is safe in pigs and may be useful under endoscopy of the pyeloureter....

  5. Endogenous zinc excretion in relation to various levels of dietary zinc intake in the mink (Mustela vison)

    International Nuclear Information System (INIS)

    Mejborn, H.

    1990-01-01

    Endogenous zinc excretion was studied in adult male mink fed experimental diets for 73 d, including a collection period from d 69 to 73. Dietary zinc levels were 2.8, 26 or 121 mg/kg wet weight. In accordance with the results of a methodological study, also reported here, the animals had an intramuscular injection of 65ZnCl2 12 d before the start of the collection period. Total fecal (endogenous + unabsorbed) zinc excretion for d 69-73 in the three groups was 2.3, 20.4 and 91.0 mg. The endogenous zinc excretion was 1.3, 2.0 and 6.4 mg, corresponding to 80.8, 10.6 and 6.4% of the zinc intake. Thus, the endogenous excretion was mainly important for the zinc homeostasis at low zinc intake, whereas at high intake the homeostasis was regulated via absorption from the digestive tract. The overall conclusion of the experiment was that mink are comparable to other species (including man) in regard to mechanisms controlling zinc homeostasis

  6. Radioenzymatic simultaneous determination of epinephrine and norepinephrine in plasma

    International Nuclear Information System (INIS)

    Mueller, T.

    1978-01-01

    The high-pressure liquid chromatography (= HPLC) was used in simultaneous determinations of a few pg epinephrine and norepinephrine. This separation procedure improves the efficiency when compared with the conventional thin-layer chromatographic methods (TLC) and allows routine assays in plasma. (orig.) [de

  7. Atomoxetine, a norepinephrine reuptake inhibitor, reduces seizure-induced respiratory arrest.

    Science.gov (United States)

    Zhang, Honghai; Zhao, Haiting; Feng, Hua-Jun

    2017-08-01

    Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA. It is well known that norepinephrine is an important neurotransmitter that modulates respiration and arousal in the brain as well. Therefore, we hypothesized that enhancing noradrenergic neurotransmission suppresses S-IRA. To test this hypothesis, we examined the effect of atomoxetine, a norepinephrine reuptake inhibitor (NRI), on S-IRA evoked by either acoustic stimulation or pentylenetetrazole in DBA/1 mice. We report the original observation that atomoxetine specifically suppresses S-IRA without altering the susceptibility to seizures evoked by acoustic stimulation, and atomoxetine also reduces S-IRA evoked by pentylenetetrazole in DBA/1 mice. Our data suggest that the noradrenergic signaling is importantly involved in S-IRA, and that atomoxetine, a medication widely used to treat attention deficit hyperactivity disorder (ADHD), is potentially useful to prevent SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Gold Nanoparticles-Based Barcode Analysis for Detection of Norepinephrine.

    Science.gov (United States)

    An, Jeung Hee; Lee, Kwon-Jai; Choi, Jeong-Woo

    2016-02-01

    Nanotechnology-based bio-barcode amplification analysis offers an innovative approach for detecting neurotransmitters. We evaluated the efficacy of this method for detecting norepinephrine in normal and oxidative-stress damaged dopaminergic cells. Our approach use a combination of DNA barcodes and bead-based immunoassays for detecting neurotransmitters with surface-enhanced Raman spectroscopy (SERS), and provides polymerase chain reaction (PCR)-like sensitivity. This method relies on magnetic Dynabeads containing antibodies and nanoparticles that are loaded both with DNA barcords and with antibodies that can sandwich the target protein captured by the Dynabead-bound antibodies. The aggregate sandwich structures are magnetically separated from the solution and treated to remove the conjugated barcode DNA. The DNA barcodes are then identified by SERS and PCR analysis. The concentration of norepinephrine in dopaminergic cells can be readily detected using the bio-barcode assay, which is a rapid, high-throughput screening tool for detecting neurotransmitters.

  9. Reward dependence is related to norepinephrine transporter T-182C gene polymorphism in a Korean population.

    Science.gov (United States)

    Ham, Byung-Joo; Choi, Myoung-Jin; Lee, Heon-Jeong; Kang, Rhee-Hun; Lee, Min-Soo

    2005-06-01

    It is well established that approximately 50% of the variance in personality traits is genetic. The goal of this study was to investigate a relationship between personality traits and the T-182C polymorphism in the norepinephrine transporter gene. The participants included 115 healthy adults with no history of psychiatric disorders and other physical illness during the past 6 months. All participants were tested with the Temperament and Character Inventory and genotyped norepinephrine transporter gene polymorphism. Differences on the Temperament and Character Inventory dimensions among three groups were examined with one-way analysis of variance. Our study suggests that the norepinephrine transporter T-182C gene polymorphism is associated with reward dependence in Koreans, but the small number of study participants and their sex and age heterogeneity limits generalization of our results. Further studies are necessary with a larger number of homogeneous participants to confirm whether the norepinephrine transporter gene is related to personality traits.

  10. Norepinephrine accumulation by the rat caudal artery in the presence of hypertensive plasma

    International Nuclear Information System (INIS)

    Freas, W.; Thompson, D.A.; Hart, J.L.; Muldoon, S.M.

    1986-01-01

    We have partially isolated endogenous factors from canine plasma which inhibit 3 H-norepinephrine (NE) accumulation by the canine saphenous vein. The purpose of this study is to determine if these circulating factors may account for the observed differences in 3 H-NE uptake by hypertensive and normotensive blood vessels. Three models of hypertension were examined in this study. Blood vessels were compared from SHR and WKY rats, deoxycorticosterone acetate (DOCA) and control rats, and reduced renal mass (RRM) and control rats. There was no significant difference in 3 H-NE accumulation between blood vessels obtained from RRM and paired control rats. However, both the SHR and DOCA hypertensive caudal arteries and aorta accumulated significantly more 3 H-NE than their corresponding control tissues. There was not a significant change in 3 H-NE accumulation between hypertensive and control vena cava and mesenteric arteries. Normotensive and hypertensive plasma inhibited 3 H-NE accumulation by the rat caudal artery. However, there was not a correlation between blood pressure of plasma donor rats and accumulation of 3 H-NE. Therefore, although there are differences in 3 H-NE accumulation between hypertensive and normotensive blood vessels, plasma does not contain a factor responsible for this observed difference

  11. Prejunctional inhibition of norepinephrine release caused by acetylcholine in the human saphenous vein

    International Nuclear Information System (INIS)

    Rorie, D.K.; Rusch, N.J.; Shepherd, J.T.; Vanhoutte, P.M.; Tyce, G.M.

    1981-01-01

    We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled with Krebs-Ringer solution. Acetylcholine depressed contractile responses to electric activation of the sympathetic nerve endings significantly more than those to exogenous norepinephrine; the relaxations caused by the cholinergic transmitter were antagonized by atropine. Helical strips were incubated with [/sub 3/H]norepinephrine and mounted for superfusion. Electric stimulation augmented the fractional release of labeled norepinephrine. Acetylcholine caused a depression of the evoked /sub 3/H release which was antagonized by atropine but not by hexamethonium. These experiments demonstrate that, as in animal cutaneous veins, there are prejunctional inhibitory muscarinic receptors on the adrenergic nerve endings in the human saphenous vein. By contrast, the human vein also contains postjunctional inhibitory muscarinic receptors

  12. Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line

    International Nuclear Information System (INIS)

    Tatsumi, M.; Takahashi, M.; Ohizumi, Y.

    1984-01-01

    Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin caused a release of [ 3 H]norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co 2+ or Ca 2+ -free medium, but was not modified by tetrodotoxin. The release of [ 3 H]norepinephrine induced by a low concentration of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased, but the release induced by a high concentration was unaffected by varying the concentration of external Na + . The release of [ 3 H]norepinephrine induced by both concentrations of palytoxin increased with increasing Ca 2+ concentrations. Palytoxin caused a concentration-dependent increase in 22 Na and 45 Ca influxes into pheochromocytoma cells. The palytoxin-induced 45 Ca influx was markedly inhibited by Co 2+ , whereas the palytoxin-induced 22 Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the [ 3 H]norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na + permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca 2+ influx into them

  13. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  14. Age-related differences in norepinephrine kinetics: Effect of posture and sodium-restricted diet

    International Nuclear Information System (INIS)

    Supiano, M.A.; Linares, O.A.; Smith, M.J.; Halter, J.B.

    1990-01-01

    We used compartmental analysis to study the influence of age on the kinetics of norepinephrine (NE) distribution and metabolism. Plasma NE and [3H]NE levels were measured in 10 young (age 19-33 yr) and 13 elderly (age 62-73 yr) subjects in the basal supine position, during upright posture, and after 1 wk of a sodium-restricted diet. We found that the basal supine release rate of NE into the extravascular compartment, which is the site of endogenous NE release (NE2), was significantly increased in the elderly group (young, 9.6 +/- 0.5; elderly, 12.3 +/- 0.8 nmol.min-1.m-2; means +/- SE; P = 0.016), providing direct evidence for an age-related increase in sympathetic nervous system (SNS) tone. Although upright posture led to a greater increase in plasma NE in the young (0.90 +/- 0.07 to 2.36 +/- 0.16 nM) than in the elderly (1.31 +/- 0.11 to 2.56 +/- 0.31 nM; age group-posture interaction, P = 0.02), the increase in NE2 was similar between the young (9.6 +/- 0.6 to 16.2 +/- 1.5 nmol.min-1.m-2) and the elderly (11.6 +/- 1.4 to 16.1 +/- 2.4 nmol.min-1.m-2; posture effect, P = 0.001; age group-posture interaction, P = 0.15). Thus the increase in SNS tone resulting from upright posture was similar in young and elderly subjects. Plasma NE levels increased similarly in both groups after a sodium-restricted diet (diet effect, P = 0.001; age group-diet interaction, P = 0.23). However, NE2 did not increase significantly in either group (diet effect, P = 0.26), suggesting that SNS tone did not increase after a sodium-restricted diet. Compartmental analysis provides a description of age-related differences in NE kinetics, including an age-related increase in the extravascular NE release rate

  15. Deployment of spatial attention to a structural framework: exogenous (alerting) and endogenous (goal-directed) factors.

    Science.gov (United States)

    Jefferies, Lisa N; Di Lollo, Vincent

    2017-10-01

    The main question examined in the present work was whether spatial attention can be deployed to an appropriate structural framework not only endogenously when the framework is displayed continuously, as in previous work, but also exogenously, when it is displayed transiently 100 ms before the target. The results of five experiments answered that question in the negative. We found that the onset transient triggered by a brief presentation of the structural framework did enhance the response to the upcoming target. That enhancement, however, was due not to the framework itself but to the alerting effect produced by its sudden onset, witness the finding that the same enhancement was produced by an onset transient triggered by a featureless stimulus (i.e., by a brief dimming of the entire screen, in the absence of a structural framework). We conclude that spatial attention can be deployed to the region demarcated by a structural framework when it is deployed endogenously but not when it is deployed exogenously. A theoretical account of the results is proposed in terms of the temporal dynamics of the locus cœruleus/norepinephrine neuromodulatory system.

  16. Development of norepinephrine transporter reuptake inhibition assays using SK-N-BE(2C cells

    Directory of Open Access Journals (Sweden)

    Ann M. Decker

    2018-05-01

    Full Text Available This report describes efforts to develop and validate novel norepinephrine transporter reuptake inhibition assays using human neuroblastoma SK-N-BE(2C cells in 24-well format. Before conducting the assays, the SK-N-BE(2C cells were first evaluated for their ability to uptake [3H]norepinephrine and were shown to have a saturable uptake with a KM value of 416 nM. Using this determined KM value, reuptake inhibition assays were then conducted with a variety of ligands including antidepressants, as well as piperazine and phenyltropane derivatives. The results obtained with the SK-N-BE(2C cells indicate that this model system can detect a range of ligand potencies, which compare well with other established transporter assays. Our data suggest that SK-N-BE(2C cells have potential utility to serve as another model system to detect norepinephrine reuptake inhibition activity.

  17. Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors.

    Science.gov (United States)

    Yamaguchi, T; Suzuki, M; Yamamoto, M

    1997-12-01

    Effects of indeloxazine hydrochloride, an inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake with a facilitatory effect on 5-HT release, on acetylcholine (ACh) output in frontal cortex of conscious rats were characterized using an in vivo microdialysis technique. Systemic administration of indeloxazine (3 and 10 mg/kg, i.p.) increased ACh and 5-HT output in a dose-dependent manner. Depletion of endogenous monoamines by reserpine and of 5-HT by p-chlorophenylalanine, but not that of catecholamines by alpha-methyl-p-tyrosine, significantly attenuated the facilitatory effect of indeloxazine on ACh release. When applied locally by reverse dialysis, indeloxazine (10 and 30 microM) and the selective 5-HT reuptake inhibitor citalopram (10 microM), but not the NE reuptake inhibitor maprotiline (30 microM), increased cortical ACh output. Indeloxazine (10 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (100 microM), 5-HT1A/1B/beta-adrenoceptor antagonist (-)propranolol (150 microM), 5-HT2A/2C antagonist ritanserin (10 microM) and 5-HT3 antagonist ondansetron (10 microM) failed to significantly modify this effect. Neither depletion of monoamines nor treatment with serotonergic antagonists significantly changed the basal ACh level, indicating that endogenous monoamines do not tonically activate ACh release. These results suggest that indeloxazine-induced facilitation of ACh release in rat frontal cortex is mediated by endogenous 5-HT and involves at least in part cortical 5-HT4 receptors.

  18. Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly

    DEFF Research Database (Denmark)

    Madsen, Michael; Fisker, Sanne; Feldt-Rasmussen, Ulla

    2014-01-01

    OBJECTIVE: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. PATIENTS AND METHODS: Seventeen patients (6 women), mean age 46·3 years (range: 23...... correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. CONCLUSIONS: (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum...

  19. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  20. Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

    Science.gov (United States)

    Muthukumaraswamy, Suresh D; Myers, Jim F M; Wilson, Sue J; Nutt, David J; Hamandi, Khalid; Lingford-Hughes, Anne; Singh, Krish D

    2013-01-01

    The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. PMID:23361120

  1. Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

    Science.gov (United States)

    Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

    2017-03-01

    Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Stimulatory effects of neuronally released norepinephrine on renin release in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))

    1988-10-01

    Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

  3. Fluid loading and norepinephrine infusion mask the left ventricular preload decrease induced by pleural effusion

    DEFF Research Database (Denmark)

    Wemmelund, Kristian Borup; Ringgård, Viktor Kromann; Vistisen, Simon Tilma

    2017-01-01

    BACKGROUND: Pleural effusion (PLE) may lead to low blood pressure and reduced cardiac output. Low blood pressure and reduced cardiac output are often treated with fluid loading and vasopressors. This study aimed to determine the impact of fluid loading and norepinephrine infusion on physiologic d...... global haemodynamic parameters. Inferior vena cava distensibility remained unchanged. The haemodynamic significance of PLE may be underestimated during fluid or norepinephrine administration, potentially masking the presence of PLE....

  4. Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.

    Science.gov (United States)

    Daniele, Thiago Medeiros da Costa; de Bruin, Pedro Felipe Carvalhedo; Rios, Emiliano Ricardo Vasconcelos; de Bruin, Veralice Meireles Sales

    2017-08-14

    Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Time dependent changes in myocardial norepinephrine concentration and adrenergic receptor density following X-irradiation of the rat heart

    NARCIS (Netherlands)

    Franken, N. A.; van der Laarse, A.; Bosker, F. J.; Reynart, I. W.; van Ravels, F. J.; Strootman, E.; Wondergem, J.

    1992-01-01

    The hearts of 9 to 12-weeks-old Sprague-Dawley rats were locally irradiated with a single dose of 20 Gy. The effects on myocardial norepinephrine concentrations and on alpha-adrenergic and beta-adrenergic receptor densities was examined up to 16 months post-treatment. Myocardial norepinephrine

  6. Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women

    Directory of Open Access Journals (Sweden)

    Iwasaki Motoki

    2012-07-01

    Full Text Available Abstract Background Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA. Methods A cross-sectional study was conducted using the control group of a breast cancer case–control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses. Results Mean global methylation level (standard deviation was 70.3% (3.1 and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estrone while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA. Conclusions Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.

  7. The conversion of dopamine to epinephrine and nor-epinephrine is ...

    African Journals Online (AJOL)

    Tyrosine is a conditionally non-essential large neutral amino acid and the precursor of the neurotransmitters dopamine, nor-epinephrine and epinephrine. Ante-mortem stress experienced by an animal may be influenced by amino acids that provide substrates for neurotransmitter synthesis. The Nguni type cattle showed ...

  8. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses.

    Science.gov (United States)

    Arjan-Odedra, Shetal; Swanson, Chad M; Sherer, Nathan M; Wolinsky, Steven M; Malim, Michael H

    2012-06-22

    The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.

  9. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    International Nuclear Information System (INIS)

    Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

    2012-01-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  10. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    Energy Technology Data Exchange (ETDEWEB)

    Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

    2012-11-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  11. Cognitive function and endogenous cytokine levels in children with chronic hepatitis C.

    Science.gov (United States)

    Abu Faddan, N H; Shehata, G A; Abd Elhafeez, H A; Mohamed, A O; Hassan, H S; Abd El Sameea, F

    2015-08-01

    Little is known about how hepatitis C (HCV) infection affects cognitive function in children. The aim of the study was to assess the impact of HCV infection on cognitive function of children with normal liver functions and their relationships to endogenous IFN-α, IL-6 and TNF-α. IFN-α, IL-6 and TNF-α were measured and the Arabic version of the Stanford-Binet test used to assess cognitive functions in 35 children with HCV infection and 23 controls. Serum levels of IL-6 and IFN-α were significantly higher in patients compared to controls. There was a significant effect on vocabulary, comprehension, and abstract visual reasoning, quantitative reasoning and bead memory tests, as well as total short-term memory and intelligence quotient in patients compared to controls. There was a significant positive correlation between IFN-α and IL-6. Also there were significant negative correlations between IFN-α and Abstract visual reasoning test, Quantitative reasoning test, Bead memory test, Total short-term memory and Intelligence quotient; and between IL-6 and Abstract visual reasoning test, Quantitative reasoning test and Intelligence quotient. There was no significant correlation between TNF-α and any of the cognitive functions. Cytokine levels were not related to demographic characteristics of the patients or viral load (PCR). Children with chronic hepatitis C infection in its early stages showed signs of cognitive impairment, with the memory tasks being mostly affected. There was a significant correlation between endogenous cytokines and cognitive impairment in these children. Further studies are needed to define the effect of successful antiviral treatment. © 2014 John Wiley & Sons Ltd.

  12. A comparison of N-methyl-D-aspartate-evoked release of adenosine and [3H]norepinephrine from rat cortical slices

    International Nuclear Information System (INIS)

    Hoehn, K.; Craig, C.G.; White, T.D.

    1990-01-01

    Tetrodotoxin reduced N-methyl-D-aspartate (NMDA)-evoked release of adenosine by 35% but virtually abolished [3H]norepinephrine release. Although [3H]norepinephrine release from rat cortical slices evoked by 500 microM NMDA was abolished by 1.2 mM Mg++, which produces a voltage-sensitive, uncompetitive block of NMDA-channels, adenosine release was increased in the presence of Mg++. Partial depolarization with 12 mM K+ relieved the Mg++ block of 500 microM NMDA-evoked [3H]norepinephrine release but did not affect adenosine release, indicating that a Mg++ requirement for the adenosine release process per se cannot account for this discrepancy. NMDA was 33 times more potent in releasing adenosine than [3H]norepinephrine. At submaximal concentrations of NMDA (10 and 20 microM), adenosine release was augmented in Mg+(+)-free medium. Although a high concentration of the uncompetitive NMDA antagonist MK-801 [(+)-5-methyl-10,11,dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine maleate] (3 microM) blocked NMDA-evoked release of [3H]norepinephrine and adenosine, a lower concentration (300 nM) decreased NMDA-evoked [3H]norepinephrine release by 66% without affecting adenosine release. These findings suggest that maximal adenosine release occurs when relatively few NMDA receptors are activated, raising the possibility that spare receptors exist for NMDA-evoked adenosine release. Rather than acting as a protectant against excessive NMDA excitation, released adenosine might provide an inhibitory threshold which must be overcome for NMDA-mediated neurotransmission to proceed

  13. Whole body clearance of norepinephrine. The significance of arterial sampling and of surgical stress

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Madsbad, S

    1983-01-01

    The whole body clearance of norepinephrine (NE) was measured in seven patients pre- and postoperatively. L[(3)H]NE was infused intravenously for 90 min and steady-state concentrations of L[(3)H]NE were measured at 75 and 90 min in both arterial and peripheral venous blood. Preoperatively, in the ......The whole body clearance of norepinephrine (NE) was measured in seven patients pre- and postoperatively. L[(3)H]NE was infused intravenously for 90 min and steady-state concentrations of L[(3)H]NE were measured at 75 and 90 min in both arterial and peripheral venous blood. Preoperatively...

  14. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: tsucchy@fmsrsa.fukui-med.ac.jp; Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Yoshida, Yoshio [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Itoh, Harumi [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)

    2007-02-15

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16{alpha}-[{sup 18}F]fluoro-17{beta}-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03{+-}1.05 vs. 3.97{+-}1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration.

  15. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    International Nuclear Information System (INIS)

    Tsuchida, Tatsuro; Okazawa, Hidehiko; Mori, Tetsuya; Kobayashi, Masato; Yoshida, Yoshio; Fujibayashi, Yasuhisa; Itoh, Harumi

    2007-01-01

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16α-[ 18 F]fluoro-17β-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03±1.05 vs. 3.97±1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration

  16. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

    Science.gov (United States)

    2012-01-01

    Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. PMID:22727223

  17. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  18. Fluid loading and norepinephrine infusion mask the left ventricular preload decrease induced by pleural effusion.

    Science.gov (United States)

    Wemmelund, Kristian Borup; Ringgård, Viktor Kromann; Vistisen, Simon Tilma; Hyldebrandt, Janus Adler; Sloth, Erik; Juhl-Olsen, Peter

    2017-09-11

    Pleural effusion (PLE) may lead to low blood pressure and reduced cardiac output. Low blood pressure and reduced cardiac output are often treated with fluid loading and vasopressors. This study aimed to determine the impact of fluid loading and norepinephrine infusion on physiologic determinants of cardiac function obtained by ultrasonography during PLE. In this randomised, blinded, controlled laboratory study, 30 piglets (21.9 ± 1.3 kg) had bilateral PLE (75 mL/kg) induced. Subsequently, the piglets were randomised to intervention as follows: fluid loading (80 mL/kg/h for 1.5 h, n = 12), norepinephrine infusion (0.01, 0.03, 0.05, 0.1, 0.2 and 0.3 μg/kg/min (15 min each, n = 12)) or control (n = 6). Main outcome was left ventricular preload measured as left ventricular end-diastolic area. Secondary endpoints included contractility and afterload as well as global measures of circulation. All endpoints were assessed with echocardiography and invasive pressure-flow measurements. PLE decreased left ventricular end-diastolic area, mean arterial pressure and cardiac output (p values  0.05) to baseline. Left ventricular contractility increased with norepinephrine infusion (p = 0.002), but was not affected by fluid loading (p = 0.903). Afterload increased in both active groups (p values > 0.001). Overall, inferior vena cava distensibility remained unchanged during intervention (p values ≥ 0.085). Evacuation of PLE caused numerical increases in left ventricular end-diastolic area, but only significantly so in controls (p = 0.006). PLE significantly reduced left ventricular preload. Both fluid and norepinephrine treatment reverted this effect and normalised global haemodynamic parameters. Inferior vena cava distensibility remained unchanged. The haemodynamic significance of PLE may be underestimated during fluid or norepinephrine administration, potentially masking the presence of PLE.

  19. The issue of HPLC determination of endogenous lipoic acid in human plasma.

    Science.gov (United States)

    Sechovcová, Soňa; Královcová, Pavla; Kanďár, Roman; Ventura, Karel

    2018-05-01

    Lipoic acid (LA) is used extensively as a therapeutic agent for the treatment of various diseases. Many methods have been reported for the determination of LA plasma levels and its metabolites after its supplementation, but available information concerning endogenous plasma levels is still scarce. Studies which directly focused on determining the endogenous plasma levels provided highly controversial results, endogenous plasma levels of LA: 2.4 and 4.9 nmol/L respectively. However, the levels of free LA in the plasma of nonsupplemented voluntary blood donors were not detectable in all cases. The presented results of our study show that endogenous concentrations of LA are <1.85 nmol/L. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Increased release of norepinephrine and dopamine from canine kidney during bilateral carotid occlusion

    International Nuclear Information System (INIS)

    Bradley, T.; Hjemdahl, P.; DiBona, G.F.

    1987-01-01

    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 renal venous catecholamine outflow, they corrected for the renal extraction of arterial catecholamines, assessed as the extractions of [ 3 H]NE, [ 3 H]DA, or endogenous Epi. The [ 3 H]NE corrected renal NE overflow to plasma increased from 144 +/- 40 to 243 +/- 64 pmol-min -1 during BCO, which, when compared with a previous study of the [ 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 ∼ 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

  1. The norepinephrine transporter gene is a candidate gene for panic disorder

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Kristensen, A S; Buch, H N

    2011-01-01

    Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis...

  2. Influence of norepinephrine transporter inhibition on hemodynamic response to hypergravitation

    OpenAIRE

    Strempel, Sebastian

    2011-01-01

    Background: Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. Methods. We performed a double-blind, randomized...

  3. Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

    Science.gov (United States)

    Navarro-Meléndez, Ariana L; Heil, Martin

    2014-07-01

    Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

  4. Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.

    Science.gov (United States)

    Yamawaki, Kousuke; Zamami, Yoshito; Kawasaki, Hiromu; Takatori, Shingo

    2017-05-05

    Vascular adrenergic nerves mainly regulate the tone of blood vessels. Calcitonin gene-related peptide-containing (CGRPergic) vasodilator nerves also participate in the regulation of vascular tone. Furthermore, there are nitric oxide (NO)-containing (nitrergic) nerves, which include NO in blood vessels as vasodilator nerves, but it remains unclear whether nitrergic nerves participate in vascular regulation. The present study investigated the role of nitrergic nerves in vascular responses to spinal cord stimulation (SCS) and vasoactive agents in pithed rats. Wistar rats were anesthetized and pithed, and vasopressor responses to SCS and injections of norepinephrine were observed. To evaluate vasorelaxant responses, the BP was increased by a continuous infusion of methoxamine with hexamethonium to block autonomic outflow. After the elevated BP stabilized, SCS and injections of acetylcholine (ACh), sodium nitroprusside (SNP), and CGRP were intravenously administered. We then evaluated the effects of the NO synthase (NOS) inhibitor, N-ω-nitro-L-arginine methylester hydrochloride (L-NAME), on these vascular responses. Pressor responses to SCS and norepinephrine in pithed rats were enhanced by L-NAME, while the combined infusion of L-NAME and L-arginine had no effect on these responses. L-NAME infusion significantly increased the release of norepinephrine evoked by SCS. In pithed rats with artificially increased BP and L-NAME infusion, depressor response to ACh (except for 0.05nmol/kg) was suppressed and SNP (only 2nmol/kg) was enhanced. However, depressor responses to SCS and CGRP were similar to control responses. The present results suggest endogenous NO regulates vascular tone through endothelium function and inhibition of adrenergic neurotransmission, but not through CGRPergic nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

    International Nuclear Information System (INIS)

    Yang, R.; Lin, Q.; Gao, H.B.; Zhang, P.

    2014-01-01

    In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression

  6. Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.; Lin, Q.; Gao, H.B.; Zhang, P. [Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai (China)

    2014-02-17

    In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.

  7. P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism.

    Science.gov (United States)

    Gen, R; Akbay, E; Camsari, A; Ozcan, T

    2010-02-01

    The aim of this study was to measure maximum P wave duration (Pmax) and P wave dispersion (PWD), which can be indicators for the risk of paroxysmal atrial fibrillation when increased, and to reveal their relationship with thyroid hormone levels in patients with endogenous and exogenous subclinical hyperthyroidism. Seventy-one patients with sublinical thyrotoxicosis (34 endogenous, 37 exogenous) and 69 healthy individuals were enrolled in the study. Pmax and minimum P wave duration (Pmin) on electrocardiogram recordings were measured and PWD was calculated as Pmax-Pmin. Pmax (pendogenous subclinical hyperthyroidism compared with the control group. Pmax (pexogenous subclinical thyrotoxicosis compared with the control group. Pmax (p=0.710) and PWD (p=0.127) were not significantly different in patients with endogenous subclinical hyperthyroidism compared with exogenous subclinical hyperthyroid patients. Pmax and PWD negatively associated with TSH in endogenous and exogenous subclinical hyperthyroidism. In the present study, we observed that Pmax and PWD were longer in patients with endogenous and exogenous subclinical hyperthyroidism. Lack of a difference in Pmax and PWD between patients with endogenous and exogenous subclinical hyperthyroidism seems to support the idea that hormone levels rather than the etiology of thyrotoxicosis affect the heart.

  8. High-Level Accumulation of Exogenous Small RNAs Not Affecting Endogenous Small RNA Biogenesis and Function in Plants

    Institute of Scientific and Technical Information of China (English)

    SHEN Wan-xia; Neil A Smith; ZHOU Chang-yong; WANG Ming-bo

    2014-01-01

    RNA silencing is a fundamental plant defence and gene control mechanism in plants that are directed by 20-24 nucleotide (nt) small interfering RNA (siRNA) and microRNA (miRNA). Infection of plants with viral pathogens or transformation of plants with RNA interference (RNAi) constructs is usually associated with high levels of exogenous siRNAs, but it is unclear if these siRNAs interfere with endogenous small RNA pathways and hence affect plant development. Here we provide evidence that viral satellite RNA (satRNA) infection does not affect siRNA and miRNA biogenesis or plant growth despite the extremely high level of satRNA-derived siRNAs. We generated transgenic Nicotiana benthamiana plants that no longer develop the speciifc yellowing symptoms generally associated with infection by Cucumber mosaic virus (CMV) Y-satellite RNA (Y-Sat). We then used these plants to show that CMV Y-Sat infection did not cause any visible phenotypic changes in comparison to uninfected plants, despite the presence of high-level Y-Sat siRNAs. Furthermore, we showed that the accumulation of hairpin RNA (hpRNA)-derived siRNAs or miRNAs, and the level of siRNA-directed transgene silencing, are not signiifcantly affected by CMV Y-Sat infection. Taken together, our results suggest that the high levels of exogenous siRNAs associated with viral infection or RNAi-inducing transgenes do not saturate the endogenous RNA silencing machineries and have no signiifcant impact on normal plant development.

  9. Levels of endogenous regulatory factors in liquidators of consequences of the Chernobyl accident

    International Nuclear Information System (INIS)

    Liasko, L.I.; Souchkevitch, G.N.; Tsyb, A.F.

    1997-01-01

    Dynamics of endogenous regulatory factor levels was studied in liquidators of consequences of the Chernobyl accident (mean age - 42 years). Irradiation dose for 90% of examined individuals was within 100 mSv range. We observed a decreased level of synthesis of intracellular processes regulators (cAMP, cGMP) and biased ratio of arachidonic acid metabolites (TxB2, 6-Keto-PGF1α) in persons worked in the zone of accident at different time during the period of 1986-1988. The parameters measured were preserved even 4 years later and the changes apparently did not depend on the individual's age and work conditions. However they were most pronounced in liquidators of 1986 and in those who stayed in the Chernobyl accident zone for a long time. There was no evident connection between the dose and extent of the parameter alterations. (author)

  10. Are endogenous feline leukemia viruses really endogenous?

    Science.gov (United States)

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Contagion risk in endogenous financial networks

    International Nuclear Information System (INIS)

    Li, Shouwei; Sui, Xin

    2016-01-01

    Highlights: • We propose an endogenous financial network model. • Endogenous networks include interbank networks, inter-firm networks and bank-firm networks. • We investigate contagion risk in endogenous financial networks. - Abstract: In this paper, we investigate contagion risk in an endogenous financial network, which is characterized by credit relationships connecting downstream and upstream firms, interbank credit relationships and credit relationships connecting firms and banks. The findings suggest that: increasing the number of potential lenders randomly selected can lead to an increase in the number of bank bankruptcies, while the number of firm bankruptcies presents a trend of increase after the decrease; after the intensity of choice parameter rises beyond a threshold, the number of bankruptcies in three sectors (downstream firms, upstream firms and banks) shows a relatively large margin of increase, and keeps at a relatively high level; there exists different trends for bankruptcies in different sectors with the change of the parameter of credits’ interest rates.

