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Sample records for prevent sympathetically mediated

  1. Sympathetic mediated vasomotion and skin capillary permeability in diabetic patients with peripheral neuropathy

    NARCIS (Netherlands)

    Lefrandt, JD; Hoeven, JH; Roon, AM; Smit, AJ; Hoogenberg, K

    Aims/hypothesis. A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary

  2. Sympathetic Response to Insulin is Mediated by Melanocortin 3/4 Receptors in the Hypothalamic Paraventricular Nucleus

    OpenAIRE

    Ward, Kathryn R.; Bardgett, James F.; Wolfgang, Lawrence; Stocker, Sean D.

    2011-01-01

    Hyperinsulinemia increases sympathetic nerve activity and contributes to cardiovascular dysfunction in obesity and diabetes. Neurons of the hypothalamic paraventricular nucleus regulate sympathetic nerve activity through mono- and poly-synaptic connections to preganglionic neurons in the spinal cord. The purpose of the present study was to determine whether hypothalamic paraventricular nucleus neurons mediate the sympathetic response to insulin. Hyperinsulinemic-euglycemic clamps were perform...

  3. An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation.

    Science.gov (United States)

    Ryu, Yun Kyoung; Collins, Sarah Ellen; Ho, Hsin-Yi Henry; Zhao, Haiqing; Kuruvilla, Rejji

    2013-05-01

    During nervous system development, axon branching at nerve terminals is an essential step in the formation of functional connections between neurons and target cells. It is known that target tissues exert control of terminal arborization through secretion of trophic factors. However, whether the in-growing axons themselves produce diffusible cues to instruct target innervation remains unclear. Here, we use conditional mutant mice to show that Wnt5a derived from sympathetic neurons is required for their target innervation in vivo. Conditional deletion of Wnt5a resulted in specific deficits in the extension and arborization of sympathetic fibers in their final target fields, while no defects were observed in the overall tissue patterning, proliferation, migration or differentiation of neuronal progenitors. Using compartmentalized neuronal cultures, we further demonstrate that the Ror receptor tyrosine kinases are required locally in sympathetic axons to mediate Wnt5a-dependent branching. Thus, our study suggests an autocrine Wnt5a-Ror signaling pathway that directs sympathetic axon branching during target innervation. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Subfornical Organ Mediates Sympathetic and Hemodynamic Responses to Blood-borne Pro-Inflammatory Cytokines

    Science.gov (United States)

    Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G.; Yu, Yang; Johnson, Alan Kim; Felder, Robert B.

    2013-01-01

    Pro-inflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) act upon the brain to increase blood pressure (BP), heart rate (HR) and sympathetic nerve activity. These molecules are too large to penetrate blood brain barrier (BBB), and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a BBB, plays a major role in mediating the sympathetic and hemodynamic responses to circulating pro-inflammatory cytokines. Intracarotid artery (ICA) injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean BP (MBP), HR and renal sympathetic nerve activity (RSNA) in rats with sham lesions of the SFO (SFO-s). These excitatory responses to ICA TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in MBP, HR and RSNA in response to intravenous (IV) injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating pro-inflammatory cytokines act to elicit cardiovascular and sympathetic responses. PMID:23670302

  5. [Vitamin C and prevention of reflex sympathetic dystrophy following surgical management of distal radius fractures].

    Science.gov (United States)

    Cazeneuve, J F; Leborgne, J M; Kermad, K; Hassan, Y

    2002-12-01

    Reflex sympathetic dystrophy is a major complication following surgical treatment of fractures of the distal radius. Its pathogenesis is related to lipid peroxidation which damages vascular endothelial cells, increasing capillary permeability. Vitamin C is a natural antioxidant. The authors have made a comparative study of two groups of patients with isolated closed displaced fractures of the distal radius, which were reduced and stabilized by intrafocal pinning. Group 1 included 100 patients who were treated from 1995 until 1998 and who did not receive any vitamin C supplementation; group 2 included 95 patients who were treated from 1999 to 2002 and who received daily administration of one gram vitamin C orally during 45 days, starting on the day of fracture. The incidence of reflex sympathetic dystrophy was five time times lower in group 2 (2.1% versus 10%). This is in line with previous observations and lends credit to the value of vitamin C administration as a prophylactic measure to prevent the occurrence of reflex sympathetic dystrophy in patients who undergo surgical treatment of a displaced fracture of the distal radius.

  6. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents.

    Science.gov (United States)

    Madsen, Andreas N; Jelsing, Jacob; van de Wall, Esther H E M; Vrang, Niels; Larsen, Philip J; Schwartz, Gary J

    2009-01-02

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac-superior mesenteric ganglionectomy (CGX). Irrespective of the operational procedure, rimonabant (10mg/kg) effectively reduced standard chow as well as palatable diet (ensure) intake. In conclusion, the data clearly demonstrate that neither vagal gut afferents, nor gut afferents traveling via the sympathetic nervous system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia.

  7. Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.

    Science.gov (United States)

    Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z

    2014-06-01

    The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.

  8. Central nervous system neuropeptide Y regulates mediators of hepatic phospholipid remodeling and very low-density lipoprotein triglyceride secretion via sympathetic innervation

    Directory of Open Access Journals (Sweden)

    Jennifer M. Rojas

    2015-03-01

    Conclusions: These data support a model in which CNS NPY modulates mediators of hepatic PL remodeling and VLDL maturation to stimulate VLDL-TG secretion that is dependent on the Y1 receptor and sympathetic signaling to the liver.

  9. Exercise training can prevent cardiac hypertrophy induced by sympathetic hyperactivity with modulation of kallikrein-kinin pathway and angiogenesis.

    Directory of Open Access Journals (Sweden)

    José Antônio Silva

    Full Text Available Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg(-1 day-(1; and trained group (Iso+Exe which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.

  10. Hypothalamic CRF and Norepinephrine Mediate Sympathetic and Cardiovascular Responses to Acute Intracarotid Injection of TNF-α in the Rat

    Science.gov (United States)

    Zhang, Zhi-Hua; Felder, Robert B.

    2009-01-01

    Systemic administration of tumour necrosis factor - alpha (TNF-α) induces the release of norepinephrine (NE) in the paraventricular nucleus (PVN) of hypothalamus and an increase in expression of corticotrophin-releasing-factor (CRF) and CRF type 1 receptors. We explored the hypothesis that CRF and NE in PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF-α. In anaesthetised rats, the increases in arterial pressure and heart rate induced by intracarotid artery injection of TNF-α were attenuated by intracerebroventricular (ICV) injection of either the α1-adrenergic antagonist prazosin or the CRF antagonist α-helical CRF. Prazosin blocked the TNF-α-induced increase in renal sympathetic nerve activity (RSNA), while α-helical CRF substantially reduced the RSNA response. Conversely, CRF and the α1-adrenergic agonist phenylephrine (PE), administered ICV, both elicited increases in PVN neuronal activity, RSNA, arterial pressure and heart rate. Microinjection of CRF and PE directly into PVN evoked smaller responses. These results are consistent with the hypothesis that NE and CRF in the PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF-α. PMID:18777604

  11. Using an electronic detonator system and expanded blast patterns to prevent sympathetic detonation at Powder River Basin coal mines

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.; Fleetwood, K.; Haid, J. [Orica USA Inc., Watkins, CO (United States). Advanced Mining Solutions

    2005-07-01

    This paper describes a systematic approach to prevent cast blast holes from detonating sympathetically through the use of the electronic initiation and expanded blast patterns. In-situ measurements were recorded from pressure probes, velocity of detonation probes and near field accelerometers, along with digital images generated from a high speed CCD camera. Large diameter angled drill holes were also checked for any measurable amount of deviation by a cable type borehole measurement tool. The field measurements provided the scientific evidence, statistical data, and documentation necessary to develop a sound method or a 'road map' that would minimize and in some situations prevent the occurrence of blast hole sympathetic detonation. 2 refs., 3 figs.