  12. Endogenous antipyretics.

    Science.gov (United States)

    Roth, Joachim

    2006-09-01

    The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

  13. Spatiotemporal norepinephrine mapping using a high-density CMOS microelectrode array.

    Science.gov (United States)

    Wydallis, John B; Feeny, Rachel M; Wilson, William; Kern, Tucker; Chen, Tom; Tobet, Stuart; Reynolds, Melissa M; Henry, Charles S

    2015-10-21

    A high-density amperometric electrode array containing 8192 individually addressable platinum working electrodes with an integrated potentiostat fabricated using Complementary Metal Oxide Semiconductor (CMOS) processes is reported. The array was designed to enable electrochemical imaging of chemical gradients with high spatiotemporal resolution. Electrodes are arranged over a 2 mm × 2 mm surface area into 64 subarrays consisting of 128 individual Pt working electrodes as well as Pt pseudo-reference and auxiliary electrodes. Amperometric measurements of norepinephrine in tissue culture media were used to demonstrate the ability of the array to measure concentration gradients in complex media. Poly(dimethylsiloxane) microfluidics were incorporated to control the chemical concentrations in time and space, and the electrochemical response at each electrode was monitored to generate electrochemical heat maps, demonstrating the array's imaging capabilities. A temporal resolution of 10 ms can be achieved by simultaneously monitoring a single subarray of 128 electrodes. The entire 2 mm × 2 mm area can be electrochemically imaged in 64 seconds by cycling through all subarrays at a rate of 1 Hz per subarray. Monitoring diffusional transport of norepinephrine is used to demonstrate the spatiotemporal resolution capabilities of the system.

  14. Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells.

    Science.gov (United States)

    Barazzuol, Lara; Rickett, Nicole; Ju, Limei; Jeggo, Penny A

    2015-10-01

    The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We demonstrate that, although DSBs do not arise at a high frequency in adult neural stem cells, the low numbers of DSBs that persist endogenously in Lig4(Y288C) mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice. © 2015. Published by The Company of Biologists Ltd.

  15. α2-Adrenergic regulation of galanin and norepinephrine release from canine pancreas

    NARCIS (Netherlands)

    Scheurink, Anton J.W.; Mundinger, Thomas O.; Dunning, Beth E.; Veith, Richard C.; Taborsky, Jr.

    1992-01-01

    We found previously that electrical stimulation of the mixed autonomic pancreatic nerves (MPNS) in anesthesized dogs elicits marked and rapid increases of pancreatic output of both norepinephrine (NE) and galanin, and on that basis hypothesized a role for galanin as a sympathetic cotransmitter in

  16. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    International Nuclear Information System (INIS)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of [ 3 H] norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 x 10 -5 -10 -3 M, enhanced potassium stimulated [ 3 H] norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of [ 3 H] norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA A receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA A agonist muscimol, 10 -4 M, mimicked the effect of GABA, but the GABA B agonist (±)baclofen, 10 -4 M, did not affect the release of [ 3 H] norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA A , but not GABA B , receptors. In contrast to the results that would be predicted for an event involving GABA A receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10 -8 and 10 -4 M. Thus these receptors may constitute a subclass of GABA A receptors. These results support a role of GABA uptake and GABA A receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat

  17. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  18. Epinephrine in the heart: uptake and release, but no facilitation of norepinephrine release

    NARCIS (Netherlands)

    Th.W. Lameris (Thomas); P.A. de Zeeuw (Sandra); D.J.G.M. Duncker (Dirk); W. Tietge; G. Alberts; F. Boomsma (Frans); P.D. Verdouw (Pieter); A.H. van den Meiracker (Anton)

    2002-01-01

    textabstractBACKGROUND: Several studies have suggested that epinephrine augments the release of norepinephrine from sympathetic nerve terminals through stimulation of presynaptic receptors, but evidence pertaining to this mechanism in the heart is scarce and conflicting. Using

  19. Combining Semi-Endogenous and Fully Endogenous Growth: a Generalization.

    OpenAIRE

    Cozzi, Guido

    2017-01-01

    This paper shows that combining the semi-endogenous and the fully endogenous growth mechanisms with a general CES aggregator, either growth process can prevail in the balanced growth path depending on their degree of complementarity/substitutability. Policy-induced long-run economic switches to the fully endogenous steady state as the R&D employment ratio surpasses a positive threshold are possible if the two growth engines are gross substitutes.

  20. Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA

    Science.gov (United States)

    Cases, Olivier; Grimsby, Joseph; Gaspar, Patricia; Chen, Kevin; Pournin, Sandrine; Müller, Ulrike; Aguet, Michel; Babinet, Charles; Shih, Jean Chen; De Maeyer, Edward

    2010-01-01

    Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males. PMID:7792602

  1. Activation of beta2-Adrenoceptor Enhances Synaptic Potentiation and Behavioral Memory via cAMP-PKA Signaling in the Medial Prefrontal Cortex of Rats

    Science.gov (United States)

    Zhou, Hou-Cheng; Sun, Yan-Yan; Cai, Wei; He, Xiao-Ting; Yi, Feng; Li, Bao-Ming; Zhang, Xue-Han

    2013-01-01

    The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation, behavioral inhibition, as well as memory storage. The functions of PFC are very sensitive to norepinephrine (NE), and even low levels of endogenously released NE exert a dramatic influence on the functioning of the PFC.…

  2. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  3. Determining level of endogenous serum erythropoietin for differential diagnosis of polycythemia vera and symptomatic polycythemia

    Directory of Open Access Journals (Sweden)

    Kostyukevych O.M.

    2013-06-01

    Full Text Available The article deals with determining possibility of the assessment of the level of endogenous serum erythropoietin (EPO for differential diagnosis of polycythemia vera (PV and secondary erythrocytosis (SE. The determination of subnormal level of this cytokine for the diagnosis of PV has been detected. The relation between the level of endogenous erythropoietin and iron metabolism also has been analyzed. The study involved 88 patients with PV and 119 patients with SE. Statistically significant decrease in EPO concentration level has been detected in PV patients. The mean EPO level was equal to 6.38 ± 0.84 mIU/mL and 17.98 ±2.48 mIU/mL in PV and SE patients respectively. In control group of individuals EPO concentration was equal to 9,81 ±0,58 mIU/mL, the significant difference was found between all studied groups (р<0.01. According to our data, EPO was increased in 28 SE patients (23.53%, it was not observed in control group and in group of PV patients (φ*emp = 4.355, р<0.01. The decrease of EPO level in PV patients has been detected more often than in SE patients (84.09% versus 11.76% , φ*emp = 5.218, р<0.01, it has not been observed in control group. Only 14 (15.91% PV patients had normal EPO level, in contrast 77 (64.71% SE patients demonstrated normal EPO level (φ*emp = 4.578, р<0.01. The average level of ferritin was equal to 57.41 ± 9.74 ng/mL in PV patients and 199.77 ± 14.32 ng/mL in SE patients (р<0.01. Significantly more patients with PV demonstrated decrease of ferritin level (31.81% versus 7.56%, φ*emp = 4.438, р<0.01. Patients with SE more often had raised level of EPO than PV patients (15.12% versus 4.54%, φ*emp = 2.453, р<0.01. The sensitivity of test with detecting of the reduced level of EPO for the diagnosis of PV was 84.1%, specificity - 87.4%, positive predictive value - 83.1%, negative predictive value - 88.1%. Normal range of EPO significantly (rs = 0,5494 correlated with decreased levels of serum ferritin in

  4. Norepinephrine and dopamine increase motility, biofilm formation and virulence of Vibrio harveyi

    Directory of Open Access Journals (Sweden)

    Qian eYang

    2014-11-01

    Full Text Available Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine and dopamine increased growth in serum-supplemented medium, siderophore production, swimming motility and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, norepinephrine-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopamine-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesise that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host.

  5. High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis

    NARCIS (Netherlands)

    Lin, Cong; von der Thüsen, Jan; Isermann, Berend; Weiler, Hartmut; van der Poll, Tom; Borensztajn, Keren; Spek, Chris A.

    2016-01-01

    Coagulation activation accompanied by reduced anticoagulant activity is a key characteristic of patients with idiopathic pulmonary fibrosis (IPF). Although the importance of coagulation activation in IPF is well studied, the potential relevance of endogenous anticoagulant activity in IPF progression

  6. Chronic desipramine treatment alters tyrosine hydroxylase but not norepinephrine transporter immunoreactivity in norepinephrine axons in the rat prefrontal cortex

    Science.gov (United States)

    Erickson, Susan L.; Gandhi, Anjalika R.; Asafu-Adjei, Josephine K.; Sampson, Allan R.; Miner, LeeAnn; Blakely, Randy D.; Sesack, Susan R.

    2011-01-01

    Pharmacological blockade of norepinephrine (NE) reuptake is clinically effective in treating several mental disorders. Drugs that bind to the NE transporter (NET) alter both protein levels and activity of NET and also the catecholamine synthetic enzyme tyrosine hydroxylase (TH). We examined the rat prefrontal cortex (PFC) by electron microscopy to determine whether the density and subcellular distribution of immunolabeling for NET and colocalization of NET with TH within individual NE axons were altered by chronic treatment with the selective NE uptake inhibitor desipramine (DMI). Following DMI treatment (21 days, 15 mg/kg/day), NET-immunoreactive (-ir) axons were significantly less likely to colocalize TH. This finding is consistent with reports of reduced TH levels and activity in the locus coeruleus after chronic DMI and indicates a reduction of NE synthetic capacity in the PFC. Measures of NET expression and membrane localization, including the number of NET-ir profiles per tissue area sampled, the number of gold particles per NET-ir profile area, and the proportion of gold particles associated with the plasma membrane, were similar in DMI and vehicle treated rats. These findings were verified using two different antibodies directed against distinct epitopes of the NET protein. The results suggest that chronic DMI treatment does not reduce NET expression within individual NE axons in vivo or induce an overall translocation of NET protein away from the plasma membrane in the PFC as measured by ultrastructural immunogold labeling. Our findings encourage consideration of possible postranslational mechanisms for regulating NET activity in antidepressant-induced modulation of NE clearance. PMID:21208501

  7. Invasive fungal infections in endogenous Cushing's syndrome

    Science.gov (United States)

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  8. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  9. Effects of surgical stress and insulin on cardiovascular function and norepinephrine kinetics

    DEFF Research Database (Denmark)

    Christensen, N J; Hilsted, J; Hegedüs, Laszlo

    1984-01-01

    In resting supine subjects the whole-body clearance of norepinephrine (NE) based on arterial and venous sampling averaged 1.4 and 2.5 liters/min, respectively (P less than 0.02). The difference in clearance values was due to a peripheral uptake of NE averaging 45%. The calculation of plasma NE...

  10. External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine

    International Nuclear Information System (INIS)

    Shah, S.D.; Clutter, W.E.; Cryer, P.E.

    1985-01-01

    In plasma from normal humans (n = 9, 35 samples) and from patients with diabetes mellitus (n = 12, 24 samples) single-isotope derivative (radioenzymatic) plasma norepinephrine and epinephrine concentrations calculated from external standard curves constructed in a normal plasma pool were identical to those calculated from internal standards added to an aliquot of each plasma sample. In plasma from patients with end-stage renal failure receiving long-term dialysis (n = 34, 109 samples), competitive catechol-O-methyltransferase (COMT) inhibitory activity resulted in a systematic error when external standards in a normal plasma pool were used, as reported previously; values so calculated averaged 21% (+/- 12%, SD) lower than those calculated from internal standards. However, when external standard curves were constructed in plasma from a given patient with renal failure and used to calculate that patient's values, or in a renal failure plasma pool and used to calculate all renal failure values, norepinephrine and epinephrine concentrations were not significantly different from those calculated from internal standards. We conclude: (1) External standard curves constructed in plasma from a given patient with renal failure can be used to measure norepinephrine and epinephrine in plasma from that patient; further, external standards in a renal failure plasma pool can be used for assays in patients with end-stage renal failure receiving long-term dialysis. (2) Major COMT inhibitory activity is not present commonly if samples from patients with renal failure are excluded. Thus, it would appear that external standard curves constructed in normal plasma can be used to measure norepinephrine and epinephrine precisely in samples from persons who do not have renal failure

  11. Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

    Science.gov (United States)

    Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

    2016-01-01

    Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect

  12. Sink limitation induces the expression of multiple soybean vegetative lipoxygenase mRNAs while the endogenous jasmonic acid level remains low.

    Science.gov (United States)

    Bunker, T W; Koetje, D S; Stephenson, L C; Creelman, R A; Mullet, J E; Grimes, H D

    1995-08-01

    The response of individual members of the lipoxygenase multigene family in soybeans to sink deprivation was analyzed. RNase protection assays indicated that a novel vegetative lipoxygenase gene, vlxC, and three other vegetative lipoxygenase mRNAs accumulated in mature leaves in response to a variety of sink limitations. These data suggest that several members of the lipoxygenase multigene family are involved in assimilate partitioning. The possible involvement of jasmonic acid as a signaling molecule regulating assimilate partitioning into the vegetative storage proteins and lipoxygenases was directly assessed by determining the endogenous level of jasmonic acid in leaves from plants with their pods removed. There was no rise in the level of endogenous jasmonic acid coincident with the strong increase in both vlxC and vegetative storage protein VspB transcripts in response to sink limitation. Thus, expression of the vegetative lipoxygenases and vegetative storage proteins is not regulated by jasmonic acid in sink-limited leaves.

  13. Endogenous fertility and development traps with endogenous lifetime

    OpenAIRE

    Fanti, Luciano; Gori, Luca

    2010-01-01

    We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004) and Bunzel and Qiao (2005) to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

  14. Effect of atropine, norepinephrine and phenylephrine on cerebral oxygenation and cardiac output during anesthesia.

    NARCIS (Netherlands)

    Kalmar, A.F.; Poterman, Marieke; Mooyaart, E.A.; Struys, Michel; Scheeren, Thomas

    2012-01-01

    Background:  Induction of general anesthesia often induces unwanted hypotension which is commonly treated with vasoactive medication to restore an appropriate blood pressure. Phenylephrine, norepinephrine and atropine are commonly used agents for this purpose with different physiological effects.

  15. Inhibition of K+ permeability diminishes alpha 2-adrenoceptor mediated effects on norepinephrine release

    International Nuclear Information System (INIS)

    Zimanyi, I.; Folly, G.; Vizi, E.S.

    1988-01-01

    The effect of two different potassium channel blockers, 4-aminopyridine (4-AP) and quinine, on the alpha 2-adrenoceptor mediated modulation of norepinephrine (NE) release was investigated. Pairs of mouse vasa deferentia were loaded with 3 H-norepinephrine ( 3 H-NE), superfused continuously, and stimulated electrically. 4-AP (5.3 x 10(-4) M), and quinine (10(-5) M) enhanced the stimulation-evoked release of tritium significantly. The electrically induced release of radioactivity was reduced by alpha 2-adrenoceptor agonists (1-NE and xylazine) and enhanced by the alpha 2-adrenoceptor antagonist yohimbine. Both effects were affected markedly by 4-AP or quinine: the depressant action of 1-NA and xylazine was partially antagonized and the facilitatory effect of yohimbine was completely abolished during the blockade of the potassium channels. It is suggested that the blockade of the potassium permeability counteracts negative feedback modulation; therefore, it seems likely that the stimulation of alpha 2-adrenoceptors leads to an enhanced potassium permeability and hyperpolarization of varicose axon terminals

  16. Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes

    Directory of Open Access Journals (Sweden)

    Niggemann Bernd

    2009-12-01

    Full Text Available Abstract Background Neurotransmitters are important regulators of the immune system, with very distinct and varying effects on different leukocyte subsets. So far little is known about the impact of signals mediated by neurotransmitters on the function of CD8+ T lymphocytes. Therefore, we investigated the influence of norepinephrine, dopamine and substance P on the key tasks of CD8+ T lymphocytes: activation, migration, extravasation and cytotoxicity. Results The activation of naïve CD8+ T lymphocytes by CD3/CD28 cross-linking was inhibited by norepinephrine and dopamine, which was caused by a downregulation of interleukin (IL-2 expression via Erk1/2 and NF-κB inhibition. Furthermore, all of the investigated neurotransmitters increased the spontaneous migratory activity of naïve CD8+ T lymphocytes with dopamine being the strongest inducer. In contrast, activated CD8+ T lymphocytes showed a reduced migratory activity in the presence of norepinephrine and substance P. With regard to extravasation we found norepinephrine to induce adhesion of activated CD8+ T cells: norepinephrine increased the interleukin-8 release from endothelium, which in turn had effect on the activated CXCR1+ CD8+ T cells. At last, release of cytotoxic granules from activated cells in response to CD3 cross-linking was not influenced by any of the investigated neurotransmitters, as we have analyzed by measuring the β-hexosamidase release. Conclusion Neurotransmitters are specific modulators of CD8+ T lymphocytes not by inducing any new functions, but by fine-tuning their key tasks. The effect can be either stimulatory or suppressive depending on the activation status of the cells.

  17. Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis.

    Science.gov (United States)

    Boyle, Peter; Koechlin, Alice; Bota, Maria; d'Onofrio, Alberto; Zaridze, David G; Perrin, Paul; Fitzpatrick, John; Burnett, Arthur L; Boniol, Mathieu

    2016-11-01

    To review and quantify the association between endogenous and exogenous testosterone and prostate-specific antigen (PSA) and prostate cancer. Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective cohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity. Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I² = 0%). Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI 0.30; 2.50). Results were consistent across studies. Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  18. Blood ketone response to norepinephrine-induced free fatty acid in diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Blackard, W G; Omori, Yoshiaki

    1963-04-18

    During 90-minute norepinephrine infusions, blood free fatty acid and ketone responses of Japanese nondiabetic and diabetic subjects were determined. Nonobese diabetic subjects with and without fasting hyperglycemia demonstrated significantly greater blood ketone elevations than nondiabetics. An inverse correlation between obesity and blood ketone response to nonrepinephrine was observed in diabetics. This correlation could not be attributed to varying degrees of fasting hyperglycemia or free fatty acid elevation. Nonobese diabetics with mild fasting hyperglycemia (90 to 150 mg%) exhibited an unexpected greater increase in blood ketones than nonobese diabetics with moderate fasting hyperglycemia (150 to 250 mg%). Differences in free fatty acid elevations were not responsible for this apparent paradox. The magnitude of the hyperketonemic response, though dependent on free fatty elevation, seemed more sensitive to the degree of obesity and the fasting blood glucose level. Fractional ketone body measurements attributed the blood ketone elevations predominantly to ..beta..-hydroxybutyric acid increases. 43 references, 6 figures, 1 table.

  19. Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: Ethylene oxide.

    Science.gov (United States)

    Kirman, C R; Hays, S M

    2017-12-01

    An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Iatrogenic Takotsubo Cardiomyopathy Secondary to Norepinephrine by Continuous Infusion for Shock

    OpenAIRE

    Alfredo Vieira; Bárbara Batista; Tiago Tribolet de Abreu

    2018-01-01

    Takotsubo cardiomyopathy is a condition characterized by transient left ventricular systolic and diastolic dysfunction, with a possible direct causal role of catecholamine in its pathophysiology. We present a case of a woman with shock and adrenal insufficiency in whom Takotsubo cardiomyopathy developed after treatment with norepinephrine. This case confirms the direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. An 82-year-old woman presented with asthenia...

  1. Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

    Science.gov (United States)

    Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping

    2014-01-01

    Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

  2. Monocular channels have a functional role in endogenous orienting.

    Science.gov (United States)

    Saban, William; Sekely, Liora; Klein, Raymond M; Gabay, Shai

    2018-03-01

    The literature has long emphasized the role of higher cortical structures in endogenous orienting. Based on evolutionary explanation and previous data, we explored the possibility that lower monocular channels may also have a functional role in endogenous orienting of attention. Sensitive behavioral manipulation was used to probe the contribution of monocularly segregated regions in a simple cue - target detection task. A central spatially informative cue, and its ensuing target, were presented to the same or different eyes at varying cue-target intervals. Results indicated that the onset of endogenous orienting was apparent earlier when the cue and target were presented to the same eye. The data provides converging evidence for the notion that endogenous facilitation is modulated by monocular portions of the visual stream. This, in turn, suggests that higher cortical mechanisms are not exclusively responsible for endogenous orienting, and that a dynamic interaction between higher and lower neural levels, might be involved. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Increased norepinephrine release from dog pulmonary artery caused by nitrous oxide

    International Nuclear Information System (INIS)

    Rorie, D.K.; Tyce, G.M.; Sill, J.C.

    1986-01-01

    The effects of nitrous oxide on the release and metabolism of norepinephrine (NE) at neuroeffector junctions in dog pulmonary artery were examined. Helical strips of artery were incubated in Krebs-Ringer solution containing L-( 3 H)NE and mounted for superfusion. The arterial strips were studied in the presence of 95% oxygen-5% carbon dioxide, 70% nitrogen-30% oxygen, or 70% nitrous oxide-30% oxygen. During the 60 min of each experiment, five samples of superfusion fluid were collected for analysis and the effluxes of ( 3 H)NE and its radiolabeled metabolites were measured before and during electrical stimulation and during recovery from stimulation. ( 3 H)Norepinephrine was separated from its metabolites in the superfusate and in extracts of artery by column chromatography and quantitated by liquid scintillation spectrometry. Nitrous oxide significantly increased the fractional loss of total radioactivity and the amount of NE in the superfusate both during resting conditions and during stimulation. Nitrous oxide had no effect on the proportions of radioactivity among metabolites of NE in the superfusate or on the profile of NE metabolites remaining in the tissue after experimentation. These findings are consistent with increased NE release as a direct effect of nitrous oxide on nerve endings

  4. The usefulness of cytogenetic parameters, level of p53 protein and endogenous glutathione as intermediate end-points in raw betel-nut genotoxicity.

    Science.gov (United States)

    Kumpawat, K; Chatterjee, A

    2003-07-01

    Betel-nut (BN) chewing related oral mucosal lesions are potential hazards to a large population worldwide. Genotoxicity of betel alkaloids, polyphenol and tannin fractions have been reported. It has been shown earlier that BN ingredients altered the level of endogenous glutathione (GSH) which could modulate the host susceptibility to the action of other chemical carcinogens. The north-east Indian variety of BN, locally known as 'kwai', is raw, wet and consumed unprocessed with betel-leaf and slaked lime and contains higher alkaloids, polyphenol and tannins as compared to the dried one. Therefore, the purpose of this study was to investigate the extent of DNA damage, pattern of cell kinetics, the level of p53-protein and endogenous GSH in kwai chewers in the tribal population of Meghalaya state in the northeastern region of India with an aim to see whether these end-points could serve as biomarkers of genetic damage of relevance for genotoxic/carcinogenic process. The present data show higher DNA damage, delay in cell kinetics, p53 expression and lower GSH-level in heavy chewers (HC) than nonchewers (NC). The influence of bleomycin (BLM) on chromatid break induction in G2-phase of peripheral blood lymphocytes in NC and HC has been analysed to determine individual susceptibility to carcinogenic assaults. HC showed higher induction of chromatid breaks than NC. Risk assessment in this study suggests an interaction between carcinogen exposure and mutagen sensitivity measures, risk estimates being higher in those individuals who both consume kwai and express sensitivity to free radical oxygen damage in vitro. From this study it seems that besides cytogenetical parameters, the level of endogenous GSH and the level of p53 protein could act as effective biomarkers for kwai chewers.

  5. Analytical Strategies for the Determination of Norepinephrine Reuptake Inhibitors in Pharmaceutical Formulations and Biological Fluids.

    Science.gov (United States)

    Saka, Cafer

    2016-01-01

    Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review.

  6. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

    2018-04-01

    This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

  7. Effects of norepinephrine on tissue perfusion in a sheep model of intra-abdominal hypertension

    NARCIS (Netherlands)

    Ferrara, Gonzalo; Kanoore Edul, Vanina S.; Caminos Eguillor, Juan F.; Martins, Enrique; Canullán, Carlos; Canales, Héctor S.; Ince, Can; Estenssoro, Elisa; Dubin, Arnaldo

    2015-01-01

    The aim of the study was to describe the effects of intra-abdominal hypertension (IAH) on regional and microcirculatory intestinal blood flow, renal blood flow, and urine output, as well as their response to increases in blood pressure induced by norepinephrine. This was a pilot, controlled study,

  8. Invasive fungal infections in endogenous Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Selbach Scheffel

    2010-06-01

    Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

  9. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  10. Influence of allelic variations in relation to norepinephrine and mineralocorticoid receptors on psychopathic traits: a pilot study

    Directory of Open Access Journals (Sweden)

    Guillaume Durand

    2018-03-01

    Full Text Available Background Past findings support a relationship between abnormalities in the amygdala and the presence of psychopathic traits. Among other genes and biomarkers relevant to the amygdala, norepinephrine and mineralocorticoid receptors might both play a role in psychopathy due to their association with traits peripheral to psychopathy. The purpose is to examine if allelic variations in single nucleotide polymorphisms related to norepinephrine and mineralocorticoid receptors play a role in the display of psychopathic traits and executive functions. Methods Fifty-seven healthy participants from the community provided a saliva sample for SNP sampling of rs5522 and rs5569. Participants then completed the Psychopathic Personality Inventory–Short Form (PPI-SF and the Tower of Hanoi. Results Allelic variations of both rs5522 and rs5569 were significant when compared to PPI-SF total score and the fearless dominance component of the PPI-SF. A significant result was also obtained between rs5522 and the number of moves needed to complete the 5-disk Tower of Hanoi. Conclusion This pilot study offers preliminary results regarding the effect of allelic variations in SNPs related to norepinephrine and mineralocorticoid receptors on the presence of psychopathic traits. Suggestions are provided to enhance the reliability and validity of a larger-scale study.

  11. Fast-scan cyclic voltammetry (FSCV) detection of endogenous octopamine in Drosophila melanogaster ventral nerve cord

    Science.gov (United States)

    Pyakurel, Poojan; Privman, Eve; Venton, B. Jill

    2016-01-01

    Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. An FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval VNC. Repeated stimulations were stable with 2 or 5 minutes interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain. PMID:27326831

  12. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  13. Fluctuating Estrogen and Progesterone Receptor Expression in Brainstem Norepinephrine Neurons through the Rat Estrous Cycle

    NARCIS (Netherlands)

    Haywood, S.A.; Simonian, S.X.; Beek, van der E.M.; Bicknell, R.J.; Herbison, A.E.

    1999-01-01

    Norepinephrine (NE) neurons within the nucleus tractus solitarii (NTS; A2 neurons) and ventrolateral medulla (A1 neurons) represent gonadal steroid-dependent components of several neural networks regulating reproduction. Previous studies have shown that both A1 and A2 neurons express estrogen

  14. Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans

    DEFF Research Database (Denmark)

    Astrup, A; Andersen, T; Christensen, N J

    1990-01-01

    A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower...... in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose...... was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may...

  15. Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

    2011-05-19

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  16. The Endogenous Exposome

    Science.gov (United States)

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  17. Production of endogenous pyrogen.

    Science.gov (United States)

    Dinarello, C A

    1979-01-01

    The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

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

    OpenAIRE

    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, res...

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

    Science.gov (United States)

    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.

  20. Effects of cocaine on [11C]norepinephrine and [11C]β-CIT uptake in the primate peripheral organs measured by PET

    International Nuclear Information System (INIS)

    Suhara, Tetsuya; Farde, L.; Halldin, C.; Karlsson, P.; Nagren, K.

    1996-01-01

    The toxic properties of cocaine are related to both the central and peripheral effects. To identify possible lethal mechanisms and the accumulation of cocaine in various organs, the effects of cocaine on [ 11 C] norepinephrine and cocaine congener [ 11 C]β-CIT uptake in Cynomolgus monkeys were measured by positron emission tomography (PET). Cocaine (5 mg/kg) noticeably inhibited [ 11 C] norepinephrine uptake in the heart. The uptake of [ 11 C]β-CIT in the heart and lung was reduced by pretreatment with cocaine. There was a significant uptake in the liver which was increased following cocaine pretreatment. The results of this study confirm that cocaine blocks the neuronal uptake of norepinephrine in sympathetic nerve terminals in the myocardium. The effect of cocaine on [ 11 C]β-CIT uptake indicates that the binding sites in the heart and lung are saturable, while the uptake mechanism in the liver is different from those of the heart and lung. (author)

  1. Lidocaine attenuates anisomycin-induced amnesia and release of norepinephrine in the amygdala

    Science.gov (United States)

    Sadowski, Renee N.; Canal, Clint E.; Gold, Paul E.

    2011-01-01

    When administered near the time of training, protein synthesis inhibitors such as anisomycin impair later memory. A common interpretation of these findings is that memory consolidation requires new protein synthesis initiated by training. However, recent findings support an alternative interpretation that abnormally large increases in neurotransmitter release after injections of anisomycin may be responsible for producing amnesia. In the present study, a local anesthetic was administered prior to anisomycin injections in an attempt to mitigate neurotransmitter actions and thereby attenuate the resulting amnesia. Rats received lidocaine and anisomycin injections into the amygdala 130 and 120 min, respectively, prior to inhibitory avoidance training. Memory tests 48 hr later revealed that lidocaine attenuated anisomycin-induced amnesia. In other rats, in vivo microdialysis was performed at the site of amygdala infusion of lidocaine and anisomycin. As seen previously, anisomycin injections produced large increases in release of norepinephrine in the amygdala. Lidocaine attenuated the anisomycin-induced increase in release of norepinephrine but did not reverse anisomycin inhibition of protein synthesis, as assessed by c-Fos immunohistochemistry. These findings are consistent with past evidence suggesting that anisomycin causes amnesia by initiating abnormal release of neurotransmitters in response to the inhibition of protein synthesis. PMID:21453778

  2. Stress hormone epinephrine (adrenaline) and norepinephrine (noradrenaline) effects on the anaerobic bacteria.

    Science.gov (United States)

    Boyanova, Lyudmila

    2017-04-01

    Microbial endocrinology is a relatively new research area that already encompasses the anaerobes. Stress hormones, epinephrine and norepinephrine, can affect the growth of anaerobic bacteria such as Fusobacterium nucleatum, Prevotella spp., Porhyromonas spp., Tanerella forsythia and Propionibacterium acnes and can increase virulence gene expression, iron acquisition and many virulence factors of some anaerobic species such as Clostridium perfringens, Porphyromonas gingivalis and Brachyspira pilosicoli. Epinephrine and norepinephrine effects can lead to a growth increase or decrease, or no effect on the growth of the anaerobes. The effects are species-specific and perhaps strain-specific. Discrepancies in the results of some studies can be due to the different methods and media used, catecholamine concentrations, measurement techniques and the low number of strains tested. Biological effects of the stress hormones on the anaerobes may range from halitosis and a worsening of periodontal diseases to tissue damages and atherosclerotic plaque ruptures. Optimizations of the research methods and a detailed assessment of the catecholamine effects in conditions mimicking those in affected organs and tissues, as well as the effects on the quorum sensing and virulence of the anaerobes and the full spectrum of biological consequences of the effects are interesting topics for further evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Feeding Releases Endogenous Opioids in Humans.

    Science.gov (United States)

    Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

    2017-08-23

    The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

  4. Effects of soil drought stress on plant regeneration efficiency and endogenous hormone levels of immature embryos in wheat (Triticum aestivum L.)