  12. Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans.

    NARCIS (Netherlands)

    Atkinson, C.L.; Lewis, N.C.; Carter, H.H.; Thijssen, D.H.J.; Ainslie, P.N.; Green, D.J.

    2015-01-01

    KEY POINTS: Previous studies indicate a transient reduction in arterial function following large muscle group exercise, but the mechanisms involved are unknown. Sympathetic nervous system activation may contribute to such reductions through direct effects in the artery wall, or because of decreases

  13. Histamine H3 receptors mediate inhibition of noradrenaline release from intestinal sympathetic nerves

    OpenAIRE

    Blandizzi, Corrado; Tognetti, Martina; Colucci, Rocchina; Tacca, Mario Del

    2000-01-01

    The present study investigates whether presynaptic histamine receptors regulate noradrenaline release from intestinal sympathetic nerves. The experiments were performed on longitudinal muscle-myenteric plexus preparations of guinea-pig ileum, preincubated with [3H]-noradrenaline.In the presence of rauwolscine, electrically-induced [3H]-noradrenaline release was inhibited by histamine or R-α-methylhistamine, whereas it was unaffected by pyridylethylamine, impromidine, pyrilamine, cimetidine, t...

  14. Decreased expression of neuronal nitric oxide synthase in the nucleus tractus solitarii inhibits sympathetically mediated baroreflex responses in rat

    Science.gov (United States)

    Lin, Li-Hsien; Nitschke Dragon, Deidre; Jin, Jingwen; Tian, Xin; Chu, Yi; Sigmund, Curt; Talman, William T

    2012-01-01

    Despite numerous studies it remains controversial whether nitric oxide (NO·) synthesized by neuronal NOS (nNOS) plays an excitatory or inhibitory role in transmission of baroreflex signals in the nucleus tractus solitarii (NTS). In the current studies we sought to test the hypothesis that nNOS is involved in excitation of baroreflex pathways in NTS while excluding pharmacological interventions in assessing the influence of nNOS. We therefore developed, validated and utilized a short hairpin RNA (shRNA) to reduce expression of nNOS in the NTS of rats whose baroreflex activity was then studied. We demonstrate downregulation of nNOS through transduction with adeno-associated virus type 2 (AAV2) carrying shRNA for nNOS. When injected bilaterally into NTS AAV2nNOSshRNA significantly reduced reflex tachycardic responses to acute hypotension while not affecting reflex bradycardic responses to acute increases of arterial pressure. Control animals treated with intravenous propranolol to block sympathetically mediated chronotropic responses manifested the same baroreflex responses as animals that had been treated with AAV2nNOSshRNA. Neither AAV2 eGFP nor AAV2nNOScDNA affected baroreflex responses. Blocking cardiac vagal influences with atropine similarly reduced baroreflex-mediated bradycardic responses to increases in arterial pressure both in control animals and in those treated with AAV2nNOSshRNA. We conclude that NO· synthesized by nNOS in the NTS is integral to excitation of baroreflex pathways involved in reflex tachycardia, a largely sympathetically mediated response, but not reflex bradycardia, a largely parasympathetically mediated response. We suggest that, at the basal state, nNOS is maximally engaged. Thus, its upregulation does not augment the baroreflex. PMID:22687614

  15. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

    Science.gov (United States)

    Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

    2013-03-19

    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

  16. Mediation designs for tobacco prevention research

    Science.gov (United States)

    MacKinnon, David P.; Taborga, Marcia P.; Morgan-Lopez, Antonio A.

    2010-01-01

    This paper describes research designs and statistical analyses to investigate how tobacco prevention programs achieve their effects on tobacco use. A theoretical approach to program development and evaluation useful for any prevention program guides the analysis. The theoretical approach focuses on action theory for how the program affects mediating variables and on conceptual theory for how mediating variables are related to tobacco use. Information on the mediating mechanisms by which tobacco prevention programs achieve effects is useful for the development of efficient programs and provides a test of the theoretical basis of prevention efforts. Examples of these potential mediating mechanisms are described including mediated effects through attitudes, social norms, beliefs about positive consequences, and accessibility to tobacco. Prior research provides evidence that changes in social norms are a critical mediating mechanism for successful tobacco prevention. Analysis of mediating variables in single group designs with multiple mediators are described as well as multiple group randomized designs which are the most likely to accurately uncover important mediating mechanisms. More complicated dismantling and constructive designs are described and illustrated based on current findings from tobacco research. Mediation analysis for categorical outcomes and more complicated statistical methods are outlined. PMID:12324176

  17. Hypoxia mediated pulmonary edema: potential influence of oxidative stress, sympathetic activation and cerebral blood flow.

    Science.gov (United States)

    Khademi, Shadi; Frye, Melinda A; Jeckel, Kimberly M; Schroeder, Thies; Monnet, Eric; Irwin, Dave C; Cole, Patricia A; Bell, Christopher; Miller, Benjamin F; Hamilton, Karyn L

    2015-10-09

    Neurogenic pulmonary edema (NPE) is a non-cardiogenic form of pulmonary edema that can occur consequent to central neurologic insults including stroke, traumatic brain injury, and seizure. NPE is a public health concern due to high morbidity and mortality, yet the mechanism(s) are unknown. We hypothesized that NPE, evoked by cerebral hypoxia in the presence of systemic normoxia, would be accompanied by sympathetic activation, oxidative stress, and compensatory antioxidant mechanisms. Thirteen Walker hounds were assigned to cerebral hypoxia (SaO2 ~ 55 %) with systemic normoxia (SaO2 ~ 90 %) (CH; n = 6), cerebral and systemic (global) hypoxia (SaO2 ~ 60 %) (GH; n = 4), or cerebral and systemic normoxia (SaO2 ~ 90 %) (CON; n = 3). Femoral venous (CH and CON) perfusate was delivered via cardiopulmonary bypass to the brain and GH was induced by FiO2 = 10 % to maintain the SaO2 at ~60 %. Lung wet to lung dry weight ratios (LWW/LDW) were assessed as an index of pulmonary edema in addition to hemodynamic measurements. Plasma catecholamines were measured as markers of sympathetic nervous system (SNS) activity. Total glutathione, protein carbonyls, and malondialdehyde were assessed as indicators of oxidative stress. Brain and lung compensatory antioxidants were measured with immunoblotting. Compared to CON, LWW/LDW and pulmonary artery pressure were greater in CH and GH. Expression of hemeoxygenase-1 in brain was higher in CH compared to GH and CON, despite no group differences in oxidative damage in any tissue. Catecholamines tended to be higher in CH and GH. Cerebral hypoxia, with systemic normoxia, is not systematically associated with an increase in oxidative stress and compensatory antioxidant enzymes in lung, suggesting oxidative stress did not contribute to NPE in lung. However, increased SNS activity may play a role in the induction of NPE during hypoxia.

  18. Polyethyleneimine-mediated transfection of cultured postmitotic neurons from rat sympathetic ganglia and adult human retina

    Directory of Open Access Journals (Sweden)

    Higgins Dennis

    2001-02-01

    Full Text Available Abstract Background Chemical methods of transfection that have proven successful with cell lines often do not work with primary cultures of neurons. Recent data, however, suggest that linear polymers of the cation polyethyleneimine (PEI can facilitate the uptake of nucleic acids by neurons. Consequently, we examined the ability of a commercial PEI preparation to allow the introduction of foreign genes into postmitotic mammalian neurons. Sympathetic neurons were obtained from perinatal rat pups and maintained for 5 days in vitro in the absence of nonneuronal cells. Cultures were then transfected with varying amounts of a plasmid encoding either E. coli β-galactosidase or enhanced green fluorescence protein (EGFP using PEI. Results Optimal transfection efficiency was observed with 1 μg/ml of plasmid DNA and 5 μg/ml PEI. Expression of β-galactosidase was both rapid and stable, beginning within 6 hours and lasting for at least 21 days. A maximum yield was obtained within 72 hours with ∼ 9% of the neurons expressing β-galactosidase, as assessed by both histochemistry and antibody staining. Cotransfection of two plasmids encoding reporter genes was achieved. Postmitotic neurons from adult human retinal cultures also demonstrated an ability to take up and express foreign DNA using PEI as a vector. Conclusions These data suggest that PEI is a useful agent for the stable expression of plasmid-encoded genes in neuronal cultures.

  19. Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure.

    Science.gov (United States)

    Abukar, Yonis; May, Clive N; Ramchandra, Rohit

    2016-01-01

    Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF. Copyright © 2016 the American Physiological Society.

  20. Age-related weakening of baroreflex-mediated sympathetic activity in spontaneously hypertensive rats in response to blood pressure reduction.

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    Prados, P; Santa, T; Fukushima, T; Homma, H; Kasai, C; Martin, M A; del Castillo, B; Imai, K

    1998-09-01

    Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate, and the concentration of plasma catecholamines (CAs), norepinephrine (NE), and epinephrine (E) were concomitantly determined, and the correlations between these three variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic

  1. Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

    Science.gov (United States)

    Groehs, Raphaela V; Toschi-Dias, Edgar; Antunes-Correa, Ligia M; Trevizan, Patrícia F; Rondon, Maria Urbana P B; Oliveira, Patrícia; Alves, Maria J N N; Almeida, Dirceu R; Middlekauff, Holly R; Negrão, Carlos E

    2015-05-01

    Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P training prevents the deterioration of ABRMSNA in CHF patients. Copyright © 2015 the American Physiological Society.

  2. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M

    2009-01-01

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

  3. Leg muscle reflexes mediated by cutaneous A-beta fibres are normal during gait in reflex sympathetic dystrophy.

    Science.gov (United States)

    van der Laan, L; Boks, L M; van Wezel, B M; Goris, R J; Duysens, J E

    2000-04-01

    Reflex sympathetic dystrophy (RSD) is, from the onset, characterized by various neurological deficits such as an alteration of sensation and a decrease in muscle strength. We investigated if afferent A-beta fibre-mediated reflexes are changed in lower extremities affected by acute RSD. The involvement of these fibres was determined by analyzing reflex responses from the tibialis anterior (TA) and biceps femoris (BF) muscles after electrical stimulation of the sural nerve. The reflexes were studied during walking on a treadmill to investigate whether the abnormalities in gait of the patients were related either to abnormal amplitudes or deficient phase-dependent modulation of reflexes. In 5 patients with acute RSD of the leg and 5 healthy volunteers these reflex responses were determined during the early and late swing phase of the step cycle. No significant difference was found between the RSD and the volunteers. During early swing the mean amplitude of the facilitatory P2 responses in BF and TA increased as a function of stimulus intensity (1.5, 2 and 2.5 times the perception threshold) in both groups. At end swing the same stimuli induced suppressive responses in TA. This phase-dependent reflex reversal from facilitation in early swing to suppression in late swing occurred equally in both groups. In the acute phase of RSD of the lower extremity there is no evidence for abnormal A-beta fibre-mediated reflexes or for defective regulation of such reflexes. This finding has implications for both the theory on RSD pathophysiology and RSD models, which are based on abnormal functioning of A-beta fibres.

  4. Reflex sympathetic dystrophy in hemiplegia.

    Science.gov (United States)

    Gokkaya, Nilufer Kutay Ordu; Aras, Meltem; Yesiltepe, Elcin; Koseoglu, Fusun

    2006-12-01

    There is a high incidence of reflex sympathetic dystrophy of the upper limbs in patients with hemiplegia, and its painful and functional consequences present a problem to specialists in physical medicine and rehabilitation. This study was designed to assess the role of several factors in the occurrence of reflex sympathetic dystrophy in patients with hemiplegia. Ninety-five consecutive stroke patients (63 male and 32 female, mean age 59+/-12 years) admitted to our hospital were evaluated. Of the study group, 29 patients (30.5%) were found to develop reflex sympathetic dystrophy. There were no significant differences between the hemiplegic patient groups with or without reflex sympathetic dystrophy regarding age, gender, etiology, side of involvement, disease duration and the presence of comorbidities. The recovery stages of hemiplegia, as shown by Brunnstrom functional classification, were significantly different between the two groups; patients in lower recovery stages tended to develop reflex sympathetic dystrophy more frequently (Preflex sympathetic dystrophy. Glenohumeral subluxation was present in 37 patients (38.9%) in our study group and the presence of this complication was related to the occurrence of reflex sympathetic dystrophy. The presence of glenohumeral subluxation was significantly higher in patients with reflex sympathetic dystrophy (21/29, 72.4%) when compared to the patients without reflex sympathetic dystrophy (16/66, 24.2%) (Preflex sympathetic dystrophy. These results suggest that lower recovery stages, reduced tonus and glenohumeral subluxation significantly contribute to the occurrence of reflex sympathetic dystrophy in the hemiplegic patient. We believe that preventive and treatment measures should consider these factors as they seem to have in common a higher risk of traumatizing the paralyzed upper limb and causing reflex sympathetic dystrophy.

  5. Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Castro, E.F.S. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mostarda, C.T. [Universidade Federal do Maranhão, São Luís, MA (Brazil); Rodrigues, B. [Laboratório do Movimento Humano, Universidade São Judas Tadeu, São Paulo, SP (Brazil); Moraes-Silva, I.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Feriani, D.J. [Laboratório do Movimento Humano, Universidade São Judas Tadeu, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-13

    The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg{sup 2}), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg{sup 2}). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

  6. Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

    International Nuclear Information System (INIS)

    Castro, E.F.S.; Mostarda, C.T.; Rodrigues, B.; Moraes-Silva, I.C.; Feriani, D.J.; De Angelis, K.; Irigoyen, M.C.

    2015-01-01

    The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg 2 ), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg 2 ). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement

  7. Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

    Directory of Open Access Journals (Sweden)

    Dianne Lorton

    2015-03-01

    Full Text Available Cross-talk between the sympathetic nervous system (SNS and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs in immune cells activates the cAMP-protein kinase A (PKA intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells.

  8. Reflex sympathetic dystrophy.

    Science.gov (United States)

    Miller, Ruth L S

    2003-01-01

    Reflex sympathetic dystrophy, also known as complex regional pain syndrome type I, is a multisymptom syndrome usually affecting one or more extremities. It is inadequately understood and, therefore, often frustrating to treat. This article presents a case study of a 23-year career nurse who developed reflex sympathetic dystrophy of the left knee. It also reviews the rationale for reflex sympathetic dystrophy, treatment, and life-care planning for a patient with reflex sympathetic dystrophy.

  9. Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

    Science.gov (United States)

    García-González, P; Fabregat-Andrés, Ó; Cozar-Santiago, P; Sánchez-Jurado, R; Estornell-Erill, J; Valle-Muñoz, A; Quesada-Dorador, A; Payá-Serrano, R; Ferrer-Rebolleda, J; Ridocci-Soriano, F

    2016-01-01

    Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  10. Sympathetic skin responses in reflex sympathetic dystrophy.

    Science.gov (United States)

    Bolel, K; Hizmetli, S; Akyüz, A

    2006-07-01

    This study was performed to determine the utility of sympathetic skin response (SSR) in evaluating the sympathetic function and to follow up the effects of sympathetic blockade in reflex sympathetic dystrophy (RSD). Thirty patients having RSD with upper extremity involvement were randomly divided into two groups. Besides medical therapy and exercise, physical therapy agents were applied to both the groups. In addition to this treatment protocol, stellar ganglion blockade was done by diadynamic current in Group II. The normal sides of the patients were used for the control group. SSRs were measured in all the patients before and after the therapy. The amplitude was found to be increased and the latency was found to be decreased in the affected side in both the groups before the therapy. After the therapy, the amplitude was decreased and latency was increased in both the groups. But, the differences in amplitude (P = 0.001) and latency (P = 0.002) before and after the therapy were significantly higher in Group II. (Before the treatment, SSRs were significantly different between the normal and the affected sides in both the groups. The observed change in SSRs after the treatment was higher in Group II.) It was concluded that, SSR can be a useful and noninvasive method in diagnosing the sympathetic dysfunction in RSD and can be used for evaluating the response to sympathetic blockade and other treatment modalities.