    International Nuclear Information System (INIS)

    Bie, X.; Wang, K.; Liu, C.; Du, L.

    2017-01-01

    In this study, the water supply in soil for wheat mother donor plants was controlled, leading to drought stress conditions, and the relative soil water content (RSWC) was measured in different soil depths. The immature embryos of common wheat (Triticum aestivum L.) 13 days post anthesis (DPA) were used to test regeneration capacity. The accumulation of the plant growth regulators (PGRs) including abscisic acid (ABA), indole-3-acetic acid (IAA), and hydrogen peroxide (H2O2) in the wheat embryos grown under the two conditions was measured. The results indicated that RSWC difference between the drought treatment and the irrigated control was more than 13% at the various soil depths, with the maximum difference was observed at 40 cm depth. Tissue culture evaluation showed that the plant regeneration efficiency of the immature embryos grown under drought stress treatment was significantly higher than that of the tissues grown under the control condition. Assay for PGR found that the drought stress caused obviously increased concentration of endogenous ABA and H2O2, and slightly decreased level of IAA in the target tissues. Therefore, it seems that the concentration of endogenous ABA, IAA, and H2O2 in immature wheat embryos is very important in regeneration capacity. Drought stress can improve the regeneration capacity by changing the levels of ABA, IAA, and H2O2. Our results would be helpful to efficient development of genetically modified wheat plants through improvement of regeneration via manipulating the endogenous PGRs. (author)

  5. Endogenous Locus Reporter Assays.

    Science.gov (United States)

    Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

    2018-01-01

    Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

  6. The role of serotonin and norepinephrine in sleep-waking activity.

    Science.gov (United States)

    Morgane, P J; Stern, W C

    1975-11-01

    A critical review of the evidences relating the biogenic amines serotonin and norepinephrine to the states of slow-wave and rapid eye movement (REM) sleep is presented. Various alternative explanations for specific chemical regulation of the individual sleep states, including the phasic events of REM sleep, are evaluated within the overall framework of the monoamine theory of sleep. Several critical neuropsychopharmacological studies relating to metabolsim of the amines in relation to sleep-waking behavior are presented. Models of the chemical neuronal circuitry involved in sleep-waking activity are derived and interactions between several brainstem nuclei, particularly the raphé complex and locus coeruleus, are discussed. Activity in these aminergic systems in relation to oscillations in the sleep-waking cycles is evaluated. In particular, the assessment of single cell activity in specific chemical systems in relations to chemical models of sleep is reviewed. Overall, it appears that the biogenic amines, especially serotonin and norepinephrine, play key roles in the generation and maintenance of the sleep states. These neurotransmitters participate in some manner in the "triggering" processes necessary for actuating each sleep phase and in regulating the transitions from sleep to waking activity. The biogenic amines are, however, probably not "sleep factors" or direct inducers of the sleep states. Rather, they appear to be components of a multiplicity of interacting chemical circuitry in the brain whose activity maintains various chemical balances in different brain regions. Shifts in these balances appear to be involved in the triggering and maintenance of the various states comprising the vigilance continuum.

  7. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand.

    Science.gov (United States)

    Reis, António M C; Mills, Wilbur K; Ramachandran, Ilangovan; Friedberg, Errol C; Thompson, David; Queimado, Lurdes

    2012-01-01

    Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process.

  8. Proteomics investigation of endogenous S-nitrosylation in Arabidopsis

    International Nuclear Information System (INIS)

    Fares, Abasse; Rossignol, Michel; Peltier, Jean-Benoît

    2011-01-01

    Highlights: ► Identification and quantification of nitrosothiols. ► A first dataset of endogenously nitrosylated cysteines in Arabidopsis cells. ► Nitrosothiols display apolar motifs not located in close vicinity of cysteines. ► Salt stress alters the endogenous nitrosylation of specific cysteines in Arabidopsis. -- Abstract: S-Nitrosylation emerges as an important protein modification in many processes. However, most data were obtained at the protein level after addition of a NO donor, particularly in plants where information about the cysteines nitrosylated in these proteins is scarce. An adapted work-flow, combining the classical biotin switch method and labeling with isotope-coded affinity tags (ICAT), is proposed. Without addition of NO donor, a total of 53 endogenous nitrosocysteines was identified in Arabidopsis cells, in proteins belonging to all cell territories, including membranes, and covering a large panel of functions. This first repertoire of nitrosothiols in plants enabled also preliminary structural description. Three apolar motifs, not located in close vicinity of cysteines and accounting for half the dataset, were detected and are proposed to complement nitrosylation prediction algorithms, poorly trained with plant data to date. Analysis of changes induced by a brief salt stress showed that NaCl modified the nitrosylation level of a small proportion of endogenously nitrosylated proteins and did not concern all nitrosothiols in these proteins. The possible role of some NO targets in the response to salt stress was discussed.

  9. Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

    Science.gov (United States)

    Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

    2015-12-01

    Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

  10. Dietary counselling effectively improves lipid levels in patients with endogenous hypertriglyceridemia: emphasis on weight reduction and alcohol limitation

    NARCIS (Netherlands)

    de Man, F. H.; van der Laarse, A.; Hopman, E. G.; Gevers Leuven, J. A.; Onkenhout, W.; Dallinga-Thie, G. M.; Smelt, A. H.

    1999-01-01

    To evaluate the short-term effect of dietary counselling in patients with endogenous hypertriglyceridemia and evaluate the effects of advised nutrient changes. A prospective dietary intervention study in patients with endogenous hypertriglyceridemia from January I st 1988 to December 31 st 1996

  11. Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia : A randomised controlled trial

    NARCIS (Netherlands)

    Poterman, Marieke; Vos, Jaap Jan; Vereecke, Hugo E. M.; Struys, Michel M. R. F.; Vanoverschelde, Henk; Scheeren, Thomas W. L.; Kalmar, Alain F.

    BACKGROUND Phenylephrine and norepinephrine are two vasopressors commonly used to counteract anaesthesia-induced hypotension. Their dissimilar working mechanisms may differentially affect the macro and microcirculation, and ultimately tissue oxygenation. OBJECTIVES We investigated the differential

  12. Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

    Directory of Open Access Journals (Sweden)

    Fitzgerald PJ

    2012-06-01

    Full Text Available Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: There is growing evidence that the neurotransmitter norepinephrine (NE and its sister molecule epinephrine (EPI (adrenaline affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically, and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.Keywords: clonidine, guanfacine, aspirin, acetylcholine, epinephrine, adrenaline, sympathetic nervous system, parasympathetic nervous system, inflammation

  13. [Significance of endogenous sulfur dioxide in the regulation of cardiovascular system].

    Science.gov (United States)

    Jin, Hong Fang; DU, Shu Xu; Zhao, Xia; Zhang, Su Qing; Tian, Yue; Bu, Ding Fang; Tang, Chao Shu; DU, Jun Bao

    2007-08-18

    Since the 1980's nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO(2)) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to beta-sulfinyl pyruvate which decomposes spontaneously to pyruvate and SO(2). In mammals, activated neutrophils by oxidative stress can convert H(2)S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO(2) in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO(2) content. As the key enzyme producing SO(2), GOT mRNA in cardiovascular system was detected and found to be located enriched in endothelial cells and vascular smooth muscle cells near the endothelial layer. When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO(2) level in the rats injected with 125 micromol/kg body weight SO(2) donor was

  14. Endogenous Prospect Theory

    OpenAIRE

    Schmidt, Ulrich; Zank, Horst

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This paper provides an axiomatization of a new specification of cumulative prospect theory, termed endogenous prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  15. Pathogenesis of fever: effects of various endogenous pyrogens upon the level of circulating granulocytes in normal rabbits.

    Science.gov (United States)

    KING, M K

    1960-11-01

    The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed.

  16. Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress.

    Science.gov (United States)

    Skosnik, P D; Chatterton, R T; Swisher, T; Park, S

    2000-04-01

    Two of the most salient physiological responses to stress are increased norepinephrine (NE) and cortisol (CORT) activities. However, it is unclear how these neurochemical events affect cognition, especially attention. We examined the effects of mild psychological stress on selective attention, as assessed by the negative priming (NP) paradigm. Salivary measures of the stress hormone CORT and alpha-amylase (a correlate of NE) were assayed to probe the relationship between the stress response and attentional inhibition. Healthy subjects (N = 20) engaged in the attention task, which was then followed by 15 min of a stressful video game before a return to the attentional task. Baseline saliva samples were obtained before the experiment began, 1 min after the video-game stressor, and 20 min post-stress. Subjects showed a significant reduction in NP and a decrease in reaction time (RT) after the video game. Moreover, alpha-amylase levels increased significantly after the stressor, indicating the role of NE in the acute stress response. While CORT levels remained unchanged after stress, CORT correlated significantly with both NP scores and RT after the stressor. These results imply that mild psychological stress can significantly alter attentional processes. Given the increase in alpha-amylase and the correlation between attention and CORT after stress, it seems likely that attentional processes are under tight control by brain systems which mediate the fight-or-flight response.

  17. Effect of pinacidil on norepinephrine- and potassium-induced contractions and membrane potential in rat and human resistance vessels and in rat aorta

    International Nuclear Information System (INIS)

    Videbaek, L.M.; Aalkjaer, C.; Mulvany, M.J.

    1988-01-01

    The effect of pinacidil on contractile responses to norepinephrine, potassium, and membrane potential was examined in rat and human resistance vessels. In some experiments rat aorta was also used. Pinacidil (0.1-30 microM) caused a concentration-dependent relaxation of norepinephrine-induced contractions in all vessels studied. In the same concentration range, pinacidil had only little effect on potassium (125 mM) activated rat mesenteric and femoral resistance vessels. In denervated rat mesenteric resistance vessels, a depolarization with potassium (125 mM) before superimposing a norepinephrine tone markedly diminished the effect of pinacidil. In resting rat mesenteric resistance vessels, pinacidil (1-10 microM) caused a hyperpolarization of 10-15 mV. In rat aorta, pinacidil (10 microM) caused a significant (p less than 0.001) increase in 86 Rb+ efflux rate constant whereas 1 microM had no effect. The results of these experiments indicate that the vasodilating effect may be caused by a hyperpolarization of the vascular smooth muscle cell membrane

  18. Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

    Science.gov (United States)

    Stefanovic, Bojana; Spasojevic, Natasa; Jovanovic, Predrag; Jasnic, Nebojsa; Djordjevic, Jelena; Dronjak, Sladjana

    2016-10-01

    The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  19. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  20. Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs.

    Science.gov (United States)

    Smith, Samson W; Latta, Leigh C; Denver, Dee R; Estes, Suzanne

    2014-07-24

    The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory.

  1. Orienting of attention, pupil size, and the norepinephrine system.

    Science.gov (United States)

    Gabay, Shai; Pertzov, Yoni; Henik, Avishai

    2011-01-01

    This research examined a novel suggestion regarding the involvement of the locus coeruleus-norepinephrine (LC-NE) system in orienting reflexive (exogenous) attention. A common procedure for studying exogenous orienting of attention is Posner's cuing task. Importantly, one can manipulate the required level of target processing by changing task requirements, which, in turn, can elicit a different time course of inhibition of return (IOR). An easy task (responding to target location) produces earlier onset IOR, whereas a demanding task (responding to target identity) produces later onset IOR. Aston-Jones and Cohen (Annual Review of Neuroscience, 28, 403-450, 2005) presented a theory suggesting two different modes of LC activity: tonic and phasic. Accordingly, we suggest that in the more demanding task, the LC-NE system is activated in phasic mode, and in the easier task, it is activated in tonic mode. This, in turn, influences the appearance of IOR. We examined this suggestion by measuring participants' pupil size, which has been demonstrated to correlate with the LC-NE system, while they performed cuing tasks. We found a response-locked phasic dilation of the pupil in the discrimination task, as compared with the localization task, which may reflect different firing modes of the LC-NE system during the two tasks. We also demonstrated a correlation between pupil size at the time of cue presentation and magnitude of IOR.

  2. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

    Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

  3. [Dynamic hierarchy of regulatory peptides. Structure of the induction relations of regulators as the target for therapeutic agents].

    Science.gov (United States)

    Koroleva, S V; Miasoedov, N F

    2012-01-01

    Based on the database information (literature period 1970-2010 gg.) on the effects of regulatory peptides (RP) and non-peptide neurotransmitters (dopamine, serotonin, norepi-nephrine, acetylcholine) it was analyzed of possible cascade processes of endogenous regulators. It was found that the entire continuum of RP and mediators is a chaotic soup of the ordered three-level compartments. Such a dynamic functional hierarchy of endogenous regulators allows to create start-up and corrective tasks for a variety of physiological functions. Some examples of static and dynamic patterns of induction processes of RP and mediators (that regulate the states of anxiety, depression, learning and memory, feeding behavior, reproductive processes, etc.) are considered.

  4. Anxiety-induced plasma norepinephrine augmentation increases reactive oxygen species formation by monocytes in essential hypertension.

    Science.gov (United States)

    Yasunari, Kenichi; Matsui, Tokuzo; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Kiriike, Nobuo

    2006-06-01

    An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect. In Protocol 1, a cross-sectional study was performed in 146 hypertensive patients to evaluate whether anxiety and depression affect BP and ROS formation by MNC through increasing plasma catecholamines. In Protocol 2, a 6-month randomized controlled trial using a subtherapeutic dose of the alpha(1)-adrenergic receptor antagonist doxazosin (1 mg/day) versus placebo in 86 patients with essential hypertension was performed to determine whether the increase in ROS formation by MNC was independent of BP. In Protocol 1, a significant relationship was observed between the following: trait anxiety and plasma norepinephrine (r = 0.32, P anxiety may increase plasma norepinephrine and increase ROS formation by MNC independent of BP in hypertensive patients.

  5. Acute myocardial infarction without significant coronary stenoses associated with endogenous subclinical hyperthyroidism.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

    2012-04-05

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. Nowadays, there is growing interest regarding endogenous sublinical hyperthyroidism and the cardiovascular system. We present a case of acute myocardial infarction without significant coronary stenoses in a 75-year-old Italian woman with endogenous subclinical hyperthyroidism. Also this case focuses attention on the importance of a correct evaluation of endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  6. Habits, aspirations and endogenous fertility

    OpenAIRE

    Luciano Fanti

    2012-01-01

    Motivated by the increasing literature on endogenous preferences as well as on endogenous fertility, this paper investigates the implications of the interaction of the endogenous determination of the number of children with habit and aspiration formation in an OLG model. In contrast with the previous literature, we show that greater aspirations may lead to higher savings, and more interestingly, always increase the neoclassical economic growth.

  7. Cerebellar Norepinephrine Modulates Learning of Delay Classical Eyeblink Conditioning: Evidence for Post-Synaptic Signaling via PKA

    Science.gov (United States)

    Fister, Mathew; Bickford, Paula C.; Cartford, M. Claire; Samec, Amy

    2004-01-01

    The neurotransmitter norepinephrine (NE) has been shown to modulate cerebellar-dependent learning and memory. Lesions of the nucleus locus coeruleus or systemic blockade of noradrenergic receptors has been shown to delay the acquisition of several cerebellar-dependent learning tasks. To date, no studies have shown a direct involvement of…

  8. Endogenous jasmonic and salicylic acids levels in the Cd-hyperaccumulator Noccaea (Thlaspi) praecox exposed to fungal infection and/or mechanical stress.

    Science.gov (United States)

    Llugany, M; Martin, S R; Barceló, J; Poschenrieder, C

    2013-08-01

    Sensitivity to Erysiphe in Noccaea praecox with low metal supply is related to the failure in enhancing SA. Cadmium protects against fungal-infection by direct toxicity and/or enhanced fungal-induced JA signaling. Metal-based defense against biotic stress is an attractive hypothesis on evolutionary advantages of plant metal hyperaccumulation. Metals may compensate for a defect in biotic stress signaling in hyperaccumulators (metal-therapy) by either or both direct toxicity to pathogens and by metal-induced alternative signaling pathways. Jasmonic acid (JA) and salicylic acid (SA) are well-established components of stress signaling pathways. However, few studies evaluate the influence of metals on endogenous concentrations of these defense-related hormones. Even less data are available for metal hyperaccumulators. To further test the metal-therapy hypothesis we analyzed endogenous SA and JA concentrations in Noccaea praecox, a cadmium (Cd) hyperaccumulator. Plants treated or not with Cd, were exposed to mechanical wounding, expected to enhance JA signaling, and/or to infection by biotrophic fungus Erysiphe cruciferarum for triggering SA. JA and SA were analyzed in leaf extracts using LC-ESI(-)-MS/MS. Plants without Cd were more susceptible to fungal attack than plants receiving Cd. Cadmium alone tended to increase leaf SA but not JA. Either or both fungal attack and mechanical wounding decreased SA levels and enhanced JA in the Cd-rich leaves of plants exposed to Cd. High leaf Cd in N. praecox seems to hamper biotic-stress-induced SA, while triggering JA signaling in response to fungal attack and wounding. To the best of our knowledge, this is the first report on the endogenous JA and SA levels in a Cd-hyperaccumulator exposed to different biotic and abiotic stresses. Our results support the view of a defect in SA stress signaling in Cd hyperaccumulating N. praecox.

  9. Idle behaviors of the hippocampus reflect endogenous cortisol levels in youth.

    Science.gov (United States)

    Thomason, Moriah E; Tocco, Maria A; Quednau, Kelly A; Bedway, Andrea R; Carré, Justin M

    2013-06-01

    Compelling evidence indicates that disruption in functional connectivity (FC) in brain networks underlies many psychiatric and developmental disorders. Current theory posits that biological (i.e., cortisol) and environmental (i.e., stress) experiences in early life are strong determinants in the development of functional brain systems and formative in the genesis of such disorders. The objective of this study was to examine the extent to which individual differences in cortisol concentrations during FC magnetic resonance imaging (MRI) would map onto variability in hippocampal to default mode network (DMN) connectivity in typically developing youth. Salivary cortisol and FC MRI data were collected concurrently in 33 scan-naive 7- to 15-year-old participants. Twenty-nine of these participants previously completed the Trier Social Stress Test. Hippocampal to DMN FC and endogenous cortisol variability during MRI were examined. A possible association between MRI cortisol and cortisol response to the Trier Social Stress Test during the preceding visit or a participant's ratings of anxiety during MRI was tested. There were significant positive relations between MRI cortisol levels and measurements in the following 3 areas: hippocampal to DMN FC during the resting state, cortisol levels during the Trier Social Stress Test, and fear/anxiety ratings during MRI. Fear/anxiety ratings during MRI also related to self-reported anxiety on standardized measurements. This study shows for the first time that FC of the hippocampus is altered with changing cortisol responsivity in youth. Altered FC during the resting state may represent altered alertness or monitoring resulting from variation in glucocorticoid function in youth, which carries implications for the effect of stress on response monitoring and decision making. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Endogenous lycopene improves ethanol production under acetic acid stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Pan, Shuo; Jia, Bin; Liu, Hong; Wang, Zhen; Chai, Meng-Zhe; Ding, Ming-Zhu; Zhou, Xiao; Li, Xia; Li, Chun; Li, Bing-Zhi; Yuan, Ying-Jin

    2018-01-01

    Acetic acid, generated from the pretreatment of lignocellulosic biomass, is a significant obstacle for lignocellulosic ethanol production. Reactive oxidative species (ROS)-mediated cell damage is one of important issues caused by acetic acid. It has been reported that decreasing ROS level can improve the acetic acid tolerance of Saccharomyces cerevisiae . Lycopene is known as an antioxidant. In the study, we investigated effects of endogenous lycopene on cell growth and ethanol production of S. cerevisiae in acetic acid media. By accumulating endogenous lycopene during the aerobic fermentation of the seed stage, the intracellular ROS level of strain decreased to 1.4% of that of the control strain during ethanol fermentation. In the ethanol fermentation system containing 100 g/L glucose and 5.5 g/L acetic acid, the lag phase of strain was 24 h shorter than that of control strain. Glucose consumption rate and ethanol titer of yPS002 got to 2.08 g/L/h and 44.25 g/L, respectively, which were 2.6- and 1.3-fold of the control strain. Transcriptional changes of INO1 gene and CTT1 gene confirmed that endogenous lycopene can decrease oxidative stress and improve intracellular environment. Biosynthesis of endogenous lycopene is first associated with enhancing tolerance to acetic acid in S. cerevisiae . We demonstrate that endogenous lycopene can decrease intracellular ROS level caused by acetic acid, thus increasing cell growth and ethanol production. This work innovatively   puts forward a new strategy for second generation bioethanol production during lignocellulosic fermentation.

  11. Host-virus interactions of mammalian endogenous retroviruses

    OpenAIRE

    Farkašová, Helena

    2017-01-01

    Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

  12. Reference intervals and variation for urinary epinephrine, norepinephrine and cortisol in healthy men and women in Denmark

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Garde, A H; Christensen, J M

    2001-01-01

    Reference intervals for urinary epinephrine, norepinephrine and cortisol in 120 healthy individuals performing their routine work were established according to the International Union of Pure and Applied Chemistry (IUPAC) and the International Federation of Clinical Chemistry and Laboratory...... Medicine (IFCC) for use in the risk assessment of exposure to occupational stress. Reference intervals were established for three different times of the day: in morning samples (05.45-07.15) the limit of detection (LOD) was 2.10 micromol epinephrine/mol creatinine (82 women) and 2.86 micromol epinephrine....../mol creatinine (37 men), and the reference interval was 3.6-29.1 micromol norepinephrine/mol creatinine and 2.3-52.8 micromol cortisol/mol creatinine (119 women and men); in afternoon samples (15.30-18.30) the reference interval was 0.64-10.8 micromol epinephrine/mol creatinine (82 women), 1.20-11.2 micromol...

  13. Endogenous Monetary Policy Regime Change

    OpenAIRE

    Troy Davig; Eric M. Leeper

    2006-01-01

    This paper makes changes in monetary policy rules (or regimes) endogenous. Changes are triggered when certain endogenous variables cross specified thresholds. Rational expectations equilibria are examined in three models of threshold switching to illustrate that (i) expectations formation effects generated by the possibility of regime change can be quantitatively important; (ii) symmetric shocks can have asymmetric effects; (iii) endogenous switching is a natural way to formally model preempt...

  14. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-01-01

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  15. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

    Science.gov (United States)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-10-15

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  16. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes.

    Science.gov (United States)

    Wu, Gong-Jhe; Chen, Tyng-Guey; Chang, Huai-Chia; Chiu, Wen-Ta; Chang, Chia-Chen; Chen, Ruei-Ming

    2007-08-15

    During inflammation, overproduction of nitric oxide (NO) can damage chondrocytes. In this study, we separately evaluated the toxic effects of exogenous and endogenous NO on human chondrocytes and their possible mechanisms. Human chondrocytes were exposed to sodium nitroprusside (SNP), an NO donor, or a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) as the exogenous and endogenous sources of NO, respectively. Administration of SNP or a combination of LPS and IFN-gamma in human chondrocytes increased cellular NO levels but decreased cell viability. Exposure to exogenous or endogenous NO significantly induced apoptosis of human chondrocytes. When treated with exogenous or endogenous NO, the mitochondrial membrane potential time-dependently decreased. Exposure to exogenous or endogenous NO significantly enhanced cellular reactive oxygen species (ROS) and cytochrome c (Cyt c) levels. Administration of exogenous or endogenous NO increased caspase-3 activity and consequently induced DNA fragmentation. Suppression of caspase-3 activation by Z-DEVD-FMK decreased NO-induced DNA fragmentation and cell apoptosis. Similar to SNP, exposure of human chondrocytes to S-nitrosoglutathione (GSNO), another NO donor, caused significant increases in Cyt c levels, caspase-3 activity, and DNA fragmentation, and induced cell apoptosis. Pretreatment with N-monomethyl arginine (NMMA), an inhibitor of NO synthase, significantly decreased cellular NO levels, and lowered endogenous NO-induced alterations in cellular Cyt c amounts, caspase-3 activity, DNA fragmentation, and cell apoptosis. Results of this study show that NO from exogenous and endogenous sources can induce apoptotic insults to human chondrocytes via a mitochondria-dependent mechanism.

  17. Voltammetric determination of norepinephrine in the presence of acetaminophen using a novel ionic liquid/multiwall carbon nanotubes paste electrode

    International Nuclear Information System (INIS)

    Salmanpour, Sadegh; Tavana, Toktam; Pahlavan, Ali; Khalilzadeh, Mohammad A.; Ensafi, Ali A.; Karimi-Maleh, Hassan; Beitollahi, Hadi; Kowsari, Elaheh; Zareyee, Daryoush

    2012-01-01

    A novel multiwall carbon nanotubes (MWCNTs) modified carbon ionic liquid electrode (CILE) was fabricated and used to investigate the electrochemical behavior of norepinephrine (NP). MWCNTs/CILE was prepared by mixing hydrophilic ionic liquid, 1-methyl-3-butylimidazolium bromide (MBIDZBr), with graphite powder, MWCNTs, and liquid paraffin. The fabricated MWCNTs/CILE showed great electrocatalytic ability to the oxidation of NE. The electron transfer coefficient, diffusion coefficient, and charge transfer resistant (R ct ) of NE at the modified electrode were calculated. Differential pulse voltammetry of NE at the modified electrode exhibited two linear dynamic ranges with slopes of 0.0841 and 0.0231 μA/μM in the concentration ranges of 0.3 to 30.0 μM and 30.0 to 450.0 μM, respectively. The detection limit (3σ) of 0.09 μM NP was achieved. This modified electrode exhibited a good ability for well separated oxidation peaks of NE and acetaminophen (AC) in a buffer solution, pH 7.0. The proposed sensor was successfully applied for the determination of NE in human urine, pharmaceutical, and serum samples. Highlights: ► Electrochemical behavior of norepinephrine study using carbon ionic liquid electrode ► This sensor resolved the overlap response of norepinephrine and acetaminophen. ► This sensor is also used for the determination of above compounds in real samples.

  18. Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

    Science.gov (United States)

    Brown, Susan B; Hankinson, Susan E

    2015-07-01

    Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Copyright © 2015

  19. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

    Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

  20. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  1. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    OpenAIRE

    GEAMĂNU MARINELA

    2012-01-01

    The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies. Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

  2. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Rachma, Meutia Safrina

    2011-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  3. Endogeneity Of Indonesian Money Supply

    OpenAIRE

    Rachma, Meutia Safrina

    2010-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  4. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

    Science.gov (United States)

    Hindle, Samantha J; Munji, Roeben N; Dolghih, Elena; Gaskins, Garrett; Orng, Souvinh; Ishimoto, Hiroshi; Soung, Allison; DeSalvo, Michael; Kitamoto, Toshihiro; Keiser, Michael J; Jacobson, Matthew P; Daneman, Richard; Bainton, Roland J

    2017-10-31

    Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Norepinephrine spillover from skeletal muscle during exercise in humans

    DEFF Research Database (Denmark)

    Savard, G K; Richter, Erik; Strange, S

    1989-01-01

    The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one...... legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise...... in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising...

  6. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  7. Comparison of psychological symptoms and serum levels of neurotransmitters in Shanghai adolescents with and without internet addiction disorder: a case-control study.

    Directory of Open Access Journals (Sweden)

    Hong-Xia Zhang

    Full Text Available BACKGROUND: Internet addiction disorder (IAD is now recognized internationally and is known to be linked with academic and social impairment. To date, we know little about its associated main biological factors. This study aimed to collect a carefully defined group of adolescents with IAD and an age- and gender-matched typically developing comparison group. We hypothesized that the young people with IAD would have higher rates of self-reported anxiety and depressive symptoms, have altered levels of peripheral blood dopamine, norepinephrine and serotonin. In addition, we hypothesized the hours spent online are correlated with the severity of depression and anxiety among these young people with IAD. METHODOLOGY/PRINCIPAL FINDING: A cross-sectional study of 20 adolescents who met Beard's criteria for IAD and 15 typically developing adolescents (comparison group was conducted. All the participants completed the Self Rating Depression Scale (SDS, Self Rating Anxiety Scale (SAS, and the Screen for Child Anxiety Related Emotional Disorders (SCARED. Peripheral blood dopamine, serotonin and norepinephrine were assayed. The mean level of norepinephrine was lower in the IAD group than that in the typically developing participants, while dopamine and serotonin levels did not differ. The SDS, SAS and SCARED symptom scores were increased in the adolescents with IAD. A logistic regression analysis revealed that a higher SAS score and lower level of norepinephrine independently predicted IAD group membership. There was no significant correlation between hours spent online and scores of SAS/SDS in IAD group. CONCLUSIONS/SIGNIFICANCE: Increased self-reported anxiety and lower peripheral blood norepinephrine are independently associated with IAD.

  8. Comparison of psychological symptoms and serum levels of neurotransmitters in Shanghai adolescents with and without internet addiction disorder: a case-control study.

    Science.gov (United States)

    Zhang, Hong-Xia; Jiang, Wen-Qing; Lin, Zhi-Guang; Du, Ya-Song; Vance, Alasdair

    2013-01-01

    Internet addiction disorder (IAD) is now recognized internationally and is known to be linked with academic and social impairment. To date, we know little about its associated main biological factors. This study aimed to collect a carefully defined group of adolescents with IAD and an age- and gender-matched typically developing comparison group. We hypothesized that the young people with IAD would have higher rates of self-reported anxiety and depressive symptoms, have altered levels of peripheral blood dopamine, norepinephrine and serotonin. In addition, we hypothesized the hours spent online are correlated with the severity of depression and anxiety among these young people with IAD. A cross-sectional study of 20 adolescents who met Beard's criteria for IAD and 15 typically developing adolescents (comparison group) was conducted. All the participants completed the Self Rating Depression Scale (SDS), Self Rating Anxiety Scale (SAS), and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Peripheral blood dopamine, serotonin and norepinephrine were assayed. The mean level of norepinephrine was lower in the IAD group than that in the typically developing participants, while dopamine and serotonin levels did not differ. The SDS, SAS and SCARED symptom scores were increased in the adolescents with IAD. A logistic regression analysis revealed that a higher SAS score and lower level of norepinephrine independently predicted IAD group membership. There was no significant correlation between hours spent online and scores of SAS/SDS in IAD group. Increased self-reported anxiety and lower peripheral blood norepinephrine are independently associated with IAD.

  9. Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

    Directory of Open Access Journals (Sweden)

    Mustafa Aydın

    2012-03-01

    Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

  10. Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus at peri-implantation.

    Science.gov (United States)

    Wu, Weiwei; Kong, Shuangbo; Wang, Bingyan; Chen, Yongjie; Wang, Haibin

    2016-02-01

    Successful implantation requires intimate interactions between a competent blastocyst and a receptive uterus. We recently demonstrated that the aberrant activation of opioid signaling by exogenous ligands adversely affects preimplantation embryonic development and subsequent implantation in mice. However, the underlying machinery governing the dynamic homeostasis of the endogenous opioid system in the uterus during early pregnancy remains elusive. We now show that all three major endogenous opioid precursors are spatiotemporally expressed in the uterus during early pregnancy. Moreover, we observe the well-coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3) at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type 1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend to reduce the uterine levels of opioid ligand precursors in the ovariectomized mouse model. This tight regulation of the endogenous opioid system by PC1/3, Pcsk1n and MME has been further confirmed in physiologically related pseudopregnancy and delayed implantation mouse models. The coordinated regulation of opioid precursor biosynthesis and metabolism helps to create appropriate opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous uterine opioid levels are primarily determined by the coordinated expressions of PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our findings raise an additional cautionary note regarding the effects of opioid abuse on early pregnancy events.

  11. Studies on the pathogenesis of fever. IX. Characteristics of endogenous serum pyrogen and mechanisms governing its release.

    Science.gov (United States)

    PETERSDORF, R G; KEENE, W R; BENNETT, I L

    1957-12-01

    The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

  12. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  13. Endogenous growth and environmental policy

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  14. Effects of disulfiram on choice behavior in a rodent gambling task: association with catecholamine levels.

    Science.gov (United States)

    Di Ciano, Patricia; Manvich, Daniel F; Pushparaj, Abhiram; Gappasov, Andrew; Hess, Ellen J; Weinshenker, David; Le Foll, Bernard

    2018-01-01

    Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in humans. The purpose of the present study was to determine whether disulfiram affects performance on a rat gambling task, a rodent version of the Iowa gambling task in humans, and whether any changes were associated with alterations in dopamine and/or norepinephrine levels. Rats were administered disulfiram prior to testing on the rat gambling task or prior to analysis of dopamine or norepinephrine levels in brain homogenates. Rats in the behavioral task were divided into two subgroups (optimal vs suboptimal) based on their baseline levels of performance in the rat gambling task. Rats in the optimal group chose the advantageous strategy more, and rats in the suboptimal group (a parallel to problem gambling) chose the disadvantageous strategy more. Rats were not divided into optimal or suboptimal groups prior to neurochemical analysis. Disulfiram administered 2 h, but not 30 min, before the task dose-dependently improved choice behavior in the rats with an initial disadvantageous "gambling-like" strategy, while having no effect on the rats employing an advantageous strategy. The behavioral effects of disulfiram were associated with increased striatal dopamine and decreased striatal norepinephrine. These findings suggest that combined actions on dopamine and norepinephrine may be a useful treatment for gambling disorders.

  15. Endogenous Sheet-Averaged Tension Within a Large Epithelial Cell Colony.

    Science.gov (United States)

    Dumbali, Sandeep P; Mei, Lanju; Qian, Shizhi; Maruthamuthu, Venkat

    2017-10-01

    Epithelial cells form quasi-two-dimensional sheets that function as contractile media to effect tissue shape changes during development and homeostasis. Endogenously generated intrasheet tension is a driver of such changes, but has predominantly been measured in the presence of directional migration. The nature of epithelial cell-generated forces transmitted over supracellular distances, in the absence of directional migration, is thus largely unclear. In this report, we consider large epithelial cell colonies which are archetypical multicell collectives with extensive cell-cell contacts but with a symmetric (circular) boundary. Using the traction force imbalance method (TFIM) (traction force microscopy combined with physical force balance), we first show that one can determine the colony-level endogenous sheet forces exerted at the midline by one half of the colony on the other half with no prior assumptions on the uniformity of the mechanical properties of the cell sheet. Importantly, we find that this colony-level sheet force exhibits large variations with orientation-the difference between the maximum and minimum sheet force is comparable to the average sheet force itself. Furthermore, the sheet force at the colony midline is largely tensile but the shear component exhibits significantly more variation with orientation. We thus show that even an unperturbed epithelial colony with a symmetric boundary shows significant directional variation in the endogenous sheet tension and shear forces that subsist at the colony level.

  16. Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels

    DEFF Research Database (Denmark)

    Domanski, Michal; Molloy, Kelly; Jiang, Hua

    2012-01-01

    An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous...

  17. A novel sensor made of Antimony Doped Tin Oxide-silica composite sol on a glassy carbon electrode modified by single-walled carbon nanotubes for detection of norepinephrine.

    Science.gov (United States)

    Wang, Zhao; Wang, Kai; Zhao, Lu; Chai, Shigan; Zhang, Jinzhi; Zhang, Xiuhua; Zou, Qichao

    2017-11-01

    In this study, we designed a novel molecularly imprinted polymer (MIP), Antimony Doped Tin Oxide (ATO)-silica composite sol, which was made using a sol-gel method. Then a sensitive and selective imprinted electrochemical sensor was constructed with the ATO-silica composite sol on a glassy carbon electrode modified by single-walled carbon nanotubes (SWNTs). The introduction of SWNTs increased the sensitivity of the MIP sensor. The surface morphology of the MIP and MIP/SWNTs were characterized by scanning electron microscopy (SEM), and the optimal conditions for detection were determined. The oxidative peak current increased linearly with the concentration of norepinephrine in the range of 9.99×10 -8 M to 1.50×10 -5 M, as detected by cyclic voltammetry (CV), the detection limit was 3.33×10 -8 M (S/N=3). In addition, the proposed electrochemical sensors were successfully applied to detect the norepinephrine concentration in human blood serum samples. The recoveries of the sensors varied from 99.67% to 104.17%, indicating that the sensor has potential for the determination of norepinephrine in clinical tests. Moreover, the imprinted electrochemical sensor was used to selectively detect norepinephrine. The analytical application was conducted successfully and yielded accurate and precise results. Copyright © 2017. Published by Elsevier B.V.

  18. A subset of osteoblasts expressing high endogenous levels of PPARgamma switches fate to adipocytes in the rat calvaria cell culture model.

    Directory of Open Access Journals (Sweden)

    Yuji Yoshiko

    2010-07-01

    Full Text Available Understanding fate choice and fate switching between the osteoblast lineage (ObL and adipocyte lineage (AdL is important to understand both the developmental inter-relationships between osteoblasts and adipocytes and the impact of changes in fate allocation between the two lineages in normal aging and certain diseases. The goal of this study was to determine when during lineage progression ObL cells are susceptible to an AdL fate switch by activation of endogenous peroxisome proliferator-activated receptor (PPARgamma.Multiple rat calvaria cells within the ObL developmental hierarchy were isolated by either fractionation on the basis of expression of alkaline phosphatase or retrospective identification of single cell-derived colonies, and treated with BRL-49653 (BRL, a synthetic ligand for PPARgamma. About 30% of the total single cell-derived colonies expressed adipogenic potential (defined cytochemically when BRL was present. Profiling of ObL and AdL markers by qRT-PCR on amplified cRNA from over 160 colonies revealed that BRL-dependent adipogenic potential correlated with endogenous PPARgamma mRNA levels. Unexpectedly, a significant subset of relatively mature ObL cells exhibited osteo-adipogenic bipotentiality. Western blotting and immunocytochemistry confirmed that ObL cells co-expressed multiple mesenchymal lineage determinants (runt-related transcription factor 2 (Runx2, PPARgamma, Sox9 and MyoD which localized in the cytoplasm initially, and only Runx2 translocated to the nucleus during ObL progression. Notably, however, some cells exhibited both PPARgamma and Runx2 nuclear labeling with concomitant upregulation of expression of their target genes with BRL treatment.We conclude that not only immature but a subset of relatively mature ObL cells characterized by relatively high levels of endogenous PPARgamma expression can be switched to the AdL. The fact that some ObL cells maintain capacity for adipogenic fate selection even at relatively

  19. Assay method and compositions

    International Nuclear Information System (INIS)

    1977-01-01

    Methods are described for measuring catecholamine levels in human and animal body fluids and tissues using the catechol-O-methyl-transferase (COMT) radioassay. The assay involves incubating the biological sample with COMT and the tritiated methyl donor, S-adenosyl-L-methionine( 3 H)-methyl. The O-methylated ( 3 H) epinephrine and/or norepinephrine are extracted and oxidised to vanillin- 3 H which in turn is extracted and its radioactivity counted. When analysing dopamine levels the assay is extended by vanillin- 3 H and raising the pH of the aqueous periodate phase from which O-methylated ( 3 H) dopamine is extracted and counted. The assay may be modified depending on whether measurements of undifferentiated total endogenous catecholamine levels or differential analyses of the catecholamine levels are being performed. The sensitivity of the assay can be as low as 5 picograms for norepinephrine and epinephrine and 12 picograms for dopamine. The assemblance of the essential components of the assay into a kit for use in laboratories is also described. (U.K.)

  20. Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Somogyi, G.T.; de Groat, W.C. (Univ. of Pittsburgh, PA (USA))

    1990-10-01

    Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activation of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.

  1. Endogenous pyrogen-like substance produced by reptiles.

    Science.gov (United States)

    Bernheim, H A; Kluger, M J

    1977-06-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

  2. Influence of chronic captopril treatment on norepinephrine-induced vasoconstriction in SHR and WKY : In vivo study

    Czech Academy of Sciences Publication Activity Database

    Pintérová, Mária; Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2008-01-01

    Roč. 26, Suppl.1 (2008), S174-S174 ISSN 0263-6352. [Scientific Meeting International Society of Hypertension /22./ , Scientific Meeting European Society of Hypertension /18./. 14.06.2008-19.06.2008, Berlin] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * captopril teratment * norepinephrine-induced vasoconstriction * SHR and WKY Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  3. The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets

    DEFF Research Database (Denmark)

    Mikkelsen, Mai Louise Grandsgaard; Ambrus, Rikard; Rasmussen, Rune

    2018-01-01

    of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation). Results During propofol......–remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0......–remifentanil–dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group. Conclusions Cerebral partial pressure of oxygen measured by Licox...

  4. Endogenous leukotriene formation during anaphylactic shock

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

  5. A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

    Science.gov (United States)

    Zhu, Xiaoyan; Fréchou, Magalie; Liere, Philippe; Zhang, Shaodong; Pianos, Antoine; Fernandez, Neïké; Denier, Christian; Mattern, Claudia; Schumacher, Michael; Guennoun, Rachida

    2017-11-08

    Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the

  6. Antidiabetic and Plasma Endogenous Antioxidant Activity of alstonia ...

    African Journals Online (AJOL)

    Alstonia boonei is a well-known plant of medicinal value but its effect on endogenous plasma antioxidant in diabetes remains unknown. Thus, need to investigate the effects of the methanolic extract of the plant on plasma bilirubin and uric acid level in alloxan induced diabetes rabbits. Twenty five rabbits divided into five ...

  7. Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Peredo, H; Agostini, M D; Gimeno, M F; Borda, E S

    1984-08-01

    Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-/sup 14/C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.

  8. Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.

    Science.gov (United States)

    Jung, Younghun; Decker, Ann M; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A; Yumoto, Kenji; Cackowski, Frank C; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M; Taichman, Russell S

    2016-05-03

    GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.

  9. Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

    Science.gov (United States)

    Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

    2015-05-01

    Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

  10. Differential RISC association of endogenous human microRNAs predicts their inhibitory potential.

    Science.gov (United States)

    Flores, Omar; Kennedy, Edward M; Skalsky, Rebecca L; Cullen, Bryan R

    2014-04-01

    It has previously been assumed that the generally high stability of microRNAs (miRNAs) reflects their tight association with Argonaute (Ago) proteins, essential components of the RNA-induced silencing complex (RISC). However, recent data have suggested that the majority of mature miRNAs are not, in fact, Ago associated. Here, we demonstrate that endogenous human miRNAs vary widely, by >100-fold, in their level of RISC association and show that the level of Ago binding is a better indicator of inhibitory potential than is the total level of miRNA expression. While miRNAs of closely similar sequence showed comparable levels of RISC association in the same cell line, these varied between different cell types. Moreover, the level of RISC association could be modulated by overexpression of complementary target mRNAs. Together, these data indicate that the level of RISC association of a given endogenous miRNA is regulated by the available RNA targetome and predicts miRNA function.

  11. Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.

    Science.gov (United States)

    Xue, Yan-Feng; Zhang, Meng; Qi, Zhong-Qiang; Li, You-Qin; Shi, Zhiqi; Chen, Jian

    2016-02-01

    Cinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism. The lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA-induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation. CA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching. © 2015 Society of Chemical Industry.

  12. Role of endogenous opioid peptides in the pathogenesis of motion sickness

    International Nuclear Information System (INIS)

    Yasnetsov, V.V.; Il'ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

    1986-01-01

    This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness

  13. Role of endogenous opioid peptides in the pathogenesis of motion sickness

    Energy Technology Data Exchange (ETDEWEB)

    Yasnetsov, V.V.; Il' ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

    1986-01-01

    This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness.

  14. Effect of CPPU on Carbohydrate and Endogenous Hormone Levels in Young Macadamia Fruit.

    Directory of Open Access Journals (Sweden)

    Hui Zeng

    Full Text Available N-(2-Chloro-4-pyridyl-N'-phenylurea (CPPU is a highly active cytokinin-like plant growth regulator that promotes chlorophyll biosynthesis, cell division, and cell expansion. It also increases fruit set and accelerates fruit enlargement. However, there has been no report about the effect of CPPU on fruit development and its physiological mechanism in macadamia. In this study, we investigated the effect of CPPU treatment at early fruit development via foliar spray or raceme soaking at 20 mg·L-1 on fruit set and related physiology in macadamia. Changes in carbohydrate contents and endogenous hormones in leaves, bearing shoots and fruit were also examined. Results showed that CPPU significantly reduced young fruit drop and delayed the wave of fruit drop by 1-2 weeks. The treatment significantly decreased the contents of total soluble sugars and starch in the leaves, but increased them in the bearing shoots and total soluble sugars in the husk (pericarp and seeds. These findings suggested that CPPU promoted carbohydrate mobilization from the leaves to the fruit. In addition, CPPU increased the contents of indole-3-acetic acid (IAA, gibberellin acid (GA3, and zeatin riboside (ZR and decreased the abscisic acid (ABA in the husk. Therefore, CPPU treatment reduced the early fruit drop by increasing carbohydrate availability and by modifying the balance among endogenous hormones.

  15. The interactions of multisensory integration with endogenous and exogenous attention

    Science.gov (United States)

    Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

    2016-01-01

    Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

  16. Neutral endopeptidase 24.11 is important for the degradation of both endogenous and exogenous glucagon in anesthetized pigs

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Klarskov, Letty; Olesen, Mette

    2004-01-01

    , a selective NEP inhibitor, on plasma levels of endogenous and exogenous glucagon was examined in anesthetized pigs. Candoxatril increased endogenous glucagon concentrations, from 6.3 +/- 2.5 to 20.7 +/- 6.3 pmol/l [COOH-terminal (C)-RIA, P ...-RIA). This study provides evidence that NEP 24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo....

  17. Endogenous egg immune defenses in the yellow mealworm beetle (Tenebrio molitor).

    Science.gov (United States)

    Jacobs, Chris G C; Gallagher, Joe D; Evison, Sophie E F; Heckel, David G; Vilcinskas, Andreas; Vogel, Heiko

    2017-05-01

    In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Clinical study of the hypothesis of endogenous collateral wind on acute coronary syndrome: a review.

    Science.gov (United States)

    Wang, Xian; Zhang, Cong; Yang, Ran; Zhu, Haiyan; Zhao, Huaibing; Li, Xiaoming

    2014-01-01

    Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of "endogenous collateral wind" based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine. Through successful coronary angiography (CAG), and intravascular ultrasound (IVUS), patients with coronary artery disease were made the differential diagnosis such as blood stasis, blood stasis due to phlegm obstruction, and endogenous collateral wind. The levels of plasma inflammatory marker were measured to study on the characteristics of "endogenous collateral wind". Luo heng dripping pills with promoting blood circulation to expel wind-evil, and remove wetness were made based on the hypothesis of "endogenous collateral wind" on ACS. Patients with unstable angina were randomly divided into 3, groups based on therapeutic methods: conventional therapy group, Luo Heng dripping pills group and Tongxinluo caps. Differences among groups were compared. There were great changes in number and degree of coronary arteriostenosis confirmed by CAG, the types of ACC/AHA lesion and Levin lesion confirmed by CAG, remodeling index, positive or negative remodeling percentage measured by IVUS, the plasma levels of plasma inflammatory marker measured by ELLSA in the patients with endogenous collateral wind, compared with patients with blood stasis and blood stasis due to phlegm obstruction. The total effective rate of improved angina in Luo Heng dripping pills group was significantly higher than those in other two groups. The levels of plasma inflammatory marker were significantly lower in Luo Heng dripping pills group. There were some pathological basis which were found about the hypothesis of "endogenous collateral wind" on acute coronary syndrome. It provided evidences for patients with coronary artery disease treated by medicines with

  19. [Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

    Science.gov (United States)

    Fan, Xin-rong; Tang, Nong; Ji, Yun-xi; Zhang, Yao-zhong; Jiang, Li; Huang, Gui-hua; Xie, Sheng; Li, Liu-mei; Song, Chun-hui; Ling, Jiang-hong

    2015-08-01

    The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.

  20. Noise stimulation decreases the concentration of norepinephrine in the rat cochlea.

    Science.gov (United States)

    Vicente-Torres, M A; Gil-Loyzaga, P

    1999-05-14

    The present study was designed to analyze, by using high performance liquid chromatography (HPLC), the effect of acoustic stimulation on the cochlear concentration of norepinephrine (NE). Independently of the rat strain (Long-Evans or Wistar strains), NE concentration decreased about 18% when animals were exposed to white noise (90 dB SPL for 1 h). The same decrease was observed in animals perfused by aortic pathway to remove the blood, indicating that this decrease corresponds exclusively to a neurophysiological process. In fact, these findings could indicate that noise stimulation is involved in the NE release from sympathetic fibers innervating the cochlea. This likely release of NE supports that sympathetic fibers play a functional role in cochleae exposed to noisy situations.

  1. Probing Endogenous Collagen by Laser Induced Autofluorescence in Burn Wound Biopsies- A Pilot Study.

    Science.gov (United States)

    Prabhu, Vijendra; Acharya, Anusha; Rao, Bola Sadashiva Satish; Rathnakar, Bharath; Kumar, Pramod; Guddattu, Vasudeva; Mahato, Krishna Kishore

    2018-04-19

    The focus of the current study was to interrogate the predictive potential of laser-induced autofluorescence (LIAF) by objectively assessing collagen synthesis in burn wound granulation tissues ex vivo. Prior grafting, granulation tissues (20 samples) following burn injury were collected from 17 subjects of age range 18- 60 years with patient/donor consent and the corresponding autofluorescence spectra were recorded at 325 nm He-Cd laser (≈ 2 mW) excitations. The resulting endogenous collagen intensity from the above tissue samples was computed by normalizing the NADH levels. In addition, the hydroxyproline content was also estimated biochemically from the same granulation tissues. A comparative assessment of both LIAF and biochemical estimations for endogenous collagen by hydroxyproline resulted in strong positive correlation among them. The above relevant observations suggest that LIAF is equally informative as that of biochemical estimations, in evaluating endogenous collagen content in wound granulation tissues. Thus, it can be concluded that LIAF has the predictive potential, as a non-invasive objective tool to measure the endogenous collagen levels in wound biopsy tissues and provide complementary data conducive for making clinical decisions. This article is protected by copyright. All rights reserved.

  2. Estimation of the endogenous N proportions in ileal digesta and faeces in 15N-labelled pigs

    International Nuclear Information System (INIS)

    Simon, O.; Bergner, H.

    1987-01-01

    4 castrated male pigs 40 kg fitted with simple 'T' cannulas in the terminal ileum were given 15 N-labelled ammonium salts, added to a low protein diet, for 6 days. Excretion of 15 N in urine and feces was monitored daily throughout the labelling and subsequent experimental periods. During the experimental period the pigs were given a diet based on wheat and fish meal, supplemented with varying levels of partially hydrolyzed straw meal to give crude fiber contents ranging from 40 to 132 g/kg. After adaptation to the particular levels of straw meal, feces and ileal digesta were collected during successive 24 h periods. N digestibility values were determined by the chromium oxide ratio method. The retention of 15 N-labelled non-specific N was 0.46 of the dose given. The validity of using urine values as a measure of 15 N abundance in endogenous N was demonstrated by the similarity of 15 N abundance in urine immediately before slaughter at the end of the experiment and in the digestive secretory organs thereafter. The average amount of endogenous N passing the terminal ileum was 3.4 g/day or 0.30-0.50 of total ileal N flow. This was not affected by dietary fiber level. The proportion of fecal N which was of endogenous origin was similar to that in ileal digesta, suggesting similar utilization of endogenous and residual dietary N by hindgut bacteria. Half the endogenous N entering the large intestine was reabsorbed there. Increasing dietary crude fiber from 40 to 132 g/kg increased fecal endogenous N excretion from 1.3 to 2.0 g/animal and day. (author)

  3. Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.

    Science.gov (United States)

    Ansorge, Mark S; Morelli, Emanuela; Gingrich, Jay A

    2008-01-02

    Serotonin (5-HT) acts as a neurotransmitter, but also modulates brain maturation during early development. The demonstrated influence of genetic variants on brain function, personality traits, and susceptibility to neuropsychiatric disorders suggests a critical importance of developmental mechanisms. However, little is known about how and when developmentally perturbed 5-HT signaling affects circuitry and resulting behavior. The 5-HT transporter (5-HTT) is a key regulator of extracellular 5-HT levels and we used pharmacologic strategies to manipulate 5-HTT function during development and determine behavioral consequences. Transient exposure to the 5-HTT inhibitors fluoxetine, clomipramine, and citalopram from postnatal day 4 (P4) to P21 produced abnormal emotional behaviors in adult mice. Similar treatment with the norepinephrine transporter (NET) inhibitor, desipramine, did not adversely affect adult behavior, suggesting that 5-HT and norepinephrine (NE) do not share the same effects on brain development. Shifting our period of treatment/testing to P90/P185 failed to mimic the effect of earlier exposure, demonstrating that 5-HT effects on adult behavior are developmentally specific. We have hypothesized that early-life perturbations of 5-HT signaling affect corticolimbic circuits that do not reach maturity until the peri-adolescent period. In support of this idea, we found that abnormal behaviors resulting from postnatal fluoxetine exposure have a post-pubescent onset and persist long after reaching adult age. A better understanding of the underlying 5-HT sensitive circuits and how they are perturbed should lead to new insights into how various genetic polymorphisms confer their risk to carriers. Furthermore, these studies should help determine whether in utero exposure to 5-HTT blocking drugs poses a risk for behavioral abnormalities in later life.

  4. Ciliary neurotrophic factor is an endogenous pyrogen.

    Science.gov (United States)

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-09-15

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  5. Biology and evolution of the endogenous koala retrovirus.

    Science.gov (United States)

    Tarlinton, R; Meers, J; Young, P

    2008-11-01

    Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).

  6. Development, Validation, and Interlaboratory Evaluation of a Quantitative Multiplexing Method To Assess Levels of Ten Endogenous Allergens in Soybean Seed and Its Application to Field Trials Spanning Three Growing Seasons.

    Science.gov (United States)

    Hill, Ryan C; Oman, Trent J; Wang, Xiujuan; Shan, Guomin; Schafer, Barry; Herman, Rod A; Tobias, Rowel; Shippar, Jeff; Malayappan, Bhaskar; Sheng, Li; Xu, Austin; Bradshaw, Jason

    2017-07-12

    As part of the regulatory approval process in Europe, comparison of endogenous soybean allergen levels between genetically engineered (GE) and non-GE plants has been requested. A quantitative multiplex analytical method using tandem mass spectrometry was developed and validated to measure 10 potential soybean allergens from soybean seed. The analytical method was implemented at six laboratories to demonstrate the robustness of the method and further applied to three soybean field studies across multiple growing seasons (including 21 non-GE soybean varieties) to assess the natural variation of allergen levels. The results show environmental factors contribute more than genetic factors to the large variation in allergen abundance (2- to 50-fold between environmental replicates) as well as a large contribution of Gly m 5 and Gly m 6 to the total allergen profile, calling into question the scientific rational for measurement of endogenous allergen levels between GE and non-GE varieties in the safety assessment.

  7. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  8. In vivo assessment of [11C]MRB as a prospective PET ligand for imaging the norepinephrine transporter

    International Nuclear Information System (INIS)

    Severance, Alin J.; Milak, Matthew S.; Dileep Kumar, J.S.; Arango, Victoria; Parsey, Ramin V.; Prabhakaran, Jaya; Majo, Vattoly J.; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J.J.

    2007-01-01

    Antagonism of norepinephrine reuptake is now an important pharmacological strategy in the treatment of anxiety and depressive disorders, and many antidepressants have substantial potential occupancy of the norepinephrine transporter (NET) at recommended dosages. Despite the importance of understanding this transporter's role in psychiatric disease and treatment, a suitable radioligand for studying NET has been slow to emerge. (S,S)-Methylreboxetine (MRB) is among the more promising ligands recently adapted for positron emission tomography (PET), and the present study aimed to evaluate its potential for use in higher primates. Affinities for various brain targets were determined in vitro. PET studies were conducted in baboon under both test-retest and blocking conditions using 1 mg/kg nisoxetine. MRB has sixfold higher affinity for NET than the serotonin transporter, and negligible affinity for other sites. PET studies in baboons showed little regional heterogeneity in binding and were minimally affected by pretreatment with the NET antagonist nisoxetine. Despite improvement over previous ligands for imaging NET in vivo, the low signal to noise ratio indicates [ 11 C]MRB lacks sensitivity and reliability as a PET radiotracer in humans. (orig.)

  9. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  10. Features of Cytokine Regulation in Multidrug-Resistant Tuberculosis Depending on Severity of Endogenous Intoxication

    Directory of Open Access Journals (Sweden)

    L.D. Todoriko

    2016-02-01

    Conclusions. Comprehensive assessment of integral indices of endogenous intoxication and level of certain pro- and anti-inflammatory cytokines in the blood plasma of patients with MDR TB shows a moderate endogenous intoxication, break down of the cellular component of the immune reactivity due to the formation of conditions for the development of Mycobacterium tuberculosis resistance, with further growth of cytotoxic hypoxia and activation of systemic inflammatory response syndrome. Analysis of plasma concentration of IL-6, IL-10 and IL-18 in patients with multidrug-resistance proved, that their level depends on the nature of Mycobacterium tuberculosis resistance.

  11. Effect of cotyledons and epicotyl upon the activity of endogenous gibberellins in roots of flax (Linum usitatissimum L. seedlings

    Directory of Open Access Journals (Sweden)

    Krystyna M. Janas

    2013-12-01

    Full Text Available In 11-day-old flax seedlings, the level of endogenous gibberellins in roots decreased within 12 hours after the excision of cotyledons and the epicotyl; however, 24 to 48 hours after excision the gibberellin level increased again. The decrease in the gibberellin level within the first 12 hours after excision suggests a participation of the cotyledons and the epicotyl in the biosynthesis of endogenous gibberellins.

  12. An efficient probe for rapid detection of cyanide in water at parts per billion levels and naked-eye detection of endogenous cyanide.

    Science.gov (United States)

    Kumari, Namita; Jha, Satadru; Bhattacharya, Santanu

    2014-03-01

    A new molecular probe based on an oxidized bis-indolyl skeleton has been developed for rapid and sensitive visual detection of cyanide ions in water and also for the detection of endogenously bound cyanide. The probe allows the "naked-eye" detection of cyanide ions in water with a visual color change from red to yellow (Δλmax =80 nm) with the immediate addition of the probe. It shows high selectivity towards the cyanide ion without any interference from other anions. The detection of cyanide by the probe is ratiometric, thus making the detection quantitative. A Michael-type addition reaction of the probe with the cyanide ion takes place during this chemodosimetric process. In water, the detection limit was found to be at the parts per million level, which improved drastically when a neutral micellar medium was employed, and it showed a parts-per-billion-level detection, which is even 25-fold lower than the permitted limits of cyanide in water. The probe could also efficiently detect the endogenously bound cyanide in cassava (a staple food) with a clear visual color change without requiring any sample pretreatment and/or any special reaction conditions such as pH or temperature. Thus the probe could serve as a practical naked-eye probe for "in-field" experiments without requiring any sophisticated instruments. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Interaction between endogenous and exogenous orienting in crossmodal attention.

    Science.gov (United States)

    Chen, Xiaoxi; Chen, Qi; Gao, Dingguo; Yue, Zhenzhu

    2012-08-01

    Using a cue-target paradigm, we investigated the interaction between endogenous and exogenous orienting in cross-modal attention. A peripheral (exogenous) cue was presented after a central (endogenous) cue with a variable time interval. The endogenous and exogenous cues were presented in one sensory modality (auditory in Experiment 1 and visual in Experiment 2) whereas the target was presented in another modality. Both experiments showed a significant endogenous cuing effect (longer reaction times in the invalid condition than in the valid condition). However, exogenous cuing produced a facilitatory effect in both experiments in response to the target when endogenous cuing was valid, but it elicited a facilitatory effect in Experiment 1 and an inhibitory effect in Experiment 2 when endogenous cuing was invalid. These findings indicate that endogenous and exogenous cuing can co-operate in orienting attention to the crossmodal target. Moreover, the interaction between endogenous and exogenous orienting of attention is modulated by the modality between the cue and the target. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  14. Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.

    Science.gov (United States)

    Zhang, Yan; Yang, Jun; Wang, Tao; Wang, Shao-Gang; Liu, Ji-Hong; Yin, Chun-Ping; Ye, Zhang-Qun

    2016-03-01

    Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats. Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition. Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs. Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S-generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group. Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE

  15. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  16. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

    Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

  17. The interactions of multisensory integration with endogenous and exogenous attention.

    Science.gov (United States)

    Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

    2016-02-01

    Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

    International Nuclear Information System (INIS)

    Knepper, S.M.

    1985-01-01

    Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with 3 H-myo-inositol and 3 H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of 3 H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10 -7 M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level. Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo[2.2.1]heptene, and endo and exo conformers of 2-aminobenzobicyclo[2.2.1]heptene and 2-aminobenzobicyclo[2.2.2]octene

  19. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  20. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Therese Wilhelm

    2016-05-01

    Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

  1. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Science.gov (United States)

    Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

    2016-05-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  2. α-Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation.

    Science.gov (United States)

    Moon, Jae Yun; Choi, Su Jin; Heo, Cheol Ho; Kim, Hwan Myung; Kim, Hye Sun

    2017-07-01

    α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis. Two-photon microscopy imaging showed that excessive intracellular ROS accumulated during the differentiation of SNKD cells as compared with control cells. The formation of 4-hydroxynonenal adduct, a byproduct of lipid peroxidation during oxidative stress, significantly increased in differentiated SNKD myotubes and was dramatically reduced by epigallocatechin-3-gallate, a well-known ROS scavenger. Among antioxidant enzymes, catalase was significantly decreased during differentiation of SNKD cells without changes at the mRNA level. Of interest was the finding that the degradation of catalase was rescued by MG132, a proteasome inhibitor, in the SNKD cells. This study demonstrates a novel function of α-syntrophin. This protein plays an important role in the regulation of oxidative stress from endogenously generated ROS during myoblast differentiation by modulating the protein stability of catalase. © 2017 Federation of European Biochemical Societies.

  3. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  4. Radioenzymatic test for catecholamines

    International Nuclear Information System (INIS)

    Johnson, G.A.; Peuler, J.D.

    1977-01-01

    The invention deals with a method to determine total endogenic epinephrine and norepinephrine in human and mammal systems consisting of a supernatant of deproteinated tissue homogenate, blood serum, or blood plasma. The method uses a tritium tracer technique where the epinephrine (norepinephrine) is reactet to O-methylated ( 3 H) epinephrine (norepinephrine) in an enzymatic reaction while the product is oxygenated to vanillin- 3 H and analyzed with the aid of a liquid scintillation spectrometer. Another patent claim deals with a method for the purification of the enzyme catechin-O-methyl transferase from rat liver and ways to optimize the enzymatic reaction as well as with a method of optimizing oxygenation to vanillin- 3 H, its isolation and measurements. (VJ) [de

  5. Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens.