  11. Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons.

    Science.gov (United States)

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J

    2015-07-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Interventional management of intractable sympathetically mediated pain by computed tomography-guided catheter implantation for block and neuroablation of the thoracic sympathetic chain: technical approach and review of 322 procedures.

    Science.gov (United States)

    Agarwal-Kozlowski, K; Lorke, D E; Habermann, C R; Schulte am Esch, J; Beck, H

    2011-08-01

    We retrospectively evaluated the safety and efficacy of computed tomography-guided placement of percutaneous catheters in close proximity to the thoracic sympathetic chain by rating pain intensity and systematically reviewing charts and computed tomography scans. Interventions were performed 322 times in 293 patients of mean (SD) age 59.4 (17.0) years, and male to female ratio 105:188, with postherpetic neuralgia (n = 103, 35.1%), various neuralgias (n = 88, 30.0%), complex regional pain syndrome (n = 69, 23.6%), facial pain (n = 17, 5.8%), ischaemic limb pain (n = 7, 2.4%), phantom limb pain (n = 4, 1.4%), pain following cerebrovascular accident (n = 2, 0.7%), syringomyelia (n = 2, 0.7%) and palmar hyperhidrosis (n = 1, 0.3%). The interventions were associated with a total of 23 adverse events (7.1% of all procedures): catheter dislocation (n = 9, 2.8%); increase in pain intensity (n = 8, 2.5%); pneumothorax (n = 3, 0.9%); local infection (n = 2, 0.6%); and puncture of the spinal cord (n = 1, 0.3%). Continuous infusion of 10 ml.h(-1) ropivacaine 0.2% through the catheters decreased median (IQR [range]) pain scores from 8 (6-9 [2-10]) to 2 (1-3 [0-10]) (p < 0.0001). Chemical neuroablation was necessary in 137 patients (46.8%). We conclude that this procedure leads to a significant reduction of pain intensity in otherwise obstinate burning or stabbing pain and is associated with few hazards. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  13. Mechanisms of insulin action on sympathetic nerve activity

    Science.gov (United States)

    Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

    1996-01-01

    Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

  14. Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions.

    Science.gov (United States)

    Salman, Ibrahim M; Ameer, Omar Z; Sattar, Munavvar A; Abdullah, Nor A; Yam, Mun F; Najim, Hafsa S; Khan, Abdul Hye; Johns, Edward J

    2010-04-01

    We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury. Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded. Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats). The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions.

  15. [Professional outcome of reflex sympathetic dystrophy].

    Science.gov (United States)

    Dauty, M; Renaud, P; Deniaud, C; Tortellier, L; Dubois, C

    2001-03-01

    In spite of physical medicine and rehabilitation care, post-traumatic reflex sympathetic dystrophy can be at the origin of articular deficiency, which decrease the capacity to return to work. The aim of this study is to know the professional future of patients who present post-traumatic reflex sympathetic dystrophy. Eighteen months prospective study, carried out from patients in age to work, hospitalized in physical medicine and rehabilitation unit for ostéo-articular traumatism complicated by reflex sympathetic dystrophy. Description of the population and comorbidity factors preventing professional resumption. Determination of the duration of medical certificate and the modalities of professional resumption. From 16 patients in age to work, only 12 were able to resume a full time profession with an average period of 10.5 months +/- 5. The importance of the, the distale articular location of reflex sympathetic dystrophy (wrist - hand, ankle - foot), the association with a comorbidity such as chronic alcoholism represent pejorative factors of working resumption. Organizations of workstation are often necessary in six cases over eight, if the job is not sedentary. In the most complicated cases, inaptitudes in the work are pronounced with demand of professional reclassifying. Post-traumatic reflex sympathetic dystrophy represents a real challenge for the rehabilitation team, to minimize deficiencies and to help the patient to become again a worker.

  16. Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine.

    Science.gov (United States)

    Pirzgalska, Roksana M; Seixas, Elsa; Seidman, Jason S; Link, Verena M; Sánchez, Noelia Martínez; Mahú, Inês; Mendes, Raquel; Gres, Vitka; Kubasova, Nadiya; Morris, Imogen; Arús, Bernardo A; Larabee, Chelsea M; Vasques, Miguel; Tortosa, Francisco; Sousa, Ana L; Anandan, Sathyavathy; Tranfield, Erin; Hahn, Maureen K; Iannacone, Matteo; Spann, Nathanael J; Glass, Christopher K; Domingos, Ana I

    2017-11-01

    The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron-associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment.

  17. Electrodermal response in nonglabrous skin of freely moving rats: mediation by the sympathetic nervous system and evaluation in an animal model of depression.

    Science.gov (United States)

    Guinjoan, S M; Yannielli, P C; Lococco, J; Siri, L N; Cardinali, D P

    1996-01-01

    Electrodermal responses in the facial region of freely moving rats were recorded bilaterally. After a nociceptive stimulus (ammonia vapor exposure), the response (a transient negative potential followed by a longer-lasting positive potential) attained a similar amplitude on both sides. Surgical sympathetic denervation of facial skin by ipsilateral superior cervical ganglionectomy (SCGx) significantly decreased the electrodermal response. When an inferior cervical ganglionectomy was performed in addition to SCGx, a further decrease in electrodermal response was observed. Pretreatment of unilaterally SCGx rats with atropine blunted the electrical response in the control side to levels similar to those found in the SCGx side. Treatment with phenoxybenzamine or propranolol was ineffective. Skin potential responses were measured in adult rats administered with clomipramine from the 8th to the 21st day of life and exhibiting a long-lasting syndrome resembling human depression. Clomipramine-injected rats developed larger skin potential responses to sound stimulation than controls while responses to ammonia vapor were similar in both groups, as well as the habituation rate after repetitive exposure to ammonia vapor. The results indicate that some of the altered electrodermal responses found in depressed patients are detectable in the clomipramine animal model of endogenous depression.

  18. Sympathetic chain Schwannoma

    International Nuclear Information System (INIS)

    Al-Mashat, Faisal M.

    2009-01-01

    Schwannomas are rare, benign, slowly growing tumors arising from Schwann cells that line nerve sheaths. Schwannomas arising from the cervical sympathetic chain are extremely rare. Here, we report a case of a 70-year-old man who presented with only an asymptomatic neck mass. Physical examination revealed a left sided Horner syndrome and a neck mass with transmitted pulsation and anterior displacement of the carotid artery. Computed tomography (CT) showed a well-defined non-enhancing mass with vascular displacement. The nerve of origin of this encapsulated tumor was the sympathetic chain. The tumor was excised completely intact. The pathologic diagnosis was Schwannoma (Antoni type A and Antoni type B). The patient has been well and free of tumor recurrence for 14 months with persistence of asymptomatic left sided Horner syndrome. The clinical, radiological and pathological evaluations, therapy and postoperative complications of this tumor are discussed. (author)

  19. Sympathetic nervous system and spaceflight

    Science.gov (United States)

    Cooke, William H.; Convertino, Victor A.

    2007-02-01

    Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

  20. Normal sympathetic nervous system response in reflex sympathetic dystrophy.

    Science.gov (United States)

    Figuerola, María de Lourdes; Levin, Gloria; Bertotti, Alicia; Ferreiro, Jorge; Barontini, Marta

    2002-01-01

    We evaluated sympathetic nervous system activity by sympathetic skin response (SSR) recording and we further investigated sympathetic and opioid outflow indirectly in patients with features of reflex sympathetic dystrophy by measuring concentrations of plasma catecholamines (CAs) and their metabolites and plasma metenkephalin (ME), before and after corticoid treatment. Six patients were studied. Basal SSR latencies, morphologies and amplitudes were normal in five patients. In one woman, latency and amplitude were also normal but the morphology was disturbed. Basal plasma ME, CA and metabolite levels were similar in the affected and non-affected limbs and a significant increase in plasma ME concentrations was observed in both affected and non-affected limbs after two weeks of steroid treatment. Altogether these results point to an adaptive supersensitivity rather than a sympathetic hyperactivity in this syndrome; also, they indicate that the therapeutic effect of steroids adds, to their known anti-inflammatory action, a stimulatory action on the endogenous opioid system.