    Science.gov (United States)

    Basu, Subhasree; Rajakaruna, Suren; Dickinson, Bryan C; Chang, Christopher J; Menko, A Sue

    2014-01-01

    Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens. Embryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy. PF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an

  6. Activation of endogenous opioid gene expression in human keratinocytes and fibroblasts by pulsed radiofrequency energy fields

    Directory of Open Access Journals (Sweden)

    Moffett J

    2012-09-01

    Full Text Available John Moffett,1 Linley M Fray,1 Nicole J Kubat21Life Science Department, 2Independent Consultant, Regenesis Biomedical Inc, Scottsdale, AZ, USABackground: Pulsed radiofrequency energy (PRFE fields are being used increasingly for the treatment of pain arising from dermal trauma. However, despite their increased use, little is known about the biological and molecular mechanism(s responsible for PRFE-mediated analgesia. In general, current therapeutics used for analgesia target either endogenous factors involved in inflammation, or act on endogenous opioid pathways.Methods and Results: Using cultured human dermal fibroblasts (HDF and human epidermal keratinocytes (HEK, we investigated the effect of PRFE treatment on factors, which are involved in modulating peripheral analgesia in vivo. We found that PRFE treatment did not inhibit cyclooxygenase enzyme activity, but instead had a positive effect on levels of endogenous opioid precursor mRNA (proenkephalin, pro-opiomelanocortin, prodynorphin and corresponding opioid peptide. In HEK cells, increases in opioid mRNA were dependent, at least in part, on endothelin-1. In HDF cells, additional pathways also appear to be involved. PRFE treatment was also followed by changes in endogenous expression of several cytokines, including increased levels of interleukin-10 mRNA and decreased levels of interleukin-1β mRNA in both cell types.Conclusion: These findings provide a new insight into the molecular mechanism underlying PRFE-mediated analgesia reported in the clinical setting.Keywords: peripheral analgesia, endogenous opioids, endothelin-1, endothelin receptor A, endothelin receptor B, pulsed radiofrequency energy field, cyclooxygenase

  7. Angiotensin receptors and norepinephrine neuromodulation: implications of functional coupling.

    Science.gov (United States)

    Gelband, C H; Sumners, C; Lu, D; Raizada, M K

    1998-02-27

    The objective of this review is to examine the role of neuronal angiotensin II (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have been identified in cardiovascularly relevant areas of the brain: the AT1 and the AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1 and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE) neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor-mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and ultimately leads to an increase in NE transporter, tyrosine hydroxylase and dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+ channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors will be discussed.

  8. Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yu-Ting Liao

    Full Text Available Enterovirus 71 (EV71 infections may be associated with neurological complications, including brainstem encephalitis (BE. Severe EV71 BE may be complicated with autonomic nervous system (ANS dysregulation and/or pulmonary edema (PE. ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.The aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines.Plasma levels of norepinephrine (NE and epinephrine (EP in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP.The plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE.The plasma levels of NE and EP elevated in EV71-infected patients with ANS

  9. Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71.

    Science.gov (United States)

    Liao, Yu-Ting; Wang, Shih-Min; Wang, Jen-Ren; Yu, Chun-Keung; Liu, Ching-Chuan

    2015-01-01

    Enterovirus 71 (EV71) infections may be associated with neurological complications, including brainstem encephalitis (BE). Severe EV71 BE may be complicated with autonomic nervous system (ANS) dysregulation and/or pulmonary edema (PE). ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release. The aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines. Plasma levels of norepinephrine (NE) and epinephrine (EP) in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs) on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs) were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP. The plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE. The plasma levels of NE and EP elevated in EV71-infected patients with ANS dysregulation and

  10. Endogenous hormones in postmenopausal females with breast cancer--before and after treatment.

    Science.gov (United States)

    Trehan, Aniljeet S; Arora, Megha K; Seth, Shashi; Chauhan, Ashok

    2012-01-01

    Breast cancer is usually present for many years (as long as 5-10 years) before it can be clinically diagnosed (theory of the 'dormant malignant cell'). This implies that breast cancer cells, during their subclinical period, are likely to have been exposed for a considerable time to endogenous sex hormones and endogenous hormonal milieu predicts the chances of breast cancer in females. So, we planned this study to evaluate the role of endogenous hormones in postmenopausal females excluding the patients on hormone replacement therapy as the relationship between breast cancer and hormone replacement therapy is well known. Hormone therapy is known to affect these hormone levels but whether treatment of breast cancer per se also decreases the hormone levels is not known. We planned the present study to determine hormone levels in patients before and after 4 months of treatment (chemotherapy/surgery and radiotherapy). Circulating hormone levels were measured using a chemiluminescence method. Their results were compared with a group of 25 age matched healthy controls. We found that serum prolactin, testosterone and estrogen levels were very significantly higher in patients before treatment (Group I) as compared to controls (Group III). Serum prolactin and serum estrogen levels were significantly higher and serum testosterone was very significantly higher in patients before treatment (Group I) when compared after 4 months of treatment (Group II). Only serum estrogen levels were significantly high in patients after treatment (Group II) as compared to controls (Group III). Serum progesterone levels showed no significant difference to any of the groups. We concluded that postmenopausal females with breast cancer have abnormalities in hormone levels. These abnormalities may be considered in the pathogenesis of the disease and should be taken into account in the treatment of patients of breast cancer. It might also be helpful to delay the onset of cancer by normalizing the

  11. Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

    Science.gov (United States)

    Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

    2017-07-07

    Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammer, Daniel; Erichsen, Lars

    2016-01-01

    : Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...... increased with body weight in accordance with an allometrically scaled power exponent of 0.75 and 1, respectively. Endogenous FSH levels were lower in individuals with higher progesterone levels at baseline and were further suppressed over time with increasing inhibin B levels. Conclusions......: This characterisation of FE 999049 population pharmacokinetics after repeated dosing is in line with previous findings after single-dose administration. The results provide a basis for study design and data evaluation in the future development of recombinant FSH products, and show it can be of importance to account...

  13. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

    The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

  14. The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

    DEFF Research Database (Denmark)

    Biondi, Bernadette; Bartalena, Luigi; Cooper, David S

    2015-01-01

    Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective...

  15. Regulation of serotonin release from enterochromaffin cells of rat cecum mucosa

    International Nuclear Information System (INIS)

    Simon, C.; Ternaux, J.P.

    1990-01-01

    The release of endogenous serotonin or previously taken up tritiated serotonin from isolated strips of rat cecum mucosa containing enterochromaffin cells was studied in vitro. Release of tritiated serotonin was increased by potassium depolarization and was decreased by tetrodotoxin, veratridine and the absence of calcium. Endogenous serotonin was released at a lower rate than tritiated serotonin; endogenous serotonin release was stimulated by potassium depolarization but was unaffected by tetrodotoxin, veratridine or the absence of calcium. Carbachol, norepinephrine, clonidine and isoproterenol decreased release of tritiated serotonin but had less or reverse effect on release of endogenous serotonin. The results suggest two different serotoninergic pools within the enterochromaffin cell population

  16. Endogeneity and Specialization in the European Monetary Union

    Directory of Open Access Journals (Sweden)

    Bąk Henryk

    2015-06-01

    Full Text Available There has been a broad discussion about the viability of the European Monetary Union (EMU in its present and prospective confines. Generally, the EMU, consisting of 19 countries, is not considered an optimal currency area due to low labor market flexibility, autonomous fiscal policies, and structural differences among its members. Considerations about the endogeneity effect of currency unions lead to the question whether the EMU will become more viable over time. According to the endogenity hypothesis formulated by Frankel and Rose [1996, 2000], a common currency area may gradually become an optimal currency area at some future point (ex post unification, despite not having been an optimal currency area (OCA prior to (ex ante currency unification. Currency unification should bring about increased intra-industry trade and greater business cycle synchronization among member states. The most recent literature and analyses presented in this paper suggest that the endogenity effect in the EMU has been frail since its onset. While real convergence between EMU member states has not advanced, divergence in i.a. economic structures, national income and productivity levels is observed. The most important economic mechanisms reinforcing convergence and divergence among monetary union members are presented in this paper. Using recent data and related research results, we show a significant divergence in economic structures, business cycle synchronization and productivity levels among Eurozone members in the last decade. The Krugman sectorial dissimilarity index is applied to measure changes in industrial similarity among member countries and the Hodrick-Prescott filter to estimate business cycle synchronization in the EMU. These divergence tendencies have been strengthened by the global financial crisis of 2008 and persist, calling for reforms and new policies within the EMU.

  17. Be quick about it. Endogenous estradiol level, menstrual cycle phase and trait impulsiveness predict impulsive choice in the context of reward acquisition.

    Science.gov (United States)

    Diekhof, Esther K

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". Variations in the steroid hormone 17ß-estradiol (E2) may promote intra-individual differences in reward seeking behavior and temporal decision-making (Reimers et al., 2014; Front. Neurosci. 8: 401). Yet, in humans the exact role of E2 in impulsive choice still needs to be determined. The present study assessed the effect of a cycle-dependent rise in endogenous E2 on temporal response adaptation across the follicular phase (FP). For this purpose a reward acquisition paradigm was employed that is sensitive to hormone-induced changes in central dopamine (DA) level. The present data show that women acted more impulsively in the early as opposed to the late FP. Early follicular E2 further correlated with an increased capacity to speed up for reward maximization, while simultaneously the ability to wait for higher reward was compromised. This correlation was most pronounced in women with low trait impulsiveness. In contrast, E2 and optimized response speed failed to correlate in women with high trait impulsiveness and in the late FP, despite a generally higher E2 level. Collectively, these findings support the theory that E2 may act as an endogenous DA agonist. The fact that the hormone-behavior relationship was restricted to women with low trait impulsiveness and thus supposedly lower central DA level provides indirect support for this idea. Yet, choices became relatively less impulsive in the state of heightened E2 (i.e., in the late FP), suggesting that the relationship between E2 and impulsive choice may not be linear, but might resemble an inverted U-function. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  19. Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

    Science.gov (United States)

    Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

    2016-01-01

    Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

  20. The role of dopamine and norepinephrine in depression and antidepressant treatment.

    Science.gov (United States)

    Nutt, David J

    2006-01-01

    Most antidepressants in use today are descendants of the monoamine oxidase inhibitor iproniazid and the tricyclic agent imipramine. These agents were both originally developed for other indications but then were serendipitously determined to have antidepressant effects. Elucidation of the mechanisms of action of these first antidepressants, along with those of reserpine and amphetamine, led to the monoamine theories of depression. Through the past several decades, approaches undertaken to clarify the roles of the neurotransmitters norepinephrine, dopamine, and serotonin in depression have included animal studies, human biological and postmortem studies, inferences drawn from antidepressant drug actions, and challenge or depletion studies; most recently, brain imaging studies have proved to be especially informative. This research has identified novel potential targets, with the goal of developing new antidepressant drugs with better efficacy and faster onset of action than current "gold-standard" treatments.

  1. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

    Directory of Open Access Journals (Sweden)

    Samantha J. Hindle

    2017-10-01

    Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

  2. Influence of calcium-dependent potassium channel blockade and nitric oxide inhibition on norepinephrine-induced contractions in two forms of genetic hypertension

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Petrová, M.; Karen, Petr; Kuneš, Jaroslav; Zicha, Josef

    2010-01-01

    Roč. 4, č. 3 (2010), s. 128-134 ISSN 1933-1711 R&D Projects: GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : potassium channels * nitric oxide * norepinephrine Subject RIV: ED - Physiology Impact factor: 0.931, year: 2010

  3. The time-course relationship between endogenous spleen colony formation and marrow cellularity after midlethal irradiation of mice

    International Nuclear Information System (INIS)

    Koch, I.; Wiktor-Jedrzejczak, W.; Wojskowa Akademia Medyczna, Warsaw

    1981-01-01

    The kinetics of appearance and disappearance of endogenous spleen colonies following 4 and 6 Gy of X-irradiation was compared with the kinetics of changes of cellular contents of femur cavities. Additionally, the effect of postirradiation bleeding and this way of the subsequent increase in the level of endogenous erythropoietin was studied. It was found that the kinetics of endogenous haemopoietic recovery in the marrow follows the same characteristic biphasic pattern as in the spleen although it is slightly delayed in time. First wave of regeneration corresponded in time with the formation of transient endogenous spleen colonies 4-7 days postirradiation, and the 2nd wave corresponded in time witn the formation of classical haemopoietic stem-cell derived endogenous spleen colonies 9-12 days following irradiation. Postirradiation bleeding markedly stimulated particularly the first wave of regeneration both in the marrow and in the spleen. (orig.) [de

  4. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Andersen, Jacob; Kristensen, Anders Skov; Bang-Andersen, Benny

    2009-01-01

    The biogenic monoamine transporters are integral membrane proteins that perform active transport of extracellular dopamine, serotonin and norepinephrine into cells. These transporters are targets for therapeutic agents such as antidepressants, as well as addictive substances such as cocaine...... and amphetamine. Seminal advances in the understanding of the structure and function of this transporter family have recently been accomplished by structural studies of a bacterial transporter, as well as medicinal chemistry and pharmacological studies of mammalian transporters. This feature article focuses...

  5. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 59 eyes with endogenous endophthalmitis

    DEFF Research Database (Denmark)

    Bjerrum, Søren Solborg; la Cour, Morten

    2017-01-01

    BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28 to......, the visual outcome and the mortality of the patients. The epidemiology of the disease is very different in Scandinavia compared to Asia. The visual prognosis remains grave and the majority of the eyes lose useful vision....

  7. On the role of endogenous serotin in the radioprotective action of some aminothiols

    International Nuclear Information System (INIS)

    Sverdlov, A.G.; Pavlova, L.M.

    1977-01-01

    It has been studied whether there is a correlation of the radioprotective effect of cystamine (50 and 150 mg/kg by base) and its analogue, N',N'-tetramethyl cystamine (130 mg/kg by base), with the ability of these compounds to rise the endogenous serotonin content of radiosensitive organs 20 and 60 minutes after intraperitoneal administration to mice. The ability of sulphur-containing radioprotectors does not necessarily correlate with their preventive properties: an ineffective radioprotector analogue, N',N'-tetramethyl cystamine, has the same effect on the endogeneous serotonin level as the protector itself

  8. Independent effects of endogenous and exogenous attention in touch.

    Science.gov (United States)

    Jones, Alexander; Forster, Bettina

    2013-12-01

    Endogenous and exogenous attention in touch have typically been investigated separately. Here we use a double-cueing paradigm manipulating both types of orienting in each trial. Bilateral endogenous cues induced long-lasting facilitation of endogenous attention up to 2 s. However, the exogenous cue only elicited an effect at short intervals. Our results favour a supramodal account of attention and this study provides new insight into how endogenous and exogenous attention operates in the tactile modality.

  9. Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study

    Directory of Open Access Journals (Sweden)

    Daniel Chavarria-Bolaños

    2015-01-01

    Full Text Available Purpose. This study quantified the expression of substance P (SP, calcitonin gene-related peptide (CGRP, β-endorphins (β-End, and methionine-enkephalin (Met-Enk in human dental pulp following orthodontic intrusion. Methods. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg, which would undergo controlled intrusive force for seven days, and the control group (CTRg, which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA. Results. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. Conclusions. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain.

  10. Further identification of endogenous gibberellins in the shoots of pea, line G2

    International Nuclear Information System (INIS)

    Halinska, A.; Davies, P.J.; Lee, J.W.; Zhu, Yuxian

    1989-01-01

    To interpret the metabolism of radiolabeled gibberellins A 12 -aldehyde and A 12 in shoots of pea (Pisum sativum L.), the identity of the radiolabeled peaks has to be determined and the endogenous presence of the gibberellins demonstrated. High specific activity [ 14 C]GA 12 and [ 14 C]GA 12 -aldehyde were synthesized using a pumpkin endosperm enzyme preparation, and purified by high performance liquid chromatography (HPLC). [ 14 C]GA 12 was supplied to upper shoots of pea, line G2, to produce radiolabeled metabolites on the 13-OH pathway. Endogenous compounds copurifying with the [ 14 C]GAs on HPLC were analyzed by gas chromatography-mass spectrometry. The endogenous presence of GA 53 , GA 44 , GA 19 and GA 20 was demonstrated and their HPLC peak identity ascertained. The 14 C was progressively diluted in GAs further down the pathway, proportional to the levels found in the tissue and inversely proportional to the speed of metabolism, ranging from 63% in GA 53 to 4% in GA 20 . Calculated levels of GA 20 , GA 19 , GA 44 , and GA 53 were 42, 8, 10, and 0.5 nanograms/gram, respectively

  11. Endogenous versus exogenous shocks in systems with memory

    Science.gov (United States)

    Sornette, D.; Helmstetter, A.

    2003-02-01

    Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

  12. Postoperative serum levels of Endocan are associated with the duration of norepinephrine support after coronary artery bypass surgery.

    Science.gov (United States)

    Bouglé, Adrien; Allain, Pierre-Antoine; Favard, Séverine; Ait Hamou, Nora; Carillion, Aude; Leprince, Pascal; Granger, Benjamin; Amour, Julien

    2018-02-21

    Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response and an endothelial dysfunction, whose qualitative assessment appears to be a major issue. Endocan (ESM-1, endothelial cell specific molecule-1) is a protein preferentially expressed by the endothelium and previously associated with prognosis of septic shock or acute respiratory distress syndrome. In this pilot study, we investigated the kinetic of Endocan in planned coronary artery bypass grafting (CABG) surgery with CPB. We conducted an observational, prospective, mono centre study. All adult patients with left systolic ejection fraction>50%, undergoing planned on-pump CABG, were screened for inclusion. A written informed consent was obtained. Measurements and main results Serum Endocan concentrations were respectively 2.4 [2.1-3.0] ng. mL -1 , 10.4 [7.4-13.9] ng.mL -1 , 5.7 [4.4-8.2] ng.mL -1 , and 5.4 [4.1-7.5] ng.mL -1 at day 0, day 1, day 3 and day 5. Endocan concentrations increased at day 1, day 3, and day 5 in comparison with preoperative concentration (P<0.001). In the multivariate analysis, age (P=0.002), history of acute coronary syndrome (P=0.024) and the catecholamine-free days at day 28 (P=0.007) were associated to the increase of perioperative Endocan concentrations. Serum Endocan concentration increases after CABG surgery with CPB until day 1. The norepinephrine support increases the risk of Endocan release, suggesting a relationship between the kinetic of Endocan and the vasoplegic syndrome. At day 3, Endocan concentration decreases slowly but is not normalised at day 5. Further studies should investigate the prognostic value of the magnitude of postoperative Endocan concentration after cardiac surgery. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  13. Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice.

    Science.gov (United States)

    van der Geest, Rick; Ouweneel, Amber B; van der Sluis, Ronald J; Groen, Albert K; Van Eck, Miranda; Hoekstra, Menno

    2016-09-01

    Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18±5ng/ml vs 472±58ng/ml; Phypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin

    Science.gov (United States)

    Laferrère, Blandine; Abraham, Cynthia; Awad, Marianne; Jean-Baptiste, Stephanie; Hart, Allison B.; Garcia-Lorda, Pilar; Kokkoris, Peter; Russell, Colleen D.

    2010-01-01

    Context Administration of glucocorticoids increases serum leptin levels in lean and obese individuals. A morning meal produces an increase in insulin, a cortisol peak, and an increase in leptin; these changes do not occur during fasting. Objective The objective of this study was to investigate whether inhibiting endogenous cortisol secretion with metyrapone decreases 24-h serum leptin levels and to determine whether a meal-related midmorning surge in cortisol is a prerequisite for the meal-entrained nocturnal rise in leptin. Design This was a randomized, cross-over study. Setting The study was performed at the General Clinical Research Center. Participants Lean males were studied. Intervention In study 1, seven lean men were studied for 24 h while their endogenous cortisol secretions were manipulated as follows: 1) CONTROL; 2) cortisol suppression by metyrapone (MET); and 3) MET and oral hydrocortisone (at 0900 h) (MET + CORT). Subjects were all fed a eucaloric diet (two meals at 1100 and 1700 h). In study 2, six men were studied without pharmacological intervention for 24 h on two occasions: once under a complete fast (FAST) and once in a feeding condition (one meal at 1100 h; FED). Main Outcome Measure The main outcome measure was serum leptin. Results MET significantly suppressed serum cortisol at 0800 h, midmorning, and over the 24-h period. As a result of cortisol suppression, 24-h serum leptin levels were decreased vs. control values despite similar insulin responses to meals. Administering a single dose of hydrocortisone to MET subjects potently stimulated serum leptin compared with the effect of MET alone. Conclusions Our data demonstrate that endogenous cortisol secretion is necessary for the maintenance of serum leptin levels over 24 h in lean, normally fed males. PMID:16537679

  15. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  16. Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

    Science.gov (United States)

    Yang, H; Raizada, M K

    1999-04-01

    Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

  17. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  18. International Environmental Agreements with Endogenous or Exogenous Risk

    OpenAIRE

    Fuhai Hong; Larry Karp

    2014-01-01

    We examine the effect of endogenous and exogenous risk on the equilibrium (expected) membership of an International Environmental Agreement when countries are risk averse. Endogenous risk arises when countries use mixed rather than pure strategies at the participation game, and exogenous risk arises from the inherent uncertainty about the costs and benefits of increased abate- ment. Under endogenous risk, an increase in risk aversion increases expected participation. Under exogenous risk and ...

  19. Isolating the Norepinephrine Pathway Comparing Lithium in Bipolar Patients to SSRIs in Depressive Patients

    Directory of Open Access Journals (Sweden)

    Andy R. Eugene

    2015-07-01

    Full Text Available Introduction: The purpose of this investigatory neuroimaging analysis was done to better understand the pharmacodynamics of Lithium by isolating the norepinephrine pathway in the brain. To accomplish this, we compared patients with Bipolar Disorder treated with Lithium to patients diagnosed with Major Depression or Depressive Disorder who are treated with Selective Serotonin Reuptake Inhibitors (SSRIs.Methodology: We used Standardized Low Resolution Brain Electrotomography to calculate the whole brain, voxel-by-voxel, unpaired t-tests Statistical non-Parametric Maps. For our first electrophysiological neuroimaging investigation, we compared 46 patients (average age = 34 ± 16.5 diagnosed with Bipolar Affective Disorder to three patient groups all diagnosed with Major Depression or Depressive Episode. The first is with 48 patients diagnosed with Major Depression or Depressive Episode (average age = 49 ± 12.9, the second to 16 male depressive patients (average age = 45 ± 15.1, and the final comparison to 32 depressive females (average age = 50 ± 11.7.Results: The results of sLORETA three-dimensional statistical non-parametric maps illustrated that Lithium influenced an increase in neurotransmission in the right Superior TemporalGyrus (t=1.403, p=0.00780, Fusiform Gyrus (t=1.26, and Parahippocampal Gyrus (t=1.29.Moreover, an increased in neuronal function was found was also identified at the Cingulate Gyrus(t=1.06, p=0.01200.Conclusion: We are proposing a translational clinical biological marker for patients diagnosed with Bipolar Disorder to guide physicians during the course of Lithium therapy and have identified neuroanatomical structures influenced by norepinephrine.

  20. 3H-dopamine accumulation by rat brain synaptic vesicles in a membrane-impermeable medium.

    Science.gov (United States)

    Gershten, M J; Disbrow, J K; Ruth, J A

    1983-07-25

    3H-Dopamine (DA) accumulation by storage vesicles from whole rat brain was significantly stablized in a buffer system based upon the membrane-impermeant D-potassium tartrate. 3H-DA uptake saturated by twenty minutes (Km 2.1 X 10(-5)M) and remained stable for periods of 40-60 minutes. Accumulated DA was rapidly exchangeable with exogenous DA. Total levels of accumulation (pmol/mg protein) were 41.7 +/- 2.9 (37 degrees), 11.9 +/- 2.5 (4 degrees), 31.3 +/- 1.8 (absence of ATP), 26.3 +/- 2.7 (reserpine, 10(-6)M), 26.1 +/- 0.67 (no ATP + reserpine 10(-6), and 14.6 +/- 2.4 (carbonylcyanide-p-triflouromethoxyphenylhydrazone, FCCP, 10(-6)M). Depletion of endogenous DA levels by pretreatment of the animals with alpha-methyl-p-tyrosine greatly diminished the reserpine-insensitive DA accumulation. After depletion of endogenous DA, ATP-independent uptake was significantly retarded, but eventually reached near-control levels. This uptake was abolished in the presence of FCCP (10(-6)M). The results suggest that endogenous levels of DA and ATP contribute to the reserpine- and ATP-insensitive DA accumulation observed in vesicles from untreated animals. HPLC analysis demonstrated no conversion of DA to norepinephrine (NE) in the course of the experiments.

  1. Endogenous TSH levels at the time of 131I ablation do not influence ablation success, recurrence-free survival or differentiated thyroid cancer-related mortality

    International Nuclear Information System (INIS)

    Vrachimis, Alexis; Riemann, Burkhard; Maeder, Uwe; Reiners, Christoph; Verburg, Frederik A.

    2016-01-01

    Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative 131 I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant 131 I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates (p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant (p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.53). The precise endogenous TSH levels at the time of 131 I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of 131 I ablation can be discarded. (orig.)

  2. Investigation of endogenous soybean food allergens by using a 2-dimensional gel electrophoresis approach.

    Science.gov (United States)

    Rouquié, David; Capt, Annabelle; Eby, William H; Sekar, Vaithilingam; Hérouet-Guicheney, Corinne

    2010-12-01

    As part of the safety assessment of genetically modified (GM) soybean, 2-dimensional gel electrophoresis analyses were performed with the isoxaflutole and glyphosate tolerant soybean FG72, its non-GM near-isogenic counterpart (Jack) and three commercial non-GM soybean lines. The objective was to compare the known endogenous human food allergens in seeds in the five different soybean lines in order to evaluate any potential unintended effect(s) of the genetic modification. In total, 37 protein spots representing five well known soybean food allergen groups were quantified in each genotype. Qualitatively, all the allergenic proteins were detected in the different genetic backgrounds. Quantitatively, among 37 protein spots, the levels of accumulation of three allergens were slightly lower in the GM soybean than in the non-GM counterparts. Specifically, while the levels of two of these three allergens fell within the normal range of variation observed in the four non-GM varieties, the level of the third allergen was slightly below the normal range. Overall, there was no significant increase in the level of allergens in FG72 soybean seeds. Therefore, the FG72 soybean can be considered as safe as its non-GM counterpart with regards to endogenous allergenicity. Additional research is needed to evaluate the biological variability in the levels of endogenous soybean allergens and the correlation between level of allergens and allergenic potential in order to improve the interpretation of these data in the safety assessment of GM soybean context. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

    Science.gov (United States)

    Gue, Ying X; Gorog, Diana A

    2017-08-25

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

  4. Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus-K (HERV-K) in psoriasis.

    Science.gov (United States)

    Gupta, Rashmi; Michaud, Henri-Alexandre; Zeng, Xue; Debbaneh, Maya; Arron, Sarah T; Jones, R Brad; Ormsby, Christopher E; Nixon, Douglas F; Liao, Wilson

    2014-09-16

    Psoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world's population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis. In the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls. In psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin. Together, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.

  5. Bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Skovlund; Prause, Jan Ulrik; Kiilgaard, Jens Folke

    2014-01-01

    Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient.......Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient....

  6. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Lopez, David S; Advani, Shailesh; Tsilidis, Konstantinos K; Wang, Run; Canfield, Steven

    2017-06-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990-2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  7. Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

    Science.gov (United States)

    Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

    2017-09-01

    Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Productivity and Unemployment in a Two-country Model with Endogenous Growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1997-01-01

    Relative to the United States, most European countries have high rates of unemployment and low levels of productivity in manufacturing. To relate these issues, we develop a leader-follower model with endogenous growth and dual labour markets, stressing the role of high-tech and high-wage sectors in

  9. The Endogenous-Exogenous Partition in Attribution Theory

    Science.gov (United States)

    Kruglanski, Arie W.

    1975-01-01

    Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

  10. Endogenous Markups, Firm Productivity and International Trade:

    DEFF Research Database (Denmark)

    Bellone, Flora; Musso, Patrick; Nesta, Lionel

    ) markups are positively related to firm productivity; 3) markups are negatively related to import penetration; 4) markups are positively related to firm export intensity and markups are higher on the export market than on the domestic ones in the presence of trade barriers and/or if competitors...... on the export market are less efficient than competitors on the domestic market. We estimate micro-level price cost margins (PCMs) using firm-level data extending the techniques developed by Hall (1986, 1988) and extended by Domowitz et al. (1988) and Roeger (1995) for the French manufacturing industry from......In this paper, we test key micro-level theoretical predictions ofMelitz and Ottaviano (MO) (2008), a model of international trade with heterogenous firms and endogenous mark-ups. At the firm-level, the MO model predicts that: 1) firm markups are negatively related to domestic market size; 2...

  11. THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

    Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

  12. Endogenous fishing mortalities: a state-space bioeconomic model

    OpenAIRE

    DA-ROCHA JOSÉ MARIA; GARCÍA-CUTRÍN JAVIER; GUTIÉRREZ MARÍA-JOSÉ; GAMITO JARDIM JOSÉ ERNESTO

    2017-01-01

    A methodology that endogenously determines catchability functions that link fishing mortality with contemporaneous stock abundance is presented. We consider a stochastic age-structured model for a fishery composed by a number of fishing units (fleets, vessels or métiers) that optimally select the level of fishing effort to be applied considering total mortalities as given. The introduction of a balance constrain which guarantees that total mortality is equal to the sum of individual fishing m...

  13. Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

    Science.gov (United States)

    E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

  14. Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.

    Science.gov (United States)

    Angelici, Bartolomeo; Mailand, Erik; Haefliger, Benjamin; Benenson, Yaakov

    2016-08-30

    One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion

    DEFF Research Database (Denmark)

    Mortensen, Stefan P.; Gonzalez-Alonso, Jose; Nielsen, Jens Jung

    2009-01-01

    ATP and NE concentrations to gain insight into the interstitial and intravascular mechanisms by which ATP causes muscle vasodilation and sympatholysis. Leg hemodynamics and muscle interstitial nucleotide and norepinephrine (NE) concentrations were measured during: 1) femoral arterial ATP infusion (0......, respectively (Pcontracting muscle (Pmuscle, whereas interstitial NE concentrations increased similarly in both active...... and inactive muscles. These results suggest that the vasodilatory and sympatholytic effects of intraluminal ATP are mainly mediated via endothelial prinergic receptors. Intraluminal ATP and muscle contractions appear to modulate sympathetic nerve activity by inhibiting the effect of NE rather than blunting its...

  16. Psychological rehabilitation of patients with endogenous disease

    Directory of Open Access Journals (Sweden)

    Tamara Kryvonis

    2013-07-01

    Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.

  17. Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers

    Directory of Open Access Journals (Sweden)

    Yansong eLi

    2014-03-01

    Full Text Available Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs, we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.

  18. Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers.

    Science.gov (United States)

    Li, Yansong; Sescousse, Guillaume; Dreher, Jean-Claude

    2014-01-01

    Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs), we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI) and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.

  19. Endogenous antispermatogenic agents: prospects for male contraception.

    Science.gov (United States)

    Ewing, L L; Robaire, B

    1978-01-01

    A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.

  20. Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

    International Nuclear Information System (INIS)

    Geest, Rick van der; Ouweneel, Amber B.; Sluis, Ronald J. van der; Groen, Albert K.; Van Eck, Miranda; Hoekstra, Menno

    2016-01-01

    Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

  1. Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Geest, Rick van der, E-mail: r.van.der.geest@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Ouweneel, Amber B., E-mail: a.b.ouweneel@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Sluis, Ronald J. van der, E-mail: r.vandersluis@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Groen, Albert K., E-mail: a.k.groen@umcg.nl [University Medical Center Groningen (Netherlands); Van Eck, Miranda, E-mail: m.eck@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Hoekstra, Menno, E-mail: hoekstra@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands)

    2016-09-01

    Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

  2. The endogenous preproglucagon system is not essential for gut growth homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Pernille Wismann

    2017-07-01

    Conclusion: The present study indicates that the endogenous preproglucagon system, exemplified by the entire GCG gene and the receptors for GLP-1 and GLP-2, does not play a major role in normal gut development in the mouse. Furthermore, elevation in local intestinal and circulating levels of GLP-1 and GLP-2 achieved after VSG has limited impact on intestinal morphometry. Hence, although exogenous treatment with GLP-1 and GLP-2 analogs enhances gut growth, the contributions of endogenously-secreted GLP-1 and GLP-2 to gut growth may be more modest and highly context-dependent.

  3. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  4. Investigation of ionizing sublethal doses effects on endogenous radioresistance background

    International Nuclear Information System (INIS)

    Kudryashov, Yu.B.; Goncharenko, E.N.; Antonova, S.V.; Akhalaya, M.Ya.; Bajzhumanov, A.A.; Shestakova, S.V.

    1997-01-01

    Sublethal doses of X-radiation (0.5 Gy and 1 Gy) caused the alterations in levels of main components of endogenous radioresistance background in rat tissues. There were demonstrated the decrease of serotonin content in stomach mocosa and spleen, adrenalin, noradrenalin and corticosteroids contents in adrenal glands, nonprotein thiols content in spleen and the increase of lipid peroxide level in serum on the 3-14 days after irradiation. The recovery of the investigated parameters was occurred to the 21 day after exposure. (author)

  5. A recombinant endogenous retrovirus amplified in a mouse neuroblastoma is involved in tumor growth in vivo.

    Science.gov (United States)

    Pothlichet, Julien; Heidmann, Thierry; Mangeney, Marianne

    2006-08-15

    The theory of immunoediting postulates that tumor cells exhibit a reduced immunogenicity to escape eradication by the host immune system. It has been proposed that endogenous retroviruses--provided that they are active--could play a role in this process, via the immunosuppressive domain carried by their envelope protein. Here, we demonstrate that the Neuro-2a tumor cell line--originating from a spontaneous A/J mouse neuroblastoma--produces an infectious retrovirus that most probably results from a recombination event between 2 mouse endogenous retroviral elements. This Neuro-2a-associated recombinant retrovirus derives from the unique ecotropic provirus located at the Emv-1 locus, but with a gag sequence conferring B-tropism, thus allowing its high-level amplification in Neuro-2a cells. We show that knocking down -by RNA interference- this endogenous retrovirus in Neuro-2a cells has no effect on the transformed phenotype of the cells, but results in delayed tumor growth and prolonged animal survival, following engraftment of the cells into immunocompetent mice. Recombination between endogenous retroviruses, amplification of the resulting element and high-level expression of its immunosuppressive activity are therefore likely steps of an immunoediting process, leading to an invading tumor. Copyright 2006 Wiley-Liss, Inc.

  6. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    The question presented in this article is how to improve the dispute resolution competence of practitioners in Africa. The response offered involves enhancing the endogenous knowledge of a dispute and how to resolve it. This requires not only an understanding of what endogenous knowledge is, but also an alignment of ...

  7. Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

    Directory of Open Access Journals (Sweden)

    Richard J. Ablin

    1987-01-01

    Full Text Available In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa, and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl and the synthetic oestrogen, diethylstiboestrol (DES, as representative endogenous and exogenous immunomodulatory factors (IMF of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy have been made by evaluating their effect on the lytic activity of natural killer (NK cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to

  8. Detection of endogenous lithium in neuropsychiatric disorders--a model for biological transmutation.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2002-01-01

    The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright 2002 John Wiley & Sons, Ltd.

  9. Song competition affects monoamine levels in sensory and motor forebrain regions of male Lincoln's sparrows (Melospiza lincolnii.

    Directory of Open Access Journals (Sweden)

    Kendra B Sewall

    Full Text Available Male animals often change their behavior in response to the level of competition for mates. Male Lincoln's sparrows (Melospiza lincolnii modulate their competitive singing over the period of a week as a function of the level of challenge associated with competitors' songs. Differences in song challenge and associated shifts in competitive state should be accompanied by neural changes, potentially in regions that regulate perception and song production. The monoamines mediate neural plasticity in response to environmental cues to achieve shifts in behavioral state. Therefore, using high pressure liquid chromatography with electrochemical detection, we compared levels of monoamines and their metabolites from male Lincoln's sparrows exposed to songs categorized as more or less challenging. We compared levels of norepinephrine and its principal metabolite in two perceptual regions of the auditory telencephalon, the caudomedial nidopallium and the caudomedial mesopallium (CMM, because this chemical is implicated in modulating auditory sensitivity to song. We also measured the levels of dopamine and its principal metabolite in two song control nuclei, area X and the robust nucleus of the arcopallium (RA, because dopamine is implicated in regulating song output. We measured the levels of serotonin and its principal metabolite in all four brain regions because this monoamine is implicated in perception and behavioral output and is found throughout the avian forebrain. After controlling for recent singing, we found that males exposed to more challenging song had higher levels of norepinephrine metabolite in the CMM and lower levels of serotonin in the RA. Collectively, these findings are consistent with norepinephrine in perceptual brain regions and serotonin in song control regions contributing to neuroplasticity that underlies socially-induced changes in behavioral state.

  10. Immunoassay of serum alpha-1 antitrypsin level in uveitis.

    OpenAIRE

    Gupta, A K; Sarin, G S

    1984-01-01

    The serum alpha-1 antitrypsin level was measured in 60 patients with endogenous uveitis, 27 patients with phacoallergic endophthalmitis, 12 patients with phacolytic glaucoma, and 58 healthy subjects. Thirty-four patients with endogenous uveitis were also followed up for 6 months after treatment, and the serum alpha-1 antitrypsin level was measured again. There was a significant rise in the serum alpha-1 antitrypsin level in cases of endogenous uveitis and phacoallergic endophthalmitis but no ...

  11. Neurochemical Correlates of Autistic Disorder: A Review of the Literature

    Science.gov (United States)

    Lam, Kristen S. L.; Aman, Michael G.; Arnold, L. Eugene

    2006-01-01

    Review of neurochemical investigations in autistic disorder revealed that a wide array of transmitter systems have been studied, including serotonin, dopamine, norepinephrine, acetylcholine, oxytocin, endogenous opioids, cortisol, glutamate, and gamma-aminobutyric acid (GABA). These studies have been complicated by the fact that autism is a very…

  12. How Stock Markets Development Affect Endogenous Growth Theory

    Directory of Open Access Journals (Sweden)

    Najeb Masoud

    2013-10-01

    Full Text Available This paper can bedescribed as a significant exploratory study that will provide a significantcontribution to knowledge to consider crucial issues which need to be barriersto understanding or a temptation/ requirement to judge some practices as‘better’ than others for stock market development effective approach andimplement successful stock market performance and economic growth. Recentanalysis of the link between financial development and growth, gained frominsights acquired as a result of using the technique of endogenous growthmodels, has illustrated that growth without exogenous technical progress andthat growth rates could be related to technology, income distribution andinstitutional arrangements. This provides the theoretical background thatempirical studies have lacked; illustrating that financial intermediationaffects the level of economic growth. Resulting models have provided newimpetus to empirical research of the effects of financial development. Thebirth of the new endogenous growth theory has facilitated the development ofimproved growth models where the long-term rate could be affected by a numberof elements. These included technology, education and health policies in theprocess of economic development, capital accumulation, government policies andinstitutional activities in the role of financial development in economicgrowth.

  13. From Gender as Exogenous to Gender as Endogenous in the New Economics

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2011-01-01

    textabstractThis chapter argues that gender is endogenous to the economic process. It demonstrates a two-way relationship between the economy and gender relations, and emphasizes the macro level. It demonstrates that inequality in gender relations can have a negative effect on economic policy and

  14. Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

    Science.gov (United States)

    McKillip, Jack

    Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

  15. Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression.

    Science.gov (United States)

    Denzler, Rémy; McGeary, Sean E; Title, Alexandra C; Agarwal, Vikram; Bartel, David P; Stoffel, Markus

    2016-11-03

    Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent of repression, they have little effect on the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ∼20% of that observed for canonical 8-nt sites. In aggregate, low-affinity/background sites also contribute to competition. Sites with extensive additional complementarity can appear as more potent, but only because they induce miRNA degradation. Cooperative binding of proximal sites for the same or different miRNAs does increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNAs and target abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene regulation, and the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  17. Diurnal trend in EEG interhemispheric asymmetry in endogenous depressions

    Directory of Open Access Journals (Sweden)

    T S Melnikova

    2011-01-01

    Full Text Available A trend in EEG interhemispheric asymmetry was studied in patients with endogenous depressions in morning and evening hours. In the morning, the spectral power of alpha rhythm particularly in the occipital cortical regions, proved to be higher than that in the evening. In the morning, the interhemispheric differences in the power of occipital alpha rhythm were leveled off while in the evening there was normalization of interhemispheric balance with the higher power of alpha rhythm in the right occipital region. Analysis of the mean coherence (mean Coh of alpha rhythm in individual cortical regions revealed that the patients with endogenous depression had higher readings mainly in the parietal and central regions of both hemispheres and in the right temporal regions in the morning than in the evening. The occipital and posttemporal regions showed an inverse trend in the mean Coh - it was lower in the morning than in the evening

  18. Endogenous TSH levels at the time of {sup 131}I ablation do not influence ablation success, recurrence-free survival or differentiated thyroid cancer-related mortality

    Energy Technology Data Exchange (ETDEWEB)

    Vrachimis, Alexis; Riemann, Burkhard [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Maeder, Uwe; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); RWTH University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2016-02-15

    Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative {sup 131}I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant {sup 131}I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates (p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant (p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.53). The precise endogenous TSH levels at the time of {sup 131}I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of {sup 131}I ablation can be discarded. (orig.)

  19. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Gudz', T.I.; Zolotareva, L.T.; Kovaleva, Z.I.; Peshkova, E.N.

    1978-01-01

    It is shown that in Saccharomyces cerevisiae of ''wild type'' diploid cells (more radioresistant than haploid ones) are characterized by a higher content of endogenous biologically active substances, which possess a radioprotective ability (biogenous amines and SOD), and a lower level of radiosensitizing substances (hydroperoxides of higher unsaturated fatty acids). With Saccharomyces cerevisiae, bearing mutation rad 51, not all the components of the radioresistance background shoW this dependence, which is indicative of the presence of additional factors affecting radioresistance of these cells

  20. Endogenous reverse transcriptase (RT) activity and Chromatin remodeling in normal and transformed cells and early embryos

    International Nuclear Information System (INIS)

    Spadafora, C.; Sciamanna, I.; Misteli, T.

    2009-01-01

    Endogenous Reverse Transcriptase (RT) is an enzyme encoded by two classes of genomic retro-elements: retro-transposons and endogenous retroviruses. Basal levels of RT are expressed in all non pathological, differentiated tissues while high RT expression levels characterize tumorigenic cells, germ cells and embryonic tissues. Preliminary studies carried out in our laboratory have shown that RT inhibition using pharmacological inhibitors (nevirapine and efavirenz, two drugs currently used in AIDS therapy) drastically reduces cell proliferation, promotes differentiation of tumorigenic cells in vitro, induces a reprogrammed gene expression and antagonizes tumor progression in nude mice inoculated with tumorigenic human cell lines, including melanoma, prostate and colon carcinoma and microcitoma

  1. Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt.

    Science.gov (United States)

    Chen, Ye; Liang, Yuzhen; Hu, Tingting; Wei, Riming; Cai, Congjie; Wang, Ping; Wang, Lingyu; Qiao, Wei; Feng, Leping

    2017-11-01

    Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro , is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (Pendogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (Pendogenous Nampt upregulation may be critical in the treatment of DN pro-inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.

  2. Monoamine levels in the nucleus accumbens correlate with male sexual behavior in middle-aged rats.

    Science.gov (United States)

    Tsai, Houng-Wei; Shui, Hao-Ai; Liu, Hang-Shen; Tai, Mei-Yun; Tsai, Yuan-Feen

    2006-02-01

    The correlation between monoamine levels in the nucleus accumbens (NAcc) and male sexual behavior was studied in middle-aged rats. Male rats (18-19months) were assigned to three groups: (1) Group MIE consisted of rats showing mounts, intromissions, and ejaculations; (2) Group MI was composed of rats showing mounts and intromissions, but no ejaculation; and (3) Group NC were non-copulators showing no sexual behavior. Young adult rats (4-5months), displaying complete copulatory behavior, were used as the control group. Levels of dopamine (DA), serotonin, and norepinephrine and their metabolites in the NAcc were measured by high-pressure liquid chromatography with electrochemical detection. No difference was seen in DA levels between MIE rats and young controls, whereas DA levels in NC rats were significantly lower than those in both MIE and MI rats. Serotonin levels in NC rats were significantly higher than those in MIE and MI rats. Conversely, norepinephrine levels in NC rats were lower than those in MIE rats. These results suggest that monoamine levels in the NAcc correlate with sexual performance in male rats and that changes in NAcc monoamine levels might affect male sexual behavior in middle-aged rats.

  3. Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy

    Directory of Open Access Journals (Sweden)

    Emiliano eMacaluso

    2013-10-01

    Full Text Available The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the ventral fronto-parietal networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions.

  4. Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy

    Science.gov (United States)

    Macaluso, Emiliano; Doricchi, Fabrizio

    2013-01-01

    The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions. PMID:24155707

  5. Quantifying the timescales over which exogenous and endogenous conditions affect soil respiration.

    Science.gov (United States)

    Barron-Gafford, Greg A; Cable, Jessica M; Bentley, Lisa Patrick; Scott, Russell L; Huxman, Travis E; Jenerette, G Darrel; Ogle, Kiona

    2014-04-01

    Understanding how exogenous and endogenous factors and above-ground-below-ground linkages modulate carbon dynamics is difficult because of the influences of antecedent conditions. For example, there are variable lags between above-ground assimilation and below-ground efflux, and the duration of antecedent periods are often arbitrarily assigned. Nonetheless, developing models linking above- and below-ground processes is crucial for estimating current and future carbon dynamics. We collected data on leaf-level photosynthesis (Asat ) and soil respiration (Rsoil ) in different microhabitats (under shrubs vs under bunchgrasses) in the Sonoran Desert. We evaluated timescales over which endogenous and exogenous factors control Rsoil by analyzing data in the context of a semimechanistic temperature-response model of Rsoil that incorporated effects of antecedent exogenous (soil water) and endogenous (Asat ) conditions. For both microhabitats, antecedent soil water and Asat significantly affected Rsoil , but Rsoil under shrubs was more sensitive to Asat than that under bunchgrasses. Photosynthetic rates 1 and 3 d before the Rsoil measurement were most important in determining current-day Rsoil under bunchgrasses and shrubs, respectively, indicating a significant lag effect. Endogenous and exogenous controls are critical drivers of Rsoil , but the relative importance and the timescale over which each factor affects Rsoil depends on above-ground vegetation and ecosystem structure characteristics. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  6. Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy.

    Science.gov (United States)

    Macaluso, Emiliano; Doricchi, Fabrizio

    2013-01-01

    The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions.

  7. Endogene CGRP

    OpenAIRE

    Höfer, Martina

    2010-01-01

    Hintergrund und Ziele Die vorliegende tierexperimentelle Arbeit beschäftigt sich mit der Frage, welche Rolle endogenes Calcitonin-gene related peptide (CGRP) in der Niere spielt. Hierbei untersuchten wir die renale CGRP Freisetzung aus renalen Afferenzen in vitro anhand von gesunden Tieren und einem pathologischen Modell der Glomerulonephritis. Man weiß bereits, dass sowohl sympathische als auch primär sensorische Neuronen die Entzündung und die Immunantwort in der Peripherie regulieren (68)....

  8. [The endogenous opioid system and drug addiction].

    Science.gov (United States)

    Maldonado, R

    2010-01-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  9. Digoxin-like immunoreactivity, endogeneous cardiac glycoside-like factors (s) and natriuretic hormone

    International Nuclear Information System (INIS)

    Clerico, A.

    1987-01-01

    Endogenous factors crossreacting with antidigoxin antibodies (digoxin-like immunoreactive substances=DLIS) have been found in several tissues and body fluids of animals and humans, using commercially avaiable digoxin RIA or EIA methods. Detectable DLIS concentration were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that DLIS could be a substance with low molecular weight. Experimental studies and theoretical consideration suggest that DLIS, in addition to reacting with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na + /K + ATPase (sodium pump). Therefore, it has been suggested that DLSI is an endogeneous modulator of the membrane sodium-potassium pump and it could play a role in the regulation of fluid and electrolytes muscular tone of myocardial and also in pathogenesis of hypertension

  10. Endogenous Money Supply and Money Demand

    OpenAIRE

    Woon Gyu Choi; Seonghwan Oh

    2000-01-01

    This paper explores the behavior of money demand by explicitly accounting for the money supply endogeneity arising from endogenous monetary policy and financial innovations. Our theoretical analysis indicates that money supply factors matter in the money demand function when the money supply partially responds to money demand. Our empirical results with U.S. data provide strong evidence for the relevance of the policy stance to the demand for MI under a regime in which monetary policy is subs...

  11. Optimized endogenous post-stratification in forest inventories

    Science.gov (United States)

    Paul L. Patterson

    2012-01-01

    An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

  12. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

    Science.gov (United States)

    Layé, S; Gheusi, G; Cremona, S; Combe, C; Kelley, K; Dantzer, R; Parnet, P

    2000-07-01

    The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

  13. Optimal income taxation with endogenous participation and search unemployment

    OpenAIRE

    Lehmann, Etienne; Parmentier, Alexis; van der Linden, Bruno

    2011-01-01

    This paper characterizes the optimal redistributive taxation when individuals are hetero- geneous in two exogenous dimensions: their skills and their values of non-market activities. Search-matching frictions on the labor markets create unemployment. Wages, labor demand and participation are endogenous. The government only observes wage levels. Under a Max- imin objective, if the elasticity of participation decreases along the distribution of skills, at the optimum, the average tax rate is in...

  14. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Advani, Shailesh; Tsilidis, Konstantinos K.; Wang, Run; Canfield, Steven

    2017-01-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  15. Endogenous opioids regulate moment-to-moment neuronal communication and excitability

    Science.gov (United States)

    Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.

    2017-01-01

    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

  16. Endogenous retroviruses mobilized during friend murine leukemia virus infection.

    Science.gov (United States)

    Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H

    2016-12-01

    We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.

  17. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats

    DEFF Research Database (Denmark)

    Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul

    2002-01-01

    in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...

  18. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

  19. Lack of effect of norepinephrine on cranial haemodynamics and headache in healthy volunteers

    DEFF Research Database (Denmark)

    Lindholt, M; Petersen, K A; Tvedskov, J F

    2009-01-01

    Stress is a provoking factor for both tension-type headache and migraine attacks. In the present single-blind study, we investigated if stress induced by norepinephrine (NE) could elicit delayed headache in 10 healthy subjects and recorded the cranial arterial responses. NE at a dose of 0...... no changes in these arterial parameters after NE. In both treatment groups three subjects developed delayed headaches. Thus, stress by NE infusion did not result in delayed headache........025 microg kg(-1) min(-1) or placebo was infused for 90 min and the headache was followed for 14 h. Blood flow velocity in the middle cerebral artery (measured with transcranial Doppler) and diameters of the temporal artery and the radial artery (measured with ultrasound) were followed for 2 h. There were...

  20. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

  1. Exercise induced asthma and endogenous opioids.

    Science.gov (United States)

    Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

    1986-01-01

    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

  2. Effect of adeturone on the concentration of endogenous sulfhydryl groups in mouse spleen and liver

    International Nuclear Information System (INIS)

    Pantev, T.; Bychvarova, K.

    1981-01-01

    Levels of endogenous sulfhydryl groups (total, protein, and non-protein) in mouse liver and spleen were studied for response to the radioprotective drug Adeturone (AET adenosine triphosphate) as recorded at various time intervals (5 - 90 min) following administration of a 300 mg/kg b.w. dose. Spleen sulfhydryl concentration levels tended to elevation, with the peak effect noted at 45 min post-treatment. In the liver, augmentation was observed only for non-protein sylfhydryl groups, at 10 and 15 min post-treatment (time intervals when Adeturone affords maximum protection against radiation); at the 60 min, however, there was a statistically reliable drop. The findings indicate that Adeturone treatment produces response patterns of opposite directions in liver and spleen endogenous thiols. (A.B.)

  3. Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter

    International Nuclear Information System (INIS)

    Wilson, Alan A.; Patrick Johnson, David; Mozley, David; Hussey, Doug; Ginovart, Nathalie; Nobrega, Jose; Garcia, Armando; Meyer, Jeffery; Houle, Sylvain

    2003-01-01

    The (R,R) and (S,S) enantiomers of 2-[(2-methoxyphenoxy)phenylmethyl]morpholine (MeNER) have been radiolabelled with carbon-11 in good yield and at high specific activity. These radiotracers are close analogues of reboxetine, a potent and selective ligand for the norepinephrine transporter (NET). They were examined as potential ligands for imaging NET in vivo by positron emission tomography (PET). The in vivo brain distribution of both [ 11 C]-labeled enantiomers were evaluated in rats. Following tail-vein injection of the (R,R)-enantiomer regional brain uptake and washout of radioactivity was homogeneous at all time points examined (5-60 min). In contrast, administration of the (S,S)-enantiomer produced a heterogeneous distribution of radioactivity in brain with highest uptake in the hypothalamus, a NET rich region, and lowest uptake in the striatum, a brain region devoid of NET. Hypothalamus to striatum ratios of 2.5 to one were achieved at 60 min post injection of (S,S)-[ 11 C]-MeNER. Pre-injection of the norepinephrine reuptake inhibitors, reboxetine or desipramine, reduced hypothalamus to striatum ratios to near unity while reuptake inhibitors of dopamine and serotonin had no significant effect on binding. In vitro autoradiography studies (rat brain slices) with (S,S)-[ 11 C]-MeNER produced a regional distribution pattern that was consistent with the reported distribution of NET. (S,S)-[ 11 C]-MeNER has the potential to be the first successful PET ligand to image NET

  4. Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Alan A. E-mail: aaw@camhpet.on.ca; Patrick Johnson, David; Mozley, David; Hussey, Doug; Ginovart, Nathalie; Nobrega, Jose; Garcia, Armando; Meyer, Jeffery; Houle, Sylvain

    2003-02-01

    The (R,R) and (S,S) enantiomers of 2-[(2-methoxyphenoxy)phenylmethyl]morpholine (MeNER) have been radiolabelled with carbon-11 in good yield and at high specific activity. These radiotracers are close analogues of reboxetine, a potent and selective ligand for the norepinephrine transporter (NET). They were examined as potential ligands for imaging NET in vivo by positron emission tomography (PET). The in vivo brain distribution of both [{sup 11}C]-labeled enantiomers were evaluated in rats. Following tail-vein injection of the (R,R)-enantiomer regional brain uptake and washout of radioactivity was homogeneous at all time points examined (5-60 min). In contrast, administration of the (S,S)-enantiomer produced a heterogeneous distribution of radioactivity in brain with highest uptake in the hypothalamus, a NET rich region, and lowest uptake in the striatum, a brain region devoid of NET. Hypothalamus to striatum ratios of 2.5 to one were achieved at 60 min post injection of (S,S)-[{sup 11}C]-MeNER. Pre-injection of the norepinephrine reuptake inhibitors, reboxetine or desipramine, reduced hypothalamus to striatum ratios to near unity while reuptake inhibitors of dopamine and serotonin had no significant effect on binding. In vitro autoradiography studies (rat brain slices) with (S,S)-[{sup 11}C]-MeNER produced a regional distribution pattern that was consistent with the reported distribution of NET. (S,S)-[{sup 11}C]-MeNER has the potential to be the first successful PET ligand to image NET.

  5. Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Signy Bendiksen

    2014-01-01

    Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

  6. MnTM-4-PyP modulates endogenous antioxidant responses and protects primary cortical neurons against oxidative stress.

    Science.gov (United States)

    Cheng, Kuo-Yuan; Guo, Fei; Lu, Jia-Qi; Cao, Yuan-Zhao; Wang, Tian-Chang; Yang, Qi; Xia, Qing

    2015-05-01

    Oxidative stress is a direct cause of injury in various neural diseases. Manganese porphyrins (MnPs), a large category of superoxide dismutase (SOD) mimics, shown universally to have effects in numerous neural disease models in vivo. Given their complex intracellular redox activities, detailed mechanisms underlying the biomedical efficacies are not fully elucidated. This study sought to investigate the regulation of endogenous antioxidant systems by a MnP (MnTM-4-PyP) and its role in the protection against neural oxidative stress. Primary cortical neurons were treated with MnTM-4-PyP prior to hydrogen peroxide-induced oxidative stress. MnTM-4-PyP increased cell viability, reduced intracellular level of reactive oxygen species, inhibited mitochondrial apoptotic pathway, and ameliorated endoplasmic reticulum function. The protein levels and activities of endogenous SODs were elevated, but not those of catalase. SOD2 transcription was promoted in a transcription factor-specific manner. Additionally, we found FOXO3A and Sirt3 levels also increased. These effects were not observed with MnTM-4-PyP alone. Induction of various levels of endogenous antioxidant responses by MnTM-4-PyP has indispensable functions in its protection for cortical neurons against hydrogen peroxide-induced oxidative stress. © 2014 John Wiley & Sons Ltd.

  7. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.

    Science.gov (United States)

    Fitzgerald, Paul J

    2013-10-13

    A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

  8. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

    Directory of Open Access Journals (Sweden)

    Paul J. Fitzgerald

    2013-01-01

    Full Text Available A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

  9. Consensus statement and research needs: the role of dopamine and norepinephrine in depression and antidepressant treatment.

    Science.gov (United States)

    Nutt, David J; Baldwin, David S; Clayton, Anita H; Elgie, Rodney; Lecrubier, Yves; Montejo, Angel L; Papakostas, George I; Souery, Daniel; Trivedi, Madhukar H; Tylee, Andre

    2006-01-01

    During a special session, the faculty identified several specific areas related to the role of dopamine and norepinephrine in depression and antidepressant treatment that either warrant the clinician's attention or are in need of more research. Areas of interest include fatigue and lethargy in depression, treatment strategies for treatment-resistant depression, the somatic presentation of depression, neurobiology of fatigue and its role in determining treatment, symptom rating scales, and sexual side effects. In addition, the faculty discussed the importance of patient psychoeducation and self-management as well as the ways in which disease models of depression affect treatment.

  10. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.

  11. Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

    Science.gov (United States)

    Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

    2014-01-01

    Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

  12. Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus.

    Science.gov (United States)

    Evans, Leonard H; Alamgir, A S M; Owens, Nick; Weber, Nick; Virtaneva, Kimmo; Barbian, Kent; Babar, Amenah; Malik, Frank; Rosenke, Kyle

    2009-03-01

    Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

  13. Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure.

    Science.gov (United States)

    Ogi, Hiroshi; Itoh, Kyoko; Ikegaya, Hiroshi; Fushiki, Shinji

    2015-09-01

    Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes. C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams. The IntelliCage behavioral experiments were conducted from P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions were measured by high performance liquid chromatography. Furthermore, the associations between the neurotransmitter levels and the behavioral indices were statistically analyzed. In females exposed to BPA, the GABA and Glu levels in almost all regions, and the NE levels in the cortex, hypothalamus and thalamus were higher than those in the controls. In males exposed to BPA, the GABA levels in the amygdala and hippocampus showed lower values, while Glu levels were higher in some regions, compared with the controls. In regard to the associations, the number of "diurnal corner visits without drinking" was correlated with the NE levels in the cortex and thalamus in females. The "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus in males. These results suggest that prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA and Glu systems, resulting in behavioral alterations. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. Effect of temperature on the floral scent emission and endogenous volatile profile of Petunia axillaris.

    Science.gov (United States)

    Sagae, Masanori; Oyama-Okubo, Naomi; Ando, Toshio; Marchesi, Eduardo; Nakayama, Masayoshi

    2008-01-01

    The floral scent emission and endogenous level of its components in Petunia axillaris under different conditions (20, 25, 30, and 35 degrees C) were investigated under the hypothesis that floral scent emission would be regulated by both metabolic and vaporization processes. The total endogenous amount of scent components decreased as the temperature increased, the total emission showing a peak at 30 degrees C. This decrease in endogenous amount was compensated for by increased vaporization, resulting in an increase of floral scent emission from 20 degrees C to 30 degrees C. The ambient temperature differently and independently influenced the metabolism and vaporization of the scent compounds, and differences in vapor pressure among the scent compounds were reduced as the temperature increased. These characteristics suggest the operation of an unknown regulator to change the vaporization of floral scent.

  15. Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

    Science.gov (United States)

    Jakeman, K J; Bird, C R; Thorpe, R; Smith, H; Sweet, C

    1991-03-01

    Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

  16. Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition.

    Science.gov (United States)

    Baglietto-Vargas, David; Kitazawa, Masashi; Le, Elaine J; Estrada-Hernandez, Tatiana; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Green, Kim N; LaFerla, Frank M

    2014-02-01

    Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. © 2013.

  17. Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding

    DEFF Research Database (Denmark)

    Frokjaer, Vibe G.; Erritzoe, David; Juul, Anders

    2010-01-01

    the effect of plasma sex hormone levels on neocortical 5-HT2A receptor binding as imaged with [18F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. Results: Mean neocortical 5-HT2A receptor binding was positively correlated with estradiol (p......Background: Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline...... levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT2A) receptor binding in men. Methods: In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6–81.7) we studied...

  18. Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory.

    Science.gov (United States)

    Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W

    2016-01-01

    Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots." At these NE hotspots, local glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. In contrast, arousal-induced LC activity inhibits less active representations via two mechanisms: 1) Where there are hotspots, lateral inhibition is amplified; 2) Where no hotspots emerge, NE levels are only high enough to activate low-threshold inhibitory adrenoreceptors. Thus, LC activation promotes a few hotspots of excitation in the context of widespread suppression, enhancing high priority representations while suppressing the rest. Hotspots also help synchronize oscillations across neural ensembles transmitting high-priority information. Furthermore, brain structures that detect stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during, or after encoding enhances synaptic plasticity at NE hotspots, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms promote selective attention and memory under arousal. GANE not only reconciles apparently contradictory findings in the emotion-cognition literature but also extends previous influential theories of LC neuromodulation by proposing specific mechanisms for how LC-NE activity increases neural gain.

  19. Endogenous fields enhanced stochastic resonance in a randomly coupled neuronal network

    International Nuclear Information System (INIS)

    Deng, Bin; Wang, Lin; Wang, Jiang; Wei, Xi-le; Yu, Hai-tao

    2014-01-01

    Highlights: • We study effects of endogenous fields on stochastic resonance in a neural network. • Stochastic resonance can be notably enhanced by endogenous field feedback. • Endogenous field feedback delay plays a vital role in stochastic resonance. • The parameters of low-passed filter play a subtle role in SR. - Abstract: Endogenous field, evoked by structured neuronal network activity in vivo, is correlated with many vital neuronal processes. In this paper, the effects of endogenous fields on stochastic resonance (SR) in a randomly connected neuronal network are investigated. The network consists of excitatory and inhibitory neurons and the axonal conduction delays between neurons are also considered. Numerical results elucidate that endogenous field feedback results in more rhythmic macroscope activation of the network for proper time delay and feedback coefficient. The response of the network to the weak periodic stimulation can be notably enhanced by endogenous field feedback. Moreover, the endogenous field feedback delay plays a vital role in SR. We reveal that appropriately tuned delays of the feedback can either induce the enhancement of SR, appearing at every integer multiple of the weak input signal’s oscillation period, or the depression of SR, appearing at every integer multiple of half the weak input signal’s oscillation period for the same feedback coefficient. Interestingly, the parameters of low-passed filter which is used in obtaining the endogenous field feedback signal play a subtle role in SR

  20. Endogenous Generalized Weights under DEA Control

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...

  1. Effects of aging and hypertension on the participation of endothelium-derived constricting factor (EDCF) in norepinephrine-induced contraction of rat femoral artery

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Petrová, M.; Karen, Petr; Kuneš, Jaroslav; Zicha, Josef

    2011-01-01

    Roč. 667, 1-3 (2011), s. 265-270 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : EDCF * SHR * norepinephrine * L-NNA * indomethacin Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.516, year: 2011

  2. [The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock].

    Science.gov (United States)

    Liang, F M; Yang, T; Dong, L; Hui, J J; Yan, J

    2017-05-01

    Objective: To assess whether dynamic arterial elastance(Ea(dyn))can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock. Methods: A prospective observational cohort study was conducted. Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University. Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO)monitoring technology before and after decreasing norepinephrine dosage. Ea(dyn) was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV). Mean arterial pressure(MAP) variation was calculated after decreasing the dose of NE. Response was defined as a ≥15% decrease of MAP. AUC was plotted to assess the value of Ea(dyn) in predicting MAP response. Results: A total of 32 patients were enrolled in our study, with 13 responding to NE dose decrease where as the other 19 did not. Ea(dyn) was lower in responders than in nonresponders (0.77±0.13 vs 1.09±0.31, P blood pressure variation, diastolic blood pressure variation, systemic vascular resistance variation and MAP variation( r =0.621, P =0.000; r =0.735, P =0.000; r =0.756, P =0.000; r =0.568, P =0.000 respectively). However, stoke volume variation, baseline level of systemic vascular resistance and NE baseline dose were not correlated with Ea(dyn) baseline value( r =0.264, P =0.076; r =0.078, P =0.545; r =0.002, P =0.987 respectively). Ea(dyn)≤0.97 predicted a decrease of MAP when decreasing NE dose, with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%. Conclusions: In septic shock patients treated with NE, Ea(dyn) is an index to predict the decrease of arterial pressure in response to NE dose reduction.