  1. Intracranial Pressure Is a Determinant of Sympathetic Activity.

    Science.gov (United States)

    Schmidt, Eric A; Despas, Fabien; Pavy-Le Traon, Anne; Czosnyka, Zofia; Pickard, John D; Rahmouni, Kamal; Pathak, Atul; Senard, Jean M

    2018-01-01

    considered as a physiological stressor, driving sympathetic activity. The results suggest a novel physiological ICP-mediated sympathetic modulation circuit and the existence of a possible intracranial (i.e., central) baroreflex. Modest ICP rise might participate to the pathophysiology of cardio-metabolic homeostasis imbalance with sympathetic over-activity, and to the pathogenesis of sympathetically-driven diseases.

  2. AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

    NARCIS (Netherlands)

    GEERTZEN, JHB; EISMA, WH

    Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

  3. Mineralocorticoid Receptors, Inflammation and Sympathetic Drive in Heart Failure

    Science.gov (United States)

    Felder, Robert B.

    2010-01-01

    Appreciation for the role of aldosterone and mineralocorticoid receptors in cardiovascular disease is accelerating rapidly. Recent experimental work has unveiled a strong relationship between brain mineralocorticoid receptors and sympathetic drive, an important determinant of outcome in heart failure and hypertension. Two putative mechanisms are explored in this manuscript. First, brain mineralocorticoid receptors may influence sympathetic discharge by regulating the release of pro-inflammatory cytokines into the circulation. Blood-borne pro-inflammatory cytokines act upon receptors in the microvasculature of the brain to induce cyclooxygenase-2 activity and the production of prostaglandin E2, which penetrates the blood-brain barrier to activate the sympathetic nervous system. Second, brain mineralocorticoid receptors may influence sympathetic drive by upregulating the activity of the brain renin-angiotensin system, resulting in NAD(P)H oxidase dependent superoxide production. A potential role for superoxide dependent mitogen-activated protein kinase signaling pathways in the regulation of sympathetic nerve activity is also considered. Other potential downstream signaling mechanisms contributing to mineralocorticoid receptor mediated sympathetic excitation are under investigation. PMID:19648480

  4. Role of sympathetic nerve activity in the process of fainting

    Directory of Open Access Journals (Sweden)

    Satoshi eIwase

    2014-09-01

    Full Text Available Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression will be described with two types of sympathetic change. Simultaneous recordings of microneurographically recorded MSNA and continuous and noninvasive blood pressure measurement have disclose what is going on in the course of progression of the syncope. Vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. The vasovagal syncope is characterized by the sympathoexcitation, followed by vagal overcome via the Bezold-Jarisch reflex. Orthostatic syncope is caused by the response failure or lack of sympathetic nerve activity toward the orthostatic challenge followed by the fluid shift, and subsequent cerebral low perfusion. Four causes are considered for the compensatory failure, which triggers the orthostatic syncope; hypovolemia, increased pooling in the lower body, failure to activate the sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions were described in the viewpoint of 1 exaggerated sympathoexcitation and 2 failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control the cardiovascular function, and its failure resulted syncope, however, responses of the system by microneurographically recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

  5. Suppression of sympathetic detonation

    Science.gov (United States)

    Foster, J. C., Jr.; Gunger, M. E.; Craig, B. G.; Parsons, G. H.

    1984-08-01

    There are two basic approaches to suppression of sympathetic detonation. Minimizing the shock sensitivity of the explosive to long duration pressure will obviously reduce interround separation distances. However, given that the explosive sensitivity is fixed, then much can be gained through the use of simple barriers placed between the rounds. Researchers devised calculational methods for predicting shock transmission; experimental methods have been developed to characterize explosive shock sensitivity and observe the response of acceptors to barriers. It was shown that both EAK and tritonal can be initiated to detonation with relatively low pressure shocks of long durations. It was also shown that to be an effective barrier between the donor and acceptor, the material must attenuate shock and defect fragments. Future actions will concentrate on refining the design of barriers to minimize weight, volume, and cost.

  6. Reflex Sympathetic Dystrophy in Children

    Directory of Open Access Journals (Sweden)

    Adnan Ayvaz

    2013-10-01

    Full Text Available    Reflex sympathetic dystrophy (chronic regional pain syndrome isn’t frequently encountered in practical pediatrics and childhood. Reflex sympathetic dystrophy syndrome (RSD is a disorder characterized by widespread localized pain, often along with swelling, discoloration, trophic changes and autonomic abnormalities such as vasomotor disorders. Its etio-pathogenesis hasn’t been completely determined.The disease can form in an area innerved by a partially damaged nerve and usually follows minor injury or trauma. In this paper, two girl patients with reflex sympathetic dystrophy are discussed along with the laboratory and clinic finding by accompaniment the literature as it is rarely seen in childhood.

  7. Mediation Analysis of an Adolescent HIV/STI/Pregnancy Prevention Intervention

    Science.gov (United States)

    Glassman, Jill R.; Franks, Heather M.; Baumler, Elizabeth R.; Coyle, Karin K.

    2014-01-01

    Most interventions designed to prevent HIV/STI/pregnancy risk behaviours in young people have multiple components based on psychosocial theories (e.g. social cognitive theory) dictating sets of mediating variables to influence to achieve desired changes in behaviours. Mediation analysis is a method for investigating the extent to which a variable…

  8. iBAT sympathetic innervation is not required for body weight loss induced by central leptin delivery.

    Science.gov (United States)

    Côté, Isabelle; Sakarya, Yasemin; Green, Sara M; Morgan, Drake; Carter, Christy S; Tümer, Nihal; Scarpace, Philip J

    2018-03-01

    We evaluated the contribution of brown adipose tissue (BAT) sympathetic innervation on central leptin-mediated weight loss. In a short- and long-term study, F344BN rats were submitted to either a denervation of interscapular BAT (Denervated) or a sham operation (Sham). Animals from each group received the Ob (Leptin) or green fluorescent protein (GFP; Control) gene through a single injection of recombinant adeno-associated virus delivered centrally. Changes in body weight were recorded for 14 or 35 days, after which adipose tissues and skeletal muscles were weighed. In both studies, hypothalamic phosphorylated STAT3 (P-STAT3) was significantly higher in Sham-Leptin and Denervated-Leptin groups compared with their respective Control groups ( P weight ( P weight loss that stabilized over week 3 of treatment, indicating that sympathetic outflow to BAT is not required for leptin-mediated weight loss. In summary, interscapular BAT (iBAT) denervation did not prevent body weight loss following central leptin gene delivery. The present data show that sympathetic innervation of iBAT is not essential for leptin-induced body weight loss.

  9. [Reflex sympathetic dystrophy].

    Science.gov (United States)

    Oliveira, Marta; Manuela, Manuela; Cantinho, Guilhermina

    2011-01-01

    Reflex Sympathetic Dystrophy is rare in pediatrics. It is a complex regional pain syndrome, of unknown etiology, usually post-traumatic, characterized by dysfunctions of the musculoskeletal, vascular and skin systems: severe persistent pain of a limb, sensory and vascular alterations, associated disability and psychosocial dysfunction. The diagnosis is based in high clinical suspection. In children and adolescents there are aspects that are different from the adult ones. Excessive tests may result in worsening of the clinical symptoms. Bone scintigraphy can help. Pain treatment is difficult, not specific. Physical therapies and relaxation technics give some relief. Depression must be treated. This syndrome includes fibromyalgia and complex regional pain syndrome type I. We present a clinical report of an adolescent girl, referred for pain, cold temperature, pallor and functional disability of an inferior limb, all signals disclosed by a minor trauma. She had been diagnosed depression the year before. The bone scintigraphy was a decisive test. The treatment with gabapentin, C vitamin, physiotherapy and pshycotherapy has been effective.

  10. Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Three Depression Prevention Programs

    Science.gov (United States)

    Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

    2010-01-01

    Objective: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. Method: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB…

  11. A search for activation of C-nociceptors by sympathetic fibers in complex regional pain syndrome

    Science.gov (United States)

    Campero, Mario; Bostock, Hugh; Baumann, Thomas K.; Ochoa, José L.

    2010-01-01

    Objective Although the term ‘reflex sympathetic dystrophy’ has been replaced by ‘complex regional pain syndrome’ (CRPS) type I, there remains a widespread presumption that the sympathetic nervous system is actively involved in mediating chronic neuropathic pain [“sympathetically maintained pain” (SMP)], even in the absence of detectable neuropathophysiology. Methods We have used microneurography to evaluate possible electrophysiological interactions in 24 patients diagnosed with CRPS I (n=13), or CRPS II (n=11) by simultaneously recording from single identified sympathetic efferent fibers and C nociceptors, while provoking sympathetic neural discharges in cutaneous nerves. Results We assessed potential effects of sympathetic activity upon 35 polymodal nociceptors and 19 mechano-insensitive nociceptors, recorded in CRPS I (26 nociceptors) and CRPS II patients (28 nociceptors). No evidence of activation of nociceptors related to sympathetic discharge was found, although nociceptors in 6 CRPS II patients exhibited unrelated spontaneous pathological nerve impulse activity. Conclusion We conclude that activation of nociceptors by sympathetic efferent discharges is not a cardinal pathogenic event in either CRPS I or CRPS II patients. Significance This study shows that sympathetic-nociceptor interactions, if they exist in patients communicating chronic neuropathic pain, must be the exception. PMID:20359942

  12. [Developmental changes of neurotransmitter properties in sympathetic neurons].

    Science.gov (United States)

    Masliukov, P M; Emanuilov, A I; Nozdrachev, A D

    2016-01-01

    Sympathetic ganglia consist of neurochemically and functionally distinct populations of neurons, characterized by a specific projection pattern and a set of neutransmitters including classical mediators (catecholamines and acetylcholine), neuropeptides and small molecules such as NO, H2S, CO. The majority of the principal ganglionic sympathetic neurons is noradrenergic and expresses tyrosine hydroxylase (TH), i.e., a key enzyme in catecholamine synthesis. In mammals, two third of catecholaminergic neurons also co-localizes neuropeptide Y. A small number of ganglionic sympathetic neurons contains enzyme of acetylcholine synthesis and some neuropeptides, such as somatostatin, vasoactive intestinal (poly)peptide (VIP), calcitonin gene-related peptide (CGRP). Acetylcholine-containing sympathetic neurons in most cases colocalize VIP and/or CGRP. Phenotype of autonomic neurons is regulated by both target-independent and target-dependent mechanisms. The most of transmitters are expressed during embryogenesis. TH appears during embryonic development and the percentage of TH-positive neurons remains virtually identical during ontogenesis. After birth, cholinergic neurons exhibit a noradrenergic phenotype. Expression of different neuropeptides changes in pre- and postnatal development. Neurotransmitter expression in sympathetic neurons is influenced by growth factor signaling via innervated target tissues. Multiple growth factors including bone morphogenetic proteins, neurotrophins, glial cell line-derived neurotrophic factor family ligands and neuropoietic cytokines play instructive role at different stages of neurotransmitter development.

  13. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  14. Social mediation of persuasive media in adolescent substance prevention.

    Science.gov (United States)

    Crano, William D; Alvaro, Eusebio M; Tan, Cara N; Siegel, Jason T

    2017-06-01

    Social commentary about prevention messages may affect their likelihood of acceptance. To investigate this possibility, student participants (N = 663) viewed 3 antimarijuana advertisements, each followed immediately by videotaped discussions involving 4 adults or 4 adolescents using either extreme or moderate language in their positive commentaries. The commentaries were expected to affect participants' perceptions of the extent to which the ads were designed to control their behavior (perceived control), which was hypothesized to inhibit persuasion. Two indirect effects analyses were conducted. Marijuana attitudes and usage intentions were the outcome variables. Both analyses revealed statistically significant source by language interactions on participants' perceived control (both p persuasion, and the impact of interpersonal communication variations on acceptance of media-transmitted prevention messages. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Alteration of the Cardiac Sympathetic Innervation Is Modulated by Duration of Diabetes in Female Rats

    Directory of Open Access Journals (Sweden)

    Jitka Švíglerová

    2011-01-01

    Full Text Available To evaluate the sympathetic innervation of the female diabetic heart, resting heart rate and sympathetic tone were assessed in vivo, and effect of tyramine on spontaneous beating rate, norepinephrine atrial concentrations, uptake, and release were determined in vitro in streptozotocin- (STZ- treated rats and respective controls aged 3 months to 2 years. Resting bradycardia, decreased sympathetic tone, deceleration of spontaneous beating rate, and slightly declining carrier-mediated, but preserved exocytotic norepinephrine release from the atria were found in younger diabetic rats while the reactivity of the right atria to tyramine was not affected with age and disease duration. Diabetic two-year-old animals displayed symptoms of partial spontaneous recovery including normoglycemia, increased plasma insulin concentrations, fully recovered sympathetic tone, but putative change, in releasable norepinephrine tissue stores. Our data suggested that female diabetic heart exposed to long-lasting diabetic conditions seems to be more resistant to alteration in sympathetic innervation than the male one.

  16. Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design

    Science.gov (United States)

    Howe, George W.; Beach, Steven R. H.; Brody, Gene H.; Wyman, Peter A.

    2016-01-01

    In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach. PMID:26779062

  17. Translating genetic research into preventive intervention: The baseline target moderated mediator design

    Directory of Open Access Journals (Sweden)

    George W. Howe

    2016-01-01

    Full Text Available In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We end with a discussion of some of the advantages and limitations of this approach.

  18. Antibody-Mediated Rejection: Pathogenesis, Prevention, Treatment, and Outcomes

    Directory of Open Access Journals (Sweden)

    Olivia R. Blume

    2012-01-01

    Full Text Available Antibody-mediated rejection (AMR is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP is effective in removing alloantibodies (DSAs from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.

  19. Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

  20. Evaluating depressive symptom interactions on adolescent smoking prevention program mediators: a mediated moderation analysis.

    Science.gov (United States)

    Sakuma, Kari-Lyn Kobayakawa; Sun, Ping; Unger, Jennifer B; Johnson, C Anderson

    2010-11-01

    Smoking prevention interventions have been shown to be effective in reducing smoking prevalence in the United States. Further work is needed to address smoking in China, where over one third of the world's current smokers reside. China, with more than 60% of the male population being smokers, also presents a unique opportunity to test cognitive processes involved in depression, social influences, and smoking. Adolescents at-risk for developing depression may process social information differently from low-risk counterparts. The Wuhan Smoking Prevention Trial was a school-based longitudinal randomized controlled trial aimed at preventing initiation and escalation of adolescent smoking behaviors. Thousand three hundred and ninety-one male seventh-grade students were assessed with a 200-item paper-and-pencil baseline survey, and it was readministered 1 year later following program implementation. Friend prevalence estimates were significantly higher among 30-day smokers and among those at highest risk for depression symptoms. The program appeared to be successful in changing the perception of friend smoking prevalence only among adolescents with a comorbidity of high scores of depression symptoms and who have experimented previously with smoking. This Program x Comorbidity interaction on perceived friend smoking prevalence was significant in predicting 30-day smoking 1 year after program implementation. This study provides evidence that those adolescents with high levels of depressive symptoms may be more sensitive to social influences associated with smoking prevalence. Individual Disposition x Social Environmental Influences may be important when developing future effective prevention programming.