  3. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  4. Human endogenous retroviruses and ADHD.

    Science.gov (United States)

    Balestrieri, Emanuela; Pitzianti, Mariabernarda; Matteucci, Claudia; D'Agati, Elisa; Sorrentino, Roberta; Baratta, Antonia; Caterina, Rosa; Zenobi, Rossella; Curatolo, Paolo; Garaci, Enrico; Sinibaldi-Vallebona, Paola; Pasini, Augusto

    2014-08-01

    Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

  5. Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

    Directory of Open Access Journals (Sweden)

    Ewan eMcNay

    2015-11-01

    Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

  6. [Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

    Science.gov (United States)

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

    To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

  7. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

    Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

  8. Endogenous Retroviruses in the Genomics Era.

    Science.gov (United States)

    Johnson, Welkin E

    2015-11-01

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

  9. Exogenous and endogenous spatial attention effects on visuospatial working memory.

    Science.gov (United States)

    Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Lupiáñez, Juan; Belardinelli, Marta Olivetti

    2010-08-01

    In this study, we investigate how exogenous and endogenous orienting of spatial attention affect visuospatial working memory (VSWM). Specifically, we focused on two attentional effects and their consequences on storage in VSWM, when exogenous (Experiment 1) or endogenous (Experiment 2) orienting cues were used. The first effect, known as the meridian effect, is given by a decrement in behavioural performance when spatial cues and targets are presented in locations separated by vertical and/or horizontal meridians. The second effect, known as the distance effect, is given by a decrement in the orienting effects as a function of the spatial distance between cues and targets. Our results revealed a dissociation between exogenous and endogenous orienting mechanisms in terms of both meridian and distance effects. We found that meridian crossing affects performance only when endogenous cues were used. Specifically, VSWM performance with endogenous cueing depended more on the number of meridian crossings than on distance between cue and target. By contrast, a U-shaped distance dependency was observed using exogenous cues. Our findings therefore suggest that exogenous and endogenous orienting mechanisms lead to different forms of attentional bias for storage in VSWM.

  10. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2016-06-01

    Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

  11. The population history of endogenous retroviruses in mule deer (Odocoileus heminous)

    Science.gov (United States)

    Kamath, Pauline L.; Elleder, Daniel; Bao, Le; Cross, Paul C.; Powell, John H.; Poss, Mary

    2013-01-01

    Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5′ and 3′ long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations.

  12. The population history of endogenous retroviruses in mule deer (Odocoileus hemionus).

    Science.gov (United States)

    Kamath, Pauline L; Elleder, Daniel; Bao, Le; Cross, Paul C; Powell, John H; Poss, Mary

    2014-01-01

    Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5' and 3' long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations.

  13. Polymorphic integrations of an endogenous gammaretrovirus in the mule deer genome.

    Science.gov (United States)

    Elleder, Daniel; Kim, Oekyung; Padhi, Abinash; Bankert, Jason G; Simeonov, Ivan; Schuster, Stephan C; Wittekindt, Nicola E; Motameny, Susanne; Poss, Mary

    2012-03-01

    Endogenous retroviruses constitute a significant genomic fraction in all mammalian species. Typically they are evolutionarily old and fixed in the host species population. Here we report on a novel endogenous gammaretrovirus (CrERVγ; for cervid endogenous gammaretrovirus) in the mule deer (Odocoileus hemionus) that is insertionally polymorphic among individuals from the same geographical location, suggesting that it has a more recent evolutionary origin. Using PCR-based methods, we identified seven CrERVγ proviruses and demonstrated that they show various levels of insertional polymorphism in mule deer individuals. One CrERVγ provirus was detected in all mule deer sampled but was absent from white-tailed deer, indicating that this virus originally integrated after the split of the two species, which occurred approximately one million years ago. There are, on average, 100 CrERVγ copies in the mule deer genome based on quantitative PCR analysis. A CrERVγ provirus was sequenced and contained intact open reading frames (ORFs) for three virus genes. Transcripts were identified covering the entire provirus. CrERVγ forms a distinct branch of the gammaretrovirus phylogeny, with the closest relatives of CrERVγ being endogenous gammaretroviruses from sheep and pig. We demonstrated that white-tailed deer (Odocoileus virginianus) and elk (Cervus canadensis) DNA contain proviruses that are closely related to mule deer CrERVγ in a conserved region of pol; more distantly related sequences can be identified in the genome of another member of the Cervidae, the muntjac (Muntiacus muntjak). The discovery of a novel transcriptionally active and insertionally polymorphic retrovirus in mammals could provide a useful model system to study the dynamic interaction between the host genome and an invading retrovirus.

  14. Quantification of fumarate and investigation of endogenous and exogenous fumarate stability in rat plasma by LC-MS/MS.

    Science.gov (United States)

    Shi, Yao; Tse, Susanna; Rago, Brian; Yapa, Udeni; Li, Fumin; Fast, Douglas M

    2016-04-01

    Fumaric acid is a commonly used excipient in pharmaceutical products. It is not known if its presence may lead to fluctuation of endogenous fumarate levels. An LC-MS/MS method was developed and validated to quantify fumarate in support of a toxicokinetics study. Stability evaluation showed that endogenous fumarate was stable for 6 h at room temperature, while exogenously added fumaric acid was converted to malate within 1 h due to the presence of fumarase. Citric acid, a fumarase inhibitor, prevented the conversion of added fumaric acid in rat plasma. The method was validated in citric acid stabilized rat plasma using a surrogate matrix approach. A discrepancy in stability was observed between endogenous fumarate and exogenously added fumaric acid.

  15. Alpha Power Modulates Perception Independently of Endogenous Factors

    Directory of Open Access Journals (Sweden)

    Sasskia Brüers

    2018-04-01

    Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

  16. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

    1979-01-01

    Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

  17. An endogenous standard, radioisotopic ratio method in NAA

    International Nuclear Information System (INIS)

    Byrne, A.R.; Dermelj, M.

    1997-01-01

    A derivative form of NAA is proposed which is based on the use of an endogenous internal standard of already known concentration in the sample. If a comparator with a known ratio of the determinand and endogenous standard are co-irradiated with the sample, the determinand concentration is derived in terms of the endogenous standard concentration and the activity ratios of the two induced nuclides in the sample and comparator. As well as eliminating the sample mass and greatly reducing errors caused by pulse pile-up and geometrical differences, it was shown that in the radiochemical mode, if the endogenous standard is chosen so that the induced activity is radioisotopic with that from the determinand, the radiochemical yield is also eliminated and the risk non-achievement of isotopic exchange greatly reduced. The method is demonstrated with good results on reference materials for the determination of I, Mn and Ni. The advantages and disadvantages of this approach are discussed. It is suggested that it may be of application in quality control and in extending the range of certified elements in reference materials. (author)

  18. Novel endogenous angiogenesis inhibitors and their therapeutic potential.

    Science.gov (United States)

    Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

    2015-10-01

    Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

  19. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

  20. Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

    Science.gov (United States)

    Holl, Katsiaryna; Lundin, Eva; Surcel, Heljä-Marja; Grankvist, Kjell; Koskela, Pentti; Dillner, Joakim; Hallmans, Göran; Wadell, Göran; Olafsdottir, Gudridur H; Ogmundsdottir, Helga M; Pukkala, Eero; Lehtinen, Matti; Stattin, Pär; Lukanova, Annekatrin

    2009-06-15

    According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Copyright 2008 UICC.

  1. Possible association of norepinephrine transporter -3081(A/T polymorphism with methylphenidate response in attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Shin Min-Sup

    2010-10-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a heritable disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Methylphenidate (MPH has been shown to block the norepinephrine transporter (NET, and genetic investigations have demonstrated that the norepinephrine transporter gene (SLC6A2 is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 -3081(A/T and G1287A polymorphisms with MPH response in ADHD. Methods This study enrolled 112 children and adolescents with ADHD. A response criterion was defined based on the Clinical Global Impression-Improvement (CGI-I score, and the ADHD Rating Scale-IV (ARS score was also assessed at baseline and 8 weeks after MPH treatment. Results We found that the subjects who had the T allele as one of the alleles (A/T or T/T genotypes at the -3081(A/T polymorphism showed a better response to MPH treatment than those with the A/A genotype as measured by the CGI-I. We also found a trend towards a difference in the change of the total ARS scores and hyperactivity/impulsivity subscores between subjects with and without the T allele. No significant association was found between the genotypes of the SLC6A2 G1287A polymorphism and response to ADHD treatment. Conclusion Our findings provide evidence for the involvement of the -3081(A/T polymorphism of SLC6A2 in the modulation of the effectiveness of MPH treatment in ADHD.

  2. Synthesis and biological evaluation of trans-3-phenyl-1-indanamines as potential norepinephrine transporter imaging agents

    International Nuclear Information System (INIS)

    McConathy, Jonathan; Owens, Michael J.; Kilts, Clinton D.; Malveaux, Eugene J.; Votaw, John R.; Nemeroff, Charles B.; Goodman, Mark M.

    2005-01-01

    The development of radioligands suitable for studying the central nervous system (CNS) norepinephrine transporter (NET) in vivo will provide important new tools for examining the pathophysiology and pharmacotherapy of a variety of neuropsychiatric disorders including major depression. Towards this end, a series of trans-3-phenyl-1-indanamine derivatives were prepared and evaluated in vitro. The biological properties of the most promising compound, [ 11 C]3-BrPA, were investigated in rat biodistribution and nonhuman primate PET studies. Despite high in vitro affinity for the human NET, the uptake of [ 11 C]3-BrPA in the brain and the heart was not displaceable with pharmacological doses of NET antagonists

  3. Bulk derivatization and direct injection of human cerebrospinal fluid for trace-level quantification of endogenous estrogens using trap-and-elute liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Fan, Hui; Papouskova, Barbora; Lemr, Karel; Wigginton, Jane G; Schug, Kevin A

    2014-08-01

    Although there are existing methods for determining estrogen in human bodily fluids including blood plasma and serum, very little information is available regarding estrogen levels in human cerebrospinal fluid (CSF), which is critical to assess in studies of neuroprotective functions and diffusion of neuroprotective estrogens across the blood-brain barrier. To address this problem, a liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of four endogenous estrogens (estrone, 17α-estradiol, 17β-estradiol, and estriol) in human CSF was developed. An aliquot (300 μL) of human CSF was bulk derivatized using dansyl chloride in the sample and 10 μL was directly injected onto a restricted-access media trap column for protein removal. No off-line sample extraction or cleanup was needed. The limits of detection of estrone, 17α-estradiol, 17β-estradiol, and estriol were 17, 28, 13, and 30 pg/mL, respectively, which is in the parts-per-trillion regime. The method was then applied to human CSF collected from ischemic trauma patients. Endogenous estrogens were detected and quantified, demonstrating the effectiveness of this method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Demonstration of endogenous imipramine like material in rat brain

    International Nuclear Information System (INIS)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-01-01

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

  5. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2014-04-01

    Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Government technology push in agribusiness: a model of endogenous growth

    Directory of Open Access Journals (Sweden)

    Francisco Venegas Martínez

    2008-10-01

    Full Text Available This paper develops a model of endogenous growth where the government acts as a promoting agent to boost technology in agribusiness. In the framework of a monetary economy, the optimal level of government spending to enhance technology in the agricultural industry is characterized. Moreover the impact of such a spending on economic welfare is assessed. Finally, a number of agro-oriented policies to increase growth in the sector are established.

  7. Norepinephrine and dopamine increase motility, biofilm formation, and virulence of Vibrio harveyi.

    Science.gov (United States)

    Yang, Qian; Anh, Nguyen D Q; Bossier, Peter; Defoirdt, Tom

    2014-01-01

    Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine (NE) and dopamine (Dopa) increased growth in serum-supplemented medium, siderophore production, swimming motility, and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, NE-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopa-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesize that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host.

  8. Differences between endogenous and exogenous emotion inhibition in the human brain.

    Science.gov (United States)

    Kühn, Simone; Haggard, Patrick; Brass, Marcel

    2014-05-01

    The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

  9. Horizontalists, verticalists, and structuralists: The theory of endogenous money reassessed

    OpenAIRE

    Palley, Thomas I.

    2013-01-01

    This paper uses the occasion of the twenty-fifth anniversary of Basil Moore’s book, Horizontalists and Verticalists, to reassess the theory of endogenous money. The paper distinguishes between horizontalists, verticalists, and structuralists. It argues Moore’s horizontalist representation of endogenous money was an over-simplification that discarded important enduring insights from monetary theory. The structuralist approach to endogenous money retains the basic insight that the money supply ...

  10. Comparison of dynamic changes in endogenous hormone level, water content and water-soluble sugars in camellia oleifera of different ages

    International Nuclear Information System (INIS)

    Hu, J.; Shah, F.A.; Fu, S.; Wu, W.

    2017-01-01

    The aim of this study is to investigate and understand the dynamic changes and the possible functions of hormones, water and sugar content during the development of C. oleifera. We analyzed and compared WWC, WSS and five endogenous hormones (DHZR, ZR, GA, IAA and ABA) contents between May and August in C. oleifera plants at different ages from the same orchard. The results showed that WWC, WSS, DHZR, ZR, GA, IAA and ABA contents varied from 61.64%-74.15%, 21.24mg/g-62.44mg/g, 6.237ng/g-38.342ng/g, 6.215ng/g-16.721ng/g, 5.668ng/g-18.024ng/g, 24.753ng/g-147.507ng/g and 66.541ng/g-156.212ng/g, respectively. WWC showed a decrease-increase-decrease variation pattern, while the WSS contents demonstrated a generally increasing trend with increasing tree age. The levels of ABA in leaves sampled in August was higher than that in May, but the opposite was found for the GA and IAA levels. Tree ages were negatively correlated with ZR and GA concentration at the 1% or 5% significance level. The results of this study broaden our understanding of the interrelationships between phytohormones, WWC, and WSS content in the growth and development of C. oleifera. (author)

  11. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    International Nuclear Information System (INIS)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi

    2015-01-01

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H 2 S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H 2 S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H 2 S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H 2 S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H 2 S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H 2 S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions

  12. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

    2015-01-02

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.

  13. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  14. The endogenous bacteria alter gut epithelial apoptosis and decrease mortality following Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Fox, Amy C; McConnell, Kevin W; Yoseph, Benyam P; Breed, Elise; Liang, Zhe; Clark, Andrew T; O'Donnell, David; Zee-Cheng, Brendan; Jung, Enjae; Dominguez, Jessica A; Dunne, W Michael; Burd, Eileen M; Coopersmith, Craig M

    2012-11-01

    The endogenous bacteria have been hypothesized to play a significant role in the pathophysiology of critical illness, although their role in sepsis is poorly understood. The purpose of this study was to determine how commensal bacteria alter the host response to sepsis. Conventional and germ-free (GF) C57Bl/6 mice were subjected to Pseudomonas aeruginosa pneumonia. All GF mice died within 2 days, whereas 44% of conventional mice survived for 7 days (P = 0.001). Diluting the dose of bacteria 10-fold in GF mice led to similar survival in GF and conventional mice. When animals with similar mortality were assayed for intestinal integrity, GF mice had lower levels of intestinal epithelial apoptosis but similar levels of proliferation and intestinal permeability. Germ-free mice had significantly lower levels of tumor necrosis factor and interleukin 1β in bronchoalveolar lavage fluid compared with conventional mice without changes in systemic cytokine production. Under conventional conditions, sepsis unmasks lymphocyte control of intestinal epithelial apoptosis, because sepsis induces a greater increase in gut apoptosis in Rag-1 mice than in wild-type mice. However, in a separate set of experiments, gut apoptosis was similar between septic GF Rag-1 mice and septic GF wild-type mice. These data demonstrate that the endogenous bacteria play a protective role in mediating mortality from pneumonia-induced sepsis, potentially mediated through altered intestinal apoptosis and the local proinflammatory response. In addition, sepsis-induced lymphocyte-dependent increases in gut epithelial apoptosis appear to be mediated by the endogenous bacteria.

  15. Antimicrobial activity and mechanism of PDC213, an endogenous peptide from human milk

    International Nuclear Information System (INIS)

    Sun, Yazhou; Zhou, Yahui; Liu, Xiao; Zhang, Fan; Yan, Linping; Chen, Ling; Wang, Xing; Ruan, Hongjie; Ji, Chenbo; Cui, Xianwei; Wang, Jiaqin

    2017-01-01

    Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and disk diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation. - Highlights: • PDC213 is an endogenous peptide presenting higher levels in preterm milk. • PDC213 showed obvious antimicrobial against S. aereus and Y. enterocolitica. • PDC213 can permeabilize bacterial membranes and cell walls to kill bacterias. • PDC213 is a novel type of antimicrobial peptides worthy further investigation.

  16. Subcellular localization of the antidepressant-sensitive norepinephrine transporter

    Directory of Open Access Journals (Sweden)

    Winder Danny G

    2009-06-01

    Full Text Available Abstract Background Reuptake of synaptic norepinephrine (NE via the antidepressant-sensitive NE transporter (NET supports efficient noradrenergic signaling and presynaptic NE homeostasis. Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons. Results We elucidate NET localization in brain and superior cervical ganglion (SCG neurons, aided by a new NET monoclonal antibody, subcellular immunoisolation techniques and quantitative immunofluorescence approaches. We present evidence that axonal NET extensively colocalizes with syntaxin 1A, and to a limited degree with SCAMP2 and synaptophysin. Intracellular NET in SCG axons and boutons also quantitatively segregates from the vesicular monoamine transporter 2 (VMAT2, findings corroborated by organelle isolation studies. At the surface of SCG boutons, NET resides in both lipid raft and non-lipid raft subdomains and colocalizes with syntaxin 1A. Conclusion Our findings support the hypothesis that SCG NET is segregated prior to transport from the cell body from proteins comprising large dense core vesicles. Once localized to presynaptic boutons, NET does not recycle via VMAT2-positive, small dense core vesicles. Finally, once NET reaches presynaptic plasma membranes, the transporter localizes to syntaxin 1A-rich plasma membrane domains, with a portion found in cholera toxin-demarcated lipid rafts. Our findings indicate that activity-dependent insertion of NET into the SCG plasma membrane derives from vesicles distinct from those that deliver NE. Moreover, NET is localized in presynaptic membranes in a manner that can take advantage of regulatory processes targeting lipid raft subdomains.

  17. Exogenic and endogenic Europa minerals

    Science.gov (United States)

    Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

    2016-12-01

    The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

  18. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  19. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

  20. Effect of endogenous biotin on the applications of streptavidin and biotin in mice

    International Nuclear Information System (INIS)

    Rusckowski, Mary; Fogarasi, Miklos; Fritz, Benjamin; Hnatowich, Donald J.

    1997-01-01

    The use of streptavidin-conjugated antibody to pretarget tumors in animals and patients, prior to administration of radiolabeled biotin, has provided encouraging results, in part because of the high affinity of biotin for streptavidin and the rapid whole-body clearance of biotin. However, binding of endogenous biotin to streptavidin may interfere with the clinical potential of this approach. This report evaluates the effect of endogenous biotin on an antibody-streptavidin conjugate in a mouse tumor model. Tumored nude mice were depleted of endogenous biotin by sequential intraperitoneal injections of streptavidin. The assay of serum biotin levels indicated less than 0.5 ng of biotin per mL of serum in treated mice versus 4 ng per mL in untreated animals. Flow cytometric analysis was used on single-cell suspensions of tumor from animals receiving streptavidin-conjugated IgG to detect the presence of the antibody on the cell membrane (with fluoroisothiocyanate-conjugated goat anti-mouse antibody), and to detect biotin binding sites on streptavidin (with biotin-phycoerythrin). Both treated and untreated mice demonstrated the presence of antibody on tumor cells through 48 h postadministration, but only in treated animals were biotin binding sites observed. These results in the mouse model suggest that the small concentration of streptavidin delivered to a tumor via a specific antibody may be saturated with endogenous biotin and therefore not able to be targeted subsequently with radiolabeled biotin

  1. Study of mango endogenous pectinases as a tool to engineer mango purée consistency.

    Science.gov (United States)

    Jamsazzadeh Kermani, Zahra; Shpigelman, Avi; Houben, Ken; ten Geuzendam, Belinda; Van Loey, Ann M; Hendrickx, Marc E

    2015-04-01

    The objective of this work was to evaluate the possibility of using mango endogenous pectinases to change the viscosity of mango purée. Hereto, the structure of pectic polysaccharide and the presence of sufficiently active endogenous enzymes of ripe mango were determined. Pectin of mango flesh had a high molecular weight and was highly methoxylated. Pectin methylesterase showed a negligible activity which is related to the confirmed presence of a pectin methylesterase inhibitor. Pectin contained relatively high amounts of galactose and considerable β-galactosidase (β-Gal) activity was observed. The possibility of stimulating β-Gal activity during processing (temperature/pressure, time) was investigated. β-Gal of mango was rather temperature labile but pressure stable relatively to the temperature and pressure levels used to inactivate destructive enzymes in industry. Creating processing conditions allowing endogenous β-Gal activity did not substantially change the consistency of mango purée. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Some observations about the endogenous money theory

    OpenAIRE

    Bertocco Giancarlo

    2006-01-01

    The endogenous money theory constitutes the core element of the post-keynesian monetary theory. The first formulation of this theory can be found in the works of Kaldor published in the 1970s. Taking these studies as a starting point, the post-keynesians elaborated two versions of the endogenous money theory which differ in their assumptions about the behaviour of the monetary authorities and the banking system, and hence offer different conclusions about the slope of the money supply curve. ...

  3. CITROBACTER ENDOGENOUS ENDOPHTHALMITIS: A CASE REPORT AND REVIEW OF THE LITERATURE.

    Science.gov (United States)

    Wong, Daniel H T; Liu, Candice C H; Tong, Justin M K; Luk, Wei-Kwang; Li, Kenneth K W

    2017-11-16

    We present a case of endogenous endophthalmitis because of an unusual bacterium, Citrobacter koseri. A 57-year-old woman without previous history of eye surgery or trauma presented with diabetic ketoacidosis and a painful right eye with the reduction of vision. C. koseri was identified in blood culture; thus, a diagnosis of right eye endogenous endophthalmitis was made. Intravenous and intravitreal antibiotics were both started, and vitreous culture further confirmed C. koseri as the causative organism. Computed tomography of the abdomen and pelvis revealed a right C-shaped perinephric abscess, which was drained under ultrasound guidance. Because of rapid progression to corneal melting, evisceration was performed. Cases of endogenous endophthalmitis caused by Citrobacter are very limited, and a review of all published cases in the English literature and the present case revealed that endogenous Citrobacter endophthalmitis arose almost entirely from Citrobacter renal infection. Early recognition and drainage of renal abscess may lower the chance of uncontrolled infection and endogenous spread to the eyes. Despite prompt and intensive treatment, the clinical outcome of Citrobacter endogenous endophthalmitis seems to be poor.

  4. Strategies for the photo-control of endogenous protein activity.

    Science.gov (United States)

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2017-08-01

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Endogenous lung regeneration: potential and limitations.

    Science.gov (United States)

    Rock, Jason; Königshoff, Melanie

    2012-12-15

    The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.

  6. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  7. Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

    Science.gov (United States)

    Steeples, L R; Jones, N P

    2016-01-01

    PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

  8. [Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

    Science.gov (United States)

    Robaczyk, Maciej G

    2002-01-01

    The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk

  9. Assessment the effect of NO inhibition on hippocampal normetanephrine level in stress and non-stress conditions in adult male rats

    Directory of Open Access Journals (Sweden)

    Hana Molahoveizeh

    2016-01-01

    Full Text Available Background: Nitric oxide (NO has a role in the regulation of neurotransmitters release such as norepinephrine, in the hippocampus.Normetanephrine (NMN is a metabolite of norepinephrine created by action of catechol-O-methyl transferase (COMT on norepinephrine. Several studies have shown that various stresses increased release of norepinephrine and its metabolites. Therefore in the present study, the role of Nitric oxide in regulation of norepinephrine release and its metabolism was investigated by administration of L-NAME (NO synthase inhibitor in stressed and non-stressed rats. Materials and Methods: For this purpose, 50 adult rats were divided into 10 groups, of which 5 groups were exposed to restraint stress while another 5 groups were without stress. These two set of groups included intact, saline and L-NAME (20, 40, 80 mg/kg. Thirty minutes after intraperituneal injection of L-NAME, brains removed, the hippocampus dissected, weighed, homogenized and centrifuged then amount of NMN measured by ELISA kit. Results: The results showed that in non-stressed condition amount of NMN were significantly increased in group that received L-NAME (80 mg/kg in comparison with other groups but in stress condition, amount of NMN was significantly decreased in groups that received L-NAME (20,40,80 mg/kg, in comparison with control and saline groups. Comparison between stress and non-stressed groups showed that stress alone cause an increase in amount of NMN in control and saline groups. Conclusion: In conclusion, NO synthesis inhibition produced opposite responses with respect to NMN amount in the presence or absence of stress, and probably L-NAME preventing the effect of stress on increasing NMN levels mediated by nitrergic pathway.

  10. Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance

    Science.gov (United States)

    Martino, Matteo; Rocchi, Giulio; Escelsior, Andrea; Fornaro, Michele

    2012-01-01

    Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies. PMID:23204981

  11. The epigenetic alterations of endogenous retroelements in aging.

    Science.gov (United States)

    Cardelli, Maurizio

    2018-02-16

    Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Expression and function of endogenous retroviruses in the placenta.

    Science.gov (United States)

    Denner, Joachim

    2016-01-01

    Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  13. School system evaluation by value added analysis under endogeneity.

    Science.gov (United States)

    Manzi, Jorge; San Martín, Ernesto; Van Bellegem, Sébastien

    2014-01-01

    Value added is a common tool in educational research on effectiveness. It is often modeled as a (prediction of a) random effect in a specific hierarchical linear model. This paper shows that this modeling strategy is not valid when endogeneity is present. Endogeneity stems, for instance, from a correlation between the random effect in the hierarchical model and some of its covariates. This paper shows that this phenomenon is far from exceptional and can even be a generic problem when the covariates contain the prior score attainments, a typical situation in value added modeling. Starting from a general, model-free definition of value added, the paper derives an explicit expression of the value added in an endogeneous hierarchical linear Gaussian model. Inference on value added is proposed using an instrumental variable approach. The impact of endogeneity on the value added and the estimated value added is calculated accurately. This is also illustrated on a large data set of individual scores of about 200,000 students in Chile.

  14. Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification.

    Science.gov (United States)

    Malliaras, Konstantinos; Vakrou, Styliani; Kapelios, Chris J; Nanas, John N

    2016-11-01

    The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

  15. Effect of the alkaloid (-)cathinone on the release of radioactivity from rabbit atria prelabelled with 3H-norepinephrine

    International Nuclear Information System (INIS)

    Kalix, P.

    1983-01-01

    In certain countries of East Africa and the Arab Peninsula, fresh leaves of the khat shrub are used as a stimulant. The effect of the plant material can be explained by the presence of the phenylalklamine alkaloid (-)cathinone in the leaves, since this substance has been shown to have an amphetamine-like releasing effect on CNS tissue prelabelled with 3 H-dopamine. Characteristically, the chewing of khat is accompanied by sympathomimetic effects, especially at the cardiovascular level. To test whether these might be due to release of neurotransmitter from adrenergic nerve endings, the effect of (-)cathinone on the efflux of radioactivity from isolated rabbit atrium tissue prelabelled with 3 H-norepinephrine was investigated. It was found that, at concentrations below 1 μM, (-)cathinone caused an immediate increase of efflux. The effect was dose-dependent and was potentiated by pretreatment of the rabbits with reserpine. Preincubation of the tissue with desipramine and cocaine prevented the induction of release by (-)cathinone. The results indicate that the alkaloid (-)cathinone has an amphetamine-like releasing effect on noradrenergic nerve endings and they suggest that the cardiovascular symptoms observed during khat consumption are due to release of neurotransmitter from physiologicl storage sites

  16. Ethanol extract of Portulaca oleracea L. protects against hypoxia-induced neuro damage through modulating endogenous erythropoietin expression.

    Science.gov (United States)

    Wanyin, Wang; Liwei, Dong; Lin, Jia; Hailiang, Xin; Changquan, Ling; Min, Li

    2012-04-01

    In addition to its role in erythropoiesis, erythropoietin is also appreciated for its neuroprotective effects, and it has been suggested for treatment of some ischemic-hypoxic neurovascular diseases. The protective effects of endogenous erythropoietin in the brain give rise to the hypothesis that modulating erythropoietin expression might be a better way for treatment of ischemia-hypoxia neurovascular diseases. We have found that ethanol extract of Portulaca oleracea L. (EEPO) could increase erythropoietin expression in hypoxic mouse brain in our previous study. The present study is to investigate whether EEPO exerts its neuroprotective effects against hypoxia injury through regulating endogenous erythropoietin expression. The results demonstrated that EEPO decreased the serum neuron specific enolase level in hypoxia mice and the activity of caspase-3 in neuron, increased the neuron viability and attenuated the pathological damages caused by the hypoxia condition. Importantly, we also found that EEPO stimulated the endogenous erythropoietin expression at both mRNA and protein levels. Using the conditioned medium containing soluble erythropoietin receptor, we found that the neuroprotective effects of EEPO were dependent, at least partly, on erythropoietin expression. Although EEPO did not affect transcription of hypoxia inducible factor-1α (HIF-1α), it did stabilize expression of HIF-1α. It is concluded that EEPO has neuroprotective effects against hypoxia injury, which is at least partly through stimulating endogenous erythropoietin expression by stabilizing HIF-1α. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Differential diagnosis algorithm of endogenous catatonia, catatonia-morphic and catatonia-mimicking states

    Directory of Open Access Journals (Sweden)

    D. N. Safonov

    2017-08-01

    Full Text Available Subject relevance. The process of mental pathology pathomorphosis leads to the polymorphism of its clinical manifestations and, as a consequence – to difficulties in identification and differential diagnosis. The solution to this problem is in the adaption of diagnostic methodology to clinical realities by including into their structure instruments formed basing on pathomorphosis factors and trends. In this perspective, the most prominent example is endogenous catatonia, which in the academic tradition is conventionally affiliated with the form of schizophrenia with the same name. According to the classical understanding, endogenous catatonia, or, in the narrow sense – catatonic syndrome, is a group of intermittent motor disorders, arranged with polymorphic shell constellation of neuropsychiatric manifestations. The aim is to develop pathomorphosis adapted clinical algorithm of endogenous catatonia differential diagnostics. Materials and methods: 236 patients of Zaporizhzhia Regional Psychiatric Clinic were examined. Patients were divided into groups due to their mental disorders: – core group: patients with elements of endogenous catatonia in the structure of different clinical forms of schizophrenia (there were 144 patients in this group; – comparison group #1: 69 patients with late neurotropic effects of neuroleptic therapy (LNENT; – comparison group #2: 103 patients with catatonia-morphic dissociative disorders (CDD; – comparison group #3: 90 patients with organic catatonic disorder (OrCD; Results. Using Bush-Francis Catatonia Rating scale as an instrument of clinical analysis and statistical research of results with A. Wald’s sequential analysis (modificated by E. V. Gubler an algorithm of differential diagnostics of endogenus catatonia which includes 3 steps of Recognition Scale for Endogenous Catatonia is developed. Conclusion. Designed scales have a number of categorical differences from existing analogues, foremost by

  18. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism.