  1. Sympathetic dysfunction of central origin in patients with ALS

    DEFF Research Database (Denmark)

    Karlsborg, M; Andersen, E B; Wiinberg, N

    2003-01-01

    the centrally and peripherally mediated autonomic vascular reflexes by (i) the local 133-Xenon washout technique, and (ii) the head-up tilt table test. The results correlated to clinical scores. We examined nine ALS patients and 15 age-matched controls. The 133-Xenon washout test showed a significant reduction...... in the centrally mediated sympathetic vasoconstrictor response, but a preserved locally mediated response in the patients. In the head-up tilt table test, the patients had a significantly higher mean arterial blood pressure (MAP) compared with controls, probably due to a general increase in vascular resistance...

  2. Directed microspore-specific recombination of transgenic alleles to prevent pollen-mediated transmission of transgenes

    NARCIS (Netherlands)

    Mlynarova, L.; Conner, A.J.; Nap, J.P.H.

    2006-01-01

    A major challenge for future genetically modified (GM) crops is to prevent undesired gene flow of transgenes to plant material intended for another use. Recombinase-mediated auto excision of transgenes directed by a tightly controlled microspore-specific promoter allows efficient removal of either

  3. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons.

    Science.gov (United States)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stéphanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    2010-07-01

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade to prevent/cure this rejection. Here, we used a baboon model of preimmunization to explore the prevention of acute antibody-mediated rejection by an early inhibition of the classical complement pathway using human recombinant C1-inhibitor. Baboons were immunized against peripheral blood mononuclear cells from allogeneic donors and, once a specific and stable immunization had been established, they received a kidney from the same donor. Rejection occurred at day 2 posttransplant in untreated presensitized recipients, with characteristic histological lesions and complement deposition. As recombinant human C1-inhibitor blocks in vitro cytotoxicity induced by donor-specific antibodies, other alloimmunized baboons received the drug thrice daily intravenously during the first 5 days after transplant. Rejection was prevented during this treatment but occurred after discontinuation of treatment. We show here that early blockade of complement activation by recombinant human C1-inhibitor can prevent acute antibody-mediated rejection in presensitized recipients. This treatment could also be useful in other forms of acute antibody-mediated rejection caused by induced antibodies.

  4. Preventing and De-Escalating Ethical Conflict: A Communication-Training Mediation Model.

    Science.gov (United States)

    Levin, Tomer T; Parker, Patricia A

    2015-01-01

    While ethical conflicts in the provision of healthcare are common, the current third-party mediator model is limited by a lack of expert ethical mediators, who are often not on site when conflict escalates. In order to improve clinical outcomes in situations such as conflicts at the end of life, we suggest that clinicians-physicians, nurses and social workers-be trained to prevent and de-escalate emerging conflicts. This can be achieved using a mediation model framed by a communication-training approach. A case example is presented and the model is discussed. The implication of this preventative/early intervention model for improving clinical outcomes, in particular end-of life conflict, is considered. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  5. The Effect of Technology-Mediated Diabetes Prevention Interventions on Weight: A Meta-Analysis.

    Science.gov (United States)

    Bian, Rachel R; Piatt, Gretchen A; Sen, Ananda; Plegue, Melissa A; De Michele, Mariana L; Hafez, Dina; Czuhajewski, Christina M; Buis, Lorraine R; Kaufman, Neal; Richardson, Caroline R

    2017-03-27

    Lifestyle interventions targeting weight loss, such as those delivered through the Diabetes Prevention Program, reduce the risk of developing type 2 diabetes. Technology-mediated interventions may be an option to help overcome barriers to program delivery, and to disseminate diabetes prevention programs on a larger scale. We conducted a meta-analysis to evaluate the effect of such technology-mediated interventions on weight loss. In this meta-analysis, six databases were searched to identify studies reporting weight change that used technology to mediate diet and exercise interventions, and targeted individuals at high risk for developing type 2 diabetes. Studies published between January 1, 2002 and August 4, 2016 were included. The search identified 1196 citations. Of those, 15 studies met the inclusion criteria and evaluated 18 technology-mediated intervention arms delivered to a total of 2774 participants. Study duration ranged from 12 weeks to 2 years. A random-effects meta-analysis showed a pooled weight loss effect of 3.76 kilograms (95% CI 2.8-4.7; Ptechnology-mediated intervention method was most efficacious. Technology-mediated diabetes prevention programs can result in clinically significant amounts of weight loss, as well as improvements in glycaemia in patients with prediabetes. Due to their potential for large-scale implementation, these interventions will play an important role in the dissemination of diabetes prevention programs. ©Rachel R Bian, Gretchen A Piatt, Ananda Sen, Melissa A Plegue, Mariana L De Michele, Dina Hafez, Christina M Czuhajewski, Lorraine R Buis, Neal Kaufman, Caroline R Richardson. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.03.2017.

  6. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. (Indiana Univ. School of Medicine, IN (USA))

    1989-11-15

    Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

  7. Advances in sympathetic nerve recording in humans

    Directory of Open Access Journals (Sweden)

    Elisabeth eLambert

    2012-02-01

    Full Text Available Sympathetic nerve recording is commonly assessed by measuring the firing activity of a number of neurones. While the estimation of overall sympathetic nervous activity using this multiunit recording approach has advanced our understanding of sympathetic regulation in health and disease no information is gained regarding the underling mechanisms generating the bursts of sympathetic activity. The introduction of single-unit recording has been a major step forward, enabling the examination of specific sympathetic firing patterns in diverse clinical conditions. Disturbances in sympathetic nerve firing, including high firing probabilities, high firing rates or high incidence of multiple firing, or a combination of both, may have clinical implications with regards to the development and progression of target organ damage. Understanding the mechanisms and consequences of specific firing patterns would permit the development of therapeutic strategies targeting these nuances of sympathetic overdrive.

  8. Functional imaging of sympathetic activation during mental stress.

    Science.gov (United States)

    Fechir, M; Gamer, M; Blasius, I; Bauermann, T; Breimhorst, M; Schlindwein, P; Schlereth, T; Birklein, F

    2010-04-01

    Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin conductance and heart rate were continuously recorded. The results show that sympathetic activation through mental stress is associated with distinct cerebral regions being immediately involved in task performance (visual, motor, and premotor areas). Other activated regions (right insula, dorsolateral superior frontal gyrus, cerebellar regions) are unrelated to task performance. These latter regions have previously been considered to be involved in mediating different stress responses. The results might furthermore serve as a basis for future investigations of the connection between these cortical regions in the generation of stress-related diseases. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Interrupting violence: how the CeaseFire Program prevents imminent gun violence through conflict mediation.

    Science.gov (United States)

    Whitehill, Jennifer M; Webster, Daniel W; Frattaroli, Shannon; Parker, Elizabeth M

    2014-02-01

    Cities are increasingly adopting CeaseFire, an evidence-based public health program that uses specialized outreach workers, called violence interrupters (VIs), to mediate potentially violent conflicts before they lead to a shooting. Prior research has linked conflict mediation with program-related reductions in homicides, but the specific conflict mediation practices used by effective programs to prevent imminent gun violence have not been identified. We conducted case studies of CeaseFire programs in two inner cities using qualitative data from focus groups with 24 VIs and interviews with eight program managers. Study sites were purposively sampled to represent programs with more than 1 year of implementation and evidence of program effectiveness. Staff with more than 6 months of job experience were recruited for participation. Successful mediation efforts were built on trust and respect between VIs and the community, especially high-risk individuals. In conflict mediation, immediate priorities included separating the potential shooter from the intended victim and from peers who may encourage violence, followed by persuading the parties to resolve the conflict peacefully. Tactics for brokering peace included arranging the return of stolen property and emphasizing negative consequences of violence such as jail, death, or increased police attention. Utilizing these approaches, VIs are capable of preventing gun violence and interrupting cycles of retaliation.