    Science.gov (United States)

    Eltzschig, Holger K; Thompson, Linda F; Karhausen, Jorn; Cotta, Richard J; Ibla, Juan C; Robson, Simon C; Colgan, Sean P

    2004-12-15

    Hypoxia is a well-documented inflammatory stimulus and results in tissue polymorphonuclear leukocyte (PMN) accumulation. Likewise, increased tissue adenosine levels are commonly associated with hypoxia, and given the anti-inflammatory properties of adenosine, we hypothesized that adenosine production via adenine nucleotide metabolism at the vascular surface triggers an endogenous anti-inflammatory response during hypoxia. Initial in vitro studies indicated that endogenously generated adenosine, through activation of PMN adenosine A(2A) and A(2B) receptors, functions as an antiadhesive signal for PMN binding to microvascular endothelia. Intravascular nucleotides released by inflammatory cells undergo phosphohydrolysis via hypoxia-induced CD39 ectoapyrase (CD39 converts adenosine triphosphate/adenosine diphosphate [ATP/ADP] to adenosine monophosphate [AMP]) and CD73 ecto-5'-nucleotidase (CD73 converts AMP to adenosine). Extensions of our in vitro findings using cd39- and cd73-null animals revealed that extracellular adenosine produced through adenine nucleotide metabolism during hypoxia is a potent anti-inflammatory signal for PMNs in vivo. These findings identify CD39 and CD73 as critical control points for endogenous adenosine generation and implicate this pathway as an innate mechanism to attenuate excessive tissue PMN accumulation.

  19. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  20. Social Laughter Triggers Endogenous Opioid Release in Humans.

    Science.gov (United States)

    Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

    2017-06-21

    The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

  1. Endogenous induced technical change and the costs of Kyoto

    International Nuclear Information System (INIS)

    Buonanno, Paolo; Carraro, Carlo; Galeotti, M.

    2001-09-01

    Many predictions and conclusions in the climate change literature have been made and drawn on the basis of theoretical analyses and quantitative models that are either static or that allow for simple forms of changes in technology, often along exogenously given time paths. It is therefore not clear a priori whether those conclusions and policy recipes still hold in the more realistic case of endogenously evolving technologies. In this paper, a quantitative tool with the features of an endogenous growth model is presented, which also accounts for the possibility that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon the stock of knowledge, which accumulates through R and D activities. R and D is thus an additional policy variable that comes into play along with pollution abatement and capital investment. Two versions of this climate model are studied, one with endogenous technical change but exogenous environmental technical change (i.e. no induced technical change) and the other with both endogenous and induced technical change. Hence, in both models technical change evolves endogenously as far as the production technology is concerned, but endogenous environmental (or induced) technical change is only accounted for in the second version. Finally, a third version of the model also captures technological spillover effects. As an application, the three versions of the model are simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

  2. Impact of cell culture process changes on endogenous retrovirus expression.

    Science.gov (United States)

    Brorson, Kurt; De Wit, Christina; Hamilton, Elizabeth; Mustafa, Mehnaz; Swann, Patrick G; Kiss, Robert; Taticek, Ron; Polastri, Gian; Stein, Kathryn E; Xu, Yuan

    2002-11-05

    Cell culture process changes (e.g., changes in scale, medium formulation, operational conditions) and cell line changes are common during the development life cycle of a therapeutic protein. To ensure that the impact of such process changes on product quality and safety is minimal, it is standard practice to compare critical product quality and safety attributes before and after the changes. One potential concern introduced by cell culture process improvements is the possibility of increased endogenous retrovirus expression to a level above the clearance capability of the subsequent purification process. To address this, retrovirus expression was measured in scaled down and full production scaled Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one recombinant protein before and after process changes. Two highly sensitive, quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses. It is shown that cell culture process changes that primarily alter media components, nutrient feed volume, seed density, cell bank source (i.e., master cell bank vs. working cell bank), and vial size, or culture scale, singly or in combination, do not impact the rate of retrovirus expression to an extent greater than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes that significantly alter the metabolic state of the cells and/or rates of protein expression (e.g., pH and temperature shifts, NaButyrate addition) measurably impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of variation in endogenous retrovirus expression was observed between individual cell lines (up to 3 log(10)). These data support the practice of measuring endogenous retrovirus output for each new cell line introduced into manufacturing or after process changes that significantly increase product-specific productivity or alter the metabolic state, but suggest that reassessment of retrovirus expression after other

  3. A panel Granger-causality test of endogenous vs. exogenous growth

    OpenAIRE

    Jochen Hartwig

    2009-01-01

    The paper proposes a new test of endogenous vs. exogenous growth theories based on the Granger-causality methodology and applies it to a panel of 20 OECD countries. The test yields divergent evidence with respect to physical and human capital. For physical capital, the test results favor Solow-type exogenous growth theory over AK-type endogenous growth models. On the other hand, the test results lend support to human capital oriented endogenous growth models - like the Uzawa-Lucas model - rat...

  4. Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

    Science.gov (United States)

    Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

    2018-03-30

    Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle

  5. Endogenous immunoreactive digitalis-like substance in neonatal serum and placental extracts

    International Nuclear Information System (INIS)

    Beyers, A.D.; Spruyt, L.L.; Seifart, H.I.; Kriegler, A.; Parkin, D.P.; Van Jaarsveld, P.P.

    1984-01-01

    Therapeutic levels of digoxin in the serum of untreated neonates delivered to mothers who had not received the drug prenatally were detected by radio-immunoassay. Digoxin levels in neonates should be interpreted with care because of the unknown contribution by the endogenous digitalis-like substance (DLS) to the level of the drug. Three commercially available radio-immunoassay kits were compared with regard to their sensitivity and reproducibility in detecting the endogenous DLS. The kit from Clinical Assays (Cambridge, Mass. USA) was selected for further investigations. In a series of 35 paired samples of maternal and cord blood the average DLS values in terms of digoxin were 0,52 plus minus 0,07 and 0,81 plus minus 0,27 ng/ml respectively. The difference is statistically highly significant. In the case of infants with DLS values of 1 - 1,5 ng/ml in terms of digoxin, approximately 1 week was required to reach non-therapeutic digoxin levels, i.e. below 0,5 ng/ml. Gel chromatography showed that the DLS in neonatal serum was more closely associated with protein than is authentic digoxin. In placental extracts it followed the elution profile of the protein completely, but it shifted to fractions with a lower molecular weight than haemoglobin after trypsinization. The level of DLS in neonatal serum was also increased by more than half its original value by trypsinization. Proteolysis therefore seems to have a releasing effect on DLS. The molecular size of this substance is probably in the same range as that of polypeptides, since it was not dialysable from trypsinized and untreated samples through a membrane with a 22 000 dalton molecular weight cut-off point

  6. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    International Nuclear Information System (INIS)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

    1986-01-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

  7. On the Endogeneity of the Mean-Variance Efficient Frontier.

    Science.gov (United States)

    Somerville, R. A.; O'Connell, Paul G. J.

    2002-01-01

    Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

  8. Endogenous Pain Modulation: Association with Resting Heart Rate Variability and Negative Affectivity.

    Science.gov (United States)

    Van Den Houte, Maaike; Van Oudenhove, Lukas; Bogaerts, Katleen; Van Diest, Ilse; Van den Bergh, Omer

    2017-07-21

    Several chronic pain syndromes are characterized by deficient endogenous pain modulation as well as elevated negative affectivity and reduced resting heart rate variability. In order to elucidate the relationships between these characteristics, we investigated whether negative affectivity and heart rate variability are associated with endogenous pain modulation in a healthy population. An offset analgesia paradigm with noxious thermal stimulation calibrated to the individual's pain threshold was used to measure endogenous pain modulation magnitude in 63 healthy individuals. Pain ratings during constant noxious heat stimulation to the arm (15 seconds) were compared with ratings during noxious stimulation comprising a 1 °C rise and return of temperature to the initial level (offset trials, 15 seconds). Offset analgesia was defined as the reduction in pain following the 1 °C decrease relative to pain at the same time point during continuous heat stimulation. Evidence for an offset analgesia effect could only be found when noxious stimulation intensity (and, hence, the individual's pain threshold) was intermediate (46 °C or 47 °C). Offset analgesia magnitude was also moderated by resting heart rate variability: a small but significant offset effect was found in participants with high but not low heart rate variability. Negative affectivity was not related to offset analgesia magnitude. These results indicate that resting heart rate variability (HRV) is related to endogenous pain modulation (EPM) in a healthy population. Future research should focus on clarifying the causal relationship between HRV and EPM and chronic pain by using longitudinal study designs. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter and α2 Adrenergic Receptor in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Qianli Tang

    2016-01-01

    Full Text Available To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter and α2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, and α2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET and α2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels of α2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

  10. Revelation of endogenously bound Fe{sup 2+} ions in the crystal structure of ferritin from Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Thiruselvam, Viswanathan [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India); Sivaraman, Padavattan [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kumarevel, Thirumananseri, E-mail: kumarevel.thirumananseri@riken.jp [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Structural Biology Laboratory, RIKEN Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Ponnuswamy, Mondikalipudur Nanjappagounder, E-mail: mnpsy2004@yahoo.com [Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025 (India)

    2014-10-24

    Highlights: • Crystal structure of ferritin was determined. • Endogenously expressed iron’s were identified. • Binuclear iron sites were observed at A and B active sites. - Abstract: Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5 Å. The structural analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.

  11. Effects of Aroclor 1254 on dopamine and norepinephrine concentrations in pheochromocytoma (PC-12) cells

    International Nuclear Information System (INIS)

    Seegal, R.F.; Brosch, K.; Bush, B.; Ritz, M.; Shain, W.

    1990-01-01

    Pheochromocytoma (PC-12) cells synthesize, store, release and metabolize dopamine (DA) and norepinephrine (NE) in a manner analogous to that observed in the mammalian central nervous system. These cells were used to develop and validate an alternate method to animal testing to assess the effects of a complex environmental mixture of polychlorinated biphenyls (Aroclor 1254) on cellular catecholamine function. Aroclor 1254, at concentrations of 1 to 100 ppm, significantly decreased cellular catecholamine concentrations after 6 hrs. Exposure at 100 ppm for periods of less than an hr increased cellular catecholamine concentrations while longer exposure times (i.e., 1 to 24 hr) decreased cellular catecholamine concentrations. This in vitro depletion of catecholamines is similar to that seen in vivo. Thus, PC-12 cells may be useful for neurochemical evaluation of neurotoxicants with particular reference to effects on catecholaminergic systems

  12. Effects of cadmium on the uptake of dopamine and norepinephrine in rat brain synaptosomes

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    Cadmium (Cd) a known environmental contaminant is neurotoxic. Kinetics of cadmium inhibition indicate that the metal may compete with ATP and Na + sites on Na + -K + ATPase in rat brain synaptosomes. Uptake and release processes of catecholamines into the central nervous system are dependent on membrane bound Na + -K + ATPase. It is suggested that the uptake and release processes of dopamine (DA) and norepinephrine (NE) in neurons are energy utilizing and hence are dependent on active ion transport. If the two aforementioned mechanisms are truly interdependent, then any alteration caused by a toxin to either of the above two mechanisms should also cause a parallel change in the other. The purpose of this study was to examine in vitro effects of cadmium chloride on the uptake of DA and NE and the activity of ATPase in the rat brain synaptosome

  13. Biopsychosocial Factors Associated with Prurigo Nodularis in Endogenous Eczema.

    Science.gov (United States)

    Oh, Choon Chiat; Li, Huihua; Lee, Wellington; Tey, Hong Liang

    2015-01-01

    Prurigo nodularis is a dermatological manifestation secondary to chronic scratching or picking on focal areas of the skin. Its pathogenesis remains poorly understood, and limited data has indicated its association with psychological factors. To determine the biological, psychological and social factors associated with the occurrence of prurigo nodularis in patients with underlying endogenous eczema. A prospective case-control questionnaire -based study on patients with endogenous eczema, with and without prurigo nodules, was performed. The Impact of Skin Disease on Daily Life questionnaire was used to assess dimensions of physical functioning, including extent and severity of skin disease, itch, pain, fatigue and scratching, as well as dimensions of psychological and social functioning, including mood, illness cognition, disease-related impact, stigmatization and social support. Thirty-six cases and 47 controls were recruited. Patients with endogenous eczema and prurigo nodules indicated a higher itch score on the visual analog scale over the previous 4 weeks compared to those without prurigo nodules (p=0.0292). There were no significant differences between the 2 groups in the scores reflecting the other parameters of physical, psychological and social functioning. In patients with endogenous eczema, those with prurigo nodules experience a greater itch intensity compared to those without prurigo nodules. There were no other physical, psychological and social factors that were found to be associated with the occurrence of prurigo nodules in endogenous eczema.

  14. Testing R&D-Based Endogenous Growth Models

    DEFF Research Database (Denmark)

    Kruse-Andersen, Peter Kjær

    2017-01-01

    R&D-based growth models are tested using US data for the period 1953-2014. A general growth model is developed which nests the model varieties of interest. The model implies a cointegrating relationship between multifactor productivity, research intensity, and employment. This relationship...... is estimated using cointegrated VAR models. The results provide evidence against the widely used fully endogenous variety and in favor of the semi-endogenous variety. Forecasts based on the empirical estimates suggest that the slowdown in US productivity growth will continue. Particularly, the annual long...

  15. Modification of sympathetic neuronal function in the rat tail artery by dietary lipid treatment

    International Nuclear Information System (INIS)

    Panek, R.L.; Dixon, W.R.; Rutledge, C.O.

    1985-01-01

    The effect of dietary lipid treatment on sympathetic neuronal function was examined in isolated perfused tail arteries of adult rats. The hypothesis that dietary manipulations alter the lipid environment of receptor proteins which may result in the perturbation of specific membrane-associated processes that regulate peripheral adrenergic neurotransmission in the vasculature was the basis for this investigation. In the present study, rats were fed semisynthetic diets enriched in either 16% coconut oil (saturated fat) or 16% sunflower oil (unsaturated fat). The field stimulation-evoked release of endogenous norepinephrine and total 3 H was decreased significantly in rats receiving the coconut oil diet when compared to either sunflower oil- or standard lab chow-fed rats. Norepinephrine content in artery segments from coconut oil-treated rats was significantly higher compared to either sunflower oil- or standard lab chow-fed rats. Tail arteries from rats receiving the coconut oil diet displayed significantly lower perfusion pressure responses to nerve stimulation at all frequencies tested when compared to the sunflower oil- or standard lab chow-fed rats. Vasoconstrictor responses of perfused tail arteries exposed to exogenous norepinephrine resulted in an EC50 for norepinephrine that was not changed by the dietary treatment, but adult rats receiving the sunflower oil diet displayed a significantly greater maximum response to exogenous norepinephrine (10(-5) M) compared to arteries from either coconut oil- or standard lab chow-fed rats

  16. The effect of pertussis toxin (PTX) treatment on blood pressure (BP), norepinephrine pressor responsiveness and BP response to acute nifedipine administration in genetic hypertension

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 48, č. 4 (2006), s. 773-774 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : pertussis toxin * blood pressure * norepinephrine * nifedipine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  17. Uniconazole-induced starch accumulation in the bioenergy crop duckweed (Landoltia punctata) I: transcriptome analysis of the effects of uniconazole on chlorophyll and endogenous hormone biosynthesis.

    Science.gov (United States)

    Liu, Yang; Fang, Yang; Huang, Mengjun; Jin, Yanling; Sun, Jiaolong; Tao, Xiang; Zhang, Guohua; He, Kaize; Zhao, Yun; Zhao, Hai

    2015-01-01

    Duckweed is a novel aquatic bioenergy crop that is found ubiquitously throughout the world. Uniconazole plays an important role in improving crop production through the regulation of endogenous hormone levels. We found that a high quantity and quality of duckweed growth can be achieved by uniconazole application, although the mechanisms are unknown. The fronds of Landoltia punctata were sprayed evenly with 800 mg/L uniconazole. The dry weight following treatment increased by 10% compared to the controls at 240 h. Endogenous cytokinin (CK) and abscisic acid (ABA) content both increased compared to the control, while the level of gibberellins (GAs) decreased. Additionally, gene expression profiling results showed that the expression of transcripts encoding key enzymes involved in endogenous CK and ABA biosynthesis were up-regulated, while the transcripts of key enzymes for GAs biosynthesis were down-regulated. On the other hand, chlorophyll a and chlorophyll b contents were both increased compared with the control. Moreover, the net photosynthetic rate was elevated to 25.6 μmol CO2/m(2)/s compared with the control value of 22.05 μmol CO2/m(2)/s. Importantly, the expression of some chlorophyll biosynthesis-related transcripts was up-regulated. Uniconazole treatment altered endogenous hormone levels and enhanced chlorophyll content and net photosynthetic rate in duckweed by regulating key enzymes involved in endogenous hormone and chlorophyll biosynthesis. The alterations of endogenous hormones and the increase of chlorophyll and photosynthetic rate data support the increase of biomass and starch accumulation.

  18. Financial constraints and international trade with endogenous mode of competition:

    OpenAIRE

    Bouët, Antoine; Vaubourg, Anne-Gaël

    2015-01-01

    The goal of this paper is to examine how financial constraints affect firms’ decisions to export when the mode of intra-sectoral competition is endogenous. We propose an extension of Neary and Tharakan’s (2012) model, in which firms resort to external funders to finance fixed export costs and investments in production capacities. We assume that sectors differ in financial constraint and that the cost of capital increases with the level of financial constraint. We first show that less financia...

  19. Norepinephrine metabolism in humans. Kinetic analysis and model

    International Nuclear Information System (INIS)

    Linares, O.A.; Jacquez, J.A.; Zech, L.A.; Smith, M.J.; Sanfield, J.A.; Morrow, L.A.; Rosen, S.G.; Halter, J.B.

    1987-01-01

    The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steady-state NE specific activity in arterialized plasma during [ 3 H]NE infusion and postinfusion plasma disappearance of [ 3 H]NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [ 3 H]NE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P less than 0.01) and upright (r = 0.90-0.98, all P less than 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87 +/- 0.08 vs. 3.25 +/- 0.2 micrograms/min per m2, P less than 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5 +/- 0.6 vs. 4.7 +/- 0.3 liters, P less than 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80 +/- 0.11 vs. 1.21 +/- 0.08 liters/min per m2, P less than 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans

  20. DMPD: Macrophage activation by endogenous danger signals. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18161744 Macrophage activation by endogenous danger signals. Zhang X, Mosser DM. J ...Pathol. 2008 Jan;214(2):161-78. (.png) (.svg) (.html) (.csml) Show Macrophage activation by endogenous dange...r signals. PubmedID 18161744 Title Macrophage activation by endogenous danger signals. Authors Zhang X, Moss

  1. Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: plasma norepinephrine concentration, hepatic extraction, and renal release

    DEFF Research Database (Denmark)

    Ring-Larsen, H; Hesse, B; Henriksen, Jens Henrik Sahl

    1982-01-01

    as previously reported in healthy controls. The right kidney released NE into the systemic circulation. Renal venous plasma NE exceeded arterial concentration by 34% (p less than 0.01). It is concluded that sympathetic nervous activity is enhanced in patients with cirrhosis, and that this hyperactivity may...... in patients than controls (82 vs. 95 mm Hg, p less than 0.05) but did not change during the tilt. Plasma norepinephrine (NE) concentration was significantly higher in another eight patients with cirrhosis than in eight healthy controls (mean: 0.45 vs. 0.21 ng per ml in recumbency, p less than 0.02). Following...

  2. A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain*

    Science.gov (United States)

    Scruggs, Sarah B.; Reisdorph, Rick; Armstrong, Mike L.; Warren, Chad M.; Reisdorph, Nichole; Solaro, R. John; Buttrick, Peter M.

    2010-01-01

    The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were

  3. Spatial orienting around the fovea: exogenous and endogenous cueing effects.

    Science.gov (United States)

    Yang, Taoxi; Zhang, Jiyuan; Bao, Yan

    2015-09-01

    The effect of covert attention in perifoveal and peripheral locations has been studied extensively. However, it is less clear whether attention operates similarly in the foveal area itself. The present study aims to investigate whether the attentional orienting elicited by an exogenous or endogenous cue can operate within the foveal area and whether attentional orienting operates similarly between foveal and perifoveal regions. By manipulating exogenous orienting in Experiment 1 and endogenous orienting in Experiment 2, we observed both forms of cueing in the foveal area. Specifically, we observed a larger exogenous cue-induced inhibitory effect (i.e., inhibition of return effect) and a similar endogenous cue-elicited facilitatory effect for the perifoveal relative to the foveal targets. We conclude that exogenous and endogenous orienting subject to two independent attentional systems with distinct modulation patterns in the foveal area.

  4. Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.

    Science.gov (United States)

    Tikhonenko, A T; Lomovskaya, O L

    1990-02-01

    The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome, as shown by oligonucleotide mapping. However, since the complete env gene sequence was not known, the comparison of genomic nucleotide sequences was not possible. Therefore an avian endogenous provirus with an intact env gene was cloned from a chicken gene bank and the regions coding for the C terminus of the gp85 and gp37 proteins were sequenced. Comparison of this sequence with those of other retroviruses proved that one of the pathogenic viruses associated with osteopetrosis is a cross between avian endogenous virus and Rous sarcoma virus. Retroviruses and, especially, endogenous retroviruses are traditionally of the most developed models of viral carcinogenesis. Many endogenous retroviruses are implicated in neoplastic transformation of the cell. For instance, endogenous mouse mammary tumor virus of some inbred lines appears to be the only causative agent in these mammary cancers. Other even nonpathogenic murine endogenous retroviruses are involved in the origination of MCF-type recombinant acute leukosis viruses. Some endogenous retroviruses are implicated in the transduction or activation of cellular protooncogenes. Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses. This problem is quite elaborated for chicken endogenous virus RAV-O (7-9).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Do Endogenous and Exogenous Action Control Compete for Perception?

    Science.gov (United States)

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  6. Endogenous Information, Risk Characterization, and the Predictability of Average Stock Returns

    Directory of Open Access Journals (Sweden)

    Pradosh Simlai

    2012-09-01

    Full Text Available In this paper we provide a new type of risk characterization of the predictability of two widely known abnormal patterns in average stock returns: momentum and reversal. The purpose is to illustrate the relative importance of common risk factors and endogenous information. Our results demonstrates that in the presence of zero-investment factors, spreads in average momentum and reversal returns correspond to spreads in the slopes of the endogenous information. The empirical findings support the view that various classes of firms react differently to volatility risk, and endogenous information harbor important sources of potential risk loadings. Taken together, our results suggest that returns are influenced by random endogenous information flow, which is asymmetric in nature, and can be used as a performance attribution factor. If one fails to incorporate the existing asymmetric endogenous information hidden in the historical behavior, any attempt to explore average stock return predictability will be subject to an unquantified specification bias.

  7. Do endogenous and exogenous action control compete for perception?

    Science.gov (United States)

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-04-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

  8. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    Neumaier, J.F.

    1989-01-01

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

  9. Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

    Science.gov (United States)

    Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

    2015-08-01

    Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells.

    Science.gov (United States)

    Fábryová, Helena; Hron, Tomáš; Kabíčková, Hana; Poss, Mary; Elleder, Daniel

    2015-11-01

    Endogenous retroviruses (ERVs) were acquired during evolution of their host organisms after infection and mendelian inheritance in the germline by their exogenous counterparts. The ERVs can spread in the host genome and in some cases they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is one of only a few well-defined examples of evolutionarily recent invasion of mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV integration sites have been detected in wild ranging mule deer (Odocoileus hemionus) host populations. Here, we describe for the first time induction of replication competent CrERV by cocultivation of deer and human cells. We characterize the physical properties and tropism of the induced virus. The genomic sequence of the induced virus is phylogenetically related to the evolutionarily young endogenous CrERVs described so far. We also describe the level of replication block of CrERV on deer cells and its capacity to establish superinfection interference. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Stochastic Stability of Endogenous Growth: Theory and Applications

    OpenAIRE

    Boucekkine, Raouf; Pintus, Patrick; Zou, Benteng

    2015-01-01

    We examine the issue of stability of stochastic endogenous growth. First, stochastic stability concepts are introduced and applied to stochastic linear homogenous differen- tial equations to which several stochastic endogenous growth models reduce. Second, we apply the mathematical theory to two models, starting with the stochastic AK model. It’s shown that in this case exponential balanced paths, which characterize optimal trajectories in the absence of uncertainty, are not robust to uncerta...

  12. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2018-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

  13. Endogenous growth theory and regional development policy

    Directory of Open Access Journals (Sweden)

    Cvetanović Slobodan

    2015-01-01

    Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.

  14. An endogenous Taylor condition in an endogenous growth monetary policy model

    OpenAIRE

    Le, Mai Vo; Gillman, Max; Minford, Patrick

    2007-01-01

    The paper derives a Taylor condition as part of the agent's equilibrium behavior in an endogenous growth monetary economy. It shows the assumptions necessary to make it almost identical to the original Taylor rule, and that it can interchangably take a money supply growth rate form. From the money supply form, simple policy experiments are conducted. A full central bank policy model is derived that includes the Taylor condition along with equations comparable to the standard aggregate-demand/...

  15. Revealing of endogenous Marinobufagin by an ultra-specific and sensitive UHPLC-MS/MS assay in pregnant women.

    Science.gov (United States)

    Lenaerts, Charline; Bond, Liz; Tuytten, Robin; Blankert, Bertrand

    2018-09-01

    Marinobufagenin (MBG) is a bufadienolide cardiac inotrope implicated in volume expansion-mediated hypertensive states including essential hypertension and preeclampsia (PE). Endogenous MBG is an inhibitor of the α1-isoform of Na + ,K + -ATPase with vasoconstrictive and cardiotonic properties, causing hypertension and natriuresis. Elevated endogenous MBG-like material levels have been described by immunoassays in salt-sensitive pregnant and preeclamptic rats as well as in preeclamptic human patients. The rise of endogenous MBG-like material appears prior the development of the main symptoms of PE, leading us to consider MBG as one of the potential biomarkers for PE. The weak specificity and the high variability of the published immunoassays gives no certification about endogenous MBG existence. This led us to set-up a highly specific and sensitive analytical method to detect MBG in plasma at low levels relying on liquid chromatography combined to mass spectrometry (UHPLC-MS/MS) with recording of 7 highly specific MRM transitions for MBG. Pure MBG standard used in the method development was obtained by purification from the Bufo marinus toad venom. d 3 -25-hydroxyvitamin D3 was used as internal standard. An increasing organic gradient with mobile phase A and B composed of 97:3 (v/v) H 2 O: MeOH and 50:45:5 (v/v/v) MeOH:IPA:H 2 O at pH 4.5 respectively was used on a Pursuit 3 PFP column (100 mm × 3 mm; 3 µm) to allow elution and separation of the plasmatic compounds. Chromatographic analyses of plasma samples were preceded by a precipitation of proteins pretreatment. The developed UHPLC-MS/MS assay has been applied to early-pregnant women plasma samples allowing us to investigate MBG plasma levels. Thanks to the high specificity of the assay we were able to authenticate and certify the presence of endogenous MBG in early-pregnant women plasma with the use of the 7 selected specific mass transitions. These pioneering preliminary results are giving a

  16. Role of endogenous thiols in protection

    Science.gov (United States)

    Vos, O.

    Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kep away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.

  17. Reference Pricing with Endogenous or Exogenous Payment Limits: Impacts on Insurer and Consumer Spending.

    Science.gov (United States)

    Brown, Timothy T; Robinson, James C

    2016-06-01

    Reference pricing (RP) theories predict different outcomes when reference prices are fixed (exogenous) versus being a function of market prices (MPs) (endogenous). Exogenous RP results in MPs at both high-price and low-price firms converging towards the reference price from above and below, respectively. Endogenous RP results in MPs at both high-price and low-price firms decreasing, with low-price firms acting strategically to decrease the reference price in order to gain market share. We extend these models to a hospital context focusing on insurer and consumer payments. Under exogenous RP, insurer and consumer payments to low-price hospitals increase, and insurer payments to high-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. Under endogenous RP, insurer payments to high-price and low-price hospitals decrease, and consumer payments to low-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. We test these predictions with difference-in-differences specifications using 2008-2013 data on patients undergoing joint replacement. For 2 years following RP implementation, insurer payments to high-price and low-price hospitals moved downward, consistent with endogenous RP. However, when the reference price was not reset to account for changes in MPs, insurer payments to low-price hospitals reverted to pre-implementation levels, consistent with exogenous RP. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Endogenous digitals-like factor in pregnant and non-pregnant women

    International Nuclear Information System (INIS)

    Clerico, A.; Del Chicca, M.G.; Balzan, S.; Strigini, F.; Melis, G.B.; Fruzzetti, F.; Bernardini, G.; Fioretti, P.

    1988-01-01

    Elevated plasma levels of an endogenous factor with digoxin-like immunoreactivity (DLIS) was recently found in pregnant women, and it has been postulated to play a role in the regulation of fluids and electrolytes, as well as in the pathogenesis of hypertensive disorders in pregnancy. The authors have studied the plasma levels of DLIS in normal women (before and after treatment with contraceptive pills) and in pregnant women (either normotensive or hypertensive), during the gestional and the post-partum period using a sensitive RIA method. In addition, the authors have measured the inhibition of binding activity of 3 H-ouabain to intact erythrocytes in 7 plasma samples collected from healthy adults and in 5 plasma samples of women in the second or third trimester of pregnancy. In 8 normal cycling women DLIS levels were similar during the follicular phase (24.9±6.2 pg/ml d.e.) and the luteal phase (22.6±4.7 pg/ml d.e.9. Six months treatment with different preparations of contraceptive pills did not affect the concentrations of DLIS. In a cross-sectional study performed on 171 healthy pregnant women a significant increase (p 3 Houbain extracts of pregnant women as compared to normal adults, with a significant correlation between the data obtained with RIA and RRA method. On the other hand, no significant differences in DLIS levels were found between singleton and 9 twin pregnancies, and also between non-hypertensive and 8 hypertensive pregnant women. This data confirm that the plasma concentration of an endogenous factor (or a group of substances) with cardiac glycoside-like activity is significantly increased in pregnant women. However, further studies are necessary to well charcterize the possible role of DLIS in the pathphysiology of hypertension in pregnancy

  19. Anti-colitis and -adhesion effects of daikenchuto via endogenous adrenomedullin enhancement in Crohn's disease mouse model.

    Science.gov (United States)

    Kono, Toru; Kaneko, Atsushi; Hira, Yoshiki; Suzuki, Tatsuya; Chisato, Naoyuki; Ohtake, Nobuhiro; Miura, Naoko; Watanabe, Tsuyoshi

    2010-06-01

    Adrenomedullin (ADM) is a member of the calcitonin family of regulatory peptides, and is reported to have anti-inflammatory effects in animal models of Crohn's disease (CD). We investigated the therapeutic effects of daikenchuto (DKT), an extracted Japanese herbal medicine, on the regulation of endogenous ADM in the gastrointestinal tract in a CD mouse model. Colitis was induced in mice by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS); afterwards, DKT was given orally. Colonic damage was assessed on day 3 by macroscopic and microscopic observation, enzyme immunoassays of proinflammatory cytokines in the colonic mucosa, and serum amyloid A (SAA), a hepatic acute-phase protein. To determine the involvement of ADM, an ADM antagonist was instilled intrarectally before DKT administration. The effect of DKT on ADM production by intestinal epithelial cells was evaluated by enzyme immunoassay and real-time PCR. DKT significantly attenuated mucosal damage and colonic inflammatory adhesions, and inhibited elevations of SAA in plasma and the proinflammatory cytokines TNFα and IFNγ in the colon. Small and large intestinal epithelial cells produced higher levels of ADM after DKT stimulation. A DKT-treated IEC-6 cell line also showed enhanced ADM production at protein and mRNA levels. Abolition of this effect by pretreatment with an ADM antagonist shows that DKT appears to exert its anti-colitis effect via up-regulation of endogenous ADM in the intestinal tract. DKT exerts beneficial effects in a CD mouse model through endogenous release and production of ADM. Endogenous ADM may be a therapeutic target for CD. Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  20. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.