  10. Reasons for Testing Mediation in the Absence of an Intervention Effect: A Research Imperative in Prevention and Intervention Research.

    Science.gov (United States)

    O'Rourke, Holly P; MacKinnon, David P

    2018-03-01

    Mediation models are used in prevention and intervention research to assess the mechanisms by which interventions influence outcomes. However, researchers may not investigate mediators in the absence of intervention effects on the primary outcome variable. There is emerging evidence that in some situations, tests of mediated effects can be statistically significant when the total intervention effect is not statistically significant. In addition, there are important conceptual and practical reasons for investigating mediation when the intervention effect is nonsignificant. This article discusses the conditions under which mediation may be present when an intervention effect does not have a statistically significant effect and why mediation should always be considered important. Mediation may be present in the following conditions: when the total and mediated effects are equal in value, when the mediated and direct effects have opposing signs, when mediated effects are equal across single and multiple-mediator models, and when specific mediated effects have opposing signs. Mediation should be conducted in every study because it provides the opportunity to test known and replicable mediators, to use mediators as an intervention manipulation check, and to address action and conceptual theory in intervention models. Mediators are central to intervention programs, and mediators should be investigated for the valuable information they provide about the success or failure of interventions.

  11. Street conflict mediation to prevent youth violence: conflict characteristics and outcomes.

    Science.gov (United States)

    Whitehill, Jennifer M; Webster, Daniel W; Vernick, Jon S

    2013-06-01

    Mediation of potentially violent conflicts is a key component of CeaseFire, an effective gun violence-prevention programme. To describe conflicts mediated by outreach workers (OW) in Baltimore's CeaseFire replication, examine neighbourhood variation, and measure associations between conflict risk factors and successful nonviolent resolution. A cross-sectional study was conducted using records for 158 conflicts mediated between 2007 and 2009. Involvement of youth, gangs, retaliation, weapons and other risk factors were described. Principal component analysis (PCA) was used for data-reduction purposes before the relationship between conflict risk components and mediation success was assessed with multivariate logistic regression. Most conflicts involved 2-3 individuals. Youth, persons with a history of violence, gang members and weapons were commonly present. OWs reported immediate, nonviolent resolution for 65% of mediated conflicts; an additional 23% were at least temporarily resolved without violence. PCA identified four dimensions of conflict risk: the risk-level of individuals involved; whether the incident was related to retaliation; the number of people involved; and shooting likelihood. However, these factors were not related to the OW's ability to resolve the conflict. Neighbourhoods with programme-associated reductions in homicides mediated more gang-related conflicts; neighbourhoods without programme-related homicide reductions encountered more retaliatory conflicts and more weapons.

  12. The mediation as an apt tool for the prevention of crime as result of gender violence

    OpenAIRE

    Yaíma Águila Gutiérrez; Marileydis Pino Rosa

    2017-01-01

    Violence based in gender is an actual, social, historical and cultural matter. It affects to million persons around the world in the personal, familiar and social ambit. Violence based in gender could damage relationships and also could become in a crime. Mediation is an apt tool to use before the intervention of law for solving gender violence´s conflicts which could need the intervention of criminal law. Those reasons show that is necessary the prevention of gender violence so is important ...

  13. A case of linear morphoea mistaken for reflex sympathetic dystrophy.

    Science.gov (United States)

    Thng, Steven Tien Guan; Wong, Keryi

    2013-03-01

    Morphoea, or localised scleroderma, is a disease entity with poorly understood pathogenesis. Early diagnosis of the condition is crucial in order to prevent permanent morbidity. However, initial presentations of morphoea can be nonspecific and easily mistaken for other conditions, resulting in late treatment and permanent disability. We report a case of linear morphoea in a 22-year-old man who was initially diagnosed with reflex sympathetic dystrophy. By the time the diagnosis of morphoea was confirmed, the patient had already developed contractures.

  14. [Reflex sympathetic dystrophy of childhood: one case].

    Science.gov (United States)

    Jouary, T; Boralevi, F; Pillet, P; Taieb, A; Léauté-Labrèze, C

    2002-10-01

    Reflex sympathetic dystrophy (Complex Regional Pain Syndrome type 1) is little known by dermatologists. We report a pediatric case of reflex sympathetic dystrophy with predominant cutaneous involvement. A 10 year-old girl presented a warm, painful and relapsing right hand edema for seven months (three outbreaks). The hand was cyanotic, pigmented and painful. Routine blood tests were normal. Radiography and radionuclide bone scan were consistent with stage 1 reflex sympathetic dystrophy. Physiotherapy led to dramatic improvement. Reflex sympathetic dystrophy is known since the XVIIIth century. In the last decade, progress in radiology and bone scan have provided elements for understanding the physiopathology of the disease. Microvascular abnormalities under the control of sympathetic nervous system are characteristic of different stages of reflex sympathetic dystrophy. Recently, neurovascular system experiments showed that sympathetic reflex tonus changes may be controlled by the central nervous system. Dermatologic changes of reflex sympathetic dystrophy are well known: edema and erythema in first stage, cyanosis in second stage, sclerosis and atrophia in third stage, but pediatric cases are rarely reported. Reflex sympathetic dystrophy is a complex disease, however its physiopathology is now understood. The clinical presentation can be atypical and the dermatologist may be the first to be consulted.

  15. Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation.

    Science.gov (United States)

    Lawrence, Helen; Mawdesley, Amy Elizabeth; Holland, James Patrick; Kirby, John Andrew; Deehan, David John; Tyson-Capper, Alison Jane

    2016-02-16

    Cobalt-chrome alloy is a widely used biomaterial in joint replacements, dental implants and spinal rods. Although it is an effective and biocompatible material, adverse reactions to metal debris (ARMD) have arisen in a minority of patients, particularly in those with metal-on-metal bearing hip replacements. There is currently no treatment for ARMD and once progressive, early revision surgery of the implant is necessary. Therapeutic agents to prevent, halt or reverse ARMD would therefore be advantageous. Cobalt ions activate Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to bacterial lipopolysaccharide (LPS) resulting in the production of pro-inflammatory cytokines and chemokines. We hypothesised that anti-TLR4 neutralising antibodies, reported to inhibit TLR4-mediated inflammation, could prevent the inflammatory response to cobalt ions in an in vitro macrophage cell culture model. This study shows that a monoclonal anti-TLR4 antibody inhibited cobalt-mediated increases in pro-inflammatory IL8, CCL20 and IL1A expression, as well as IL-8 secretion. In contrast, a polyclonal antibody did not prevent the effect of cobalt ions on either IL-8 or IL1A expression, although it did have a small effect on the CCL20 response. Interestingly, both antibodies inhibited cobalt-mediated neutrophil migration although the greater effect was observed with the monoclonal antibody. In summary our data shows that a monoclonal anti-TLR4 antibody can inhibit cobalt-mediated inflammatory responses while a polyclonal antibody only inhibits the effect of specific cytokines. Anti-TLR4 antibodies have therapeutic potential in ARMD although careful antibody design is required to ensure that the LPS response is preserved.

  16. Sympathetic actions on the skeletal muscle.

    Science.gov (United States)

    Roatta, Silvestro; Farina, Dario

    2010-01-01

    The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

  17. [ Sudeck's bone atrophy (reflex sympathetic dystrophy)].

    Science.gov (United States)

    Hayashi, Yasufumi

    2008-07-01

    Reflex sympathetic dystrophy is a disease clinically characterized severe pain, allodynia (severe pain caused by a touch) and over-reaction of pain sensation after a minor injury. In 1994, reflex sympathetic dystrophy was given a name of complex regional pain syndrome type 1 by a international congress, because local blockade of the sympathetic nerve has not been found to be invariably effective. Treatment system for reflex sympathetic dystrophy is composed of medicament therapy including oral administration and/or injection of drug, physical therapy such as thermotherapy and gently passive movement, surgical treatment and psychotherapy. Treatment with injection of pamidronate for 23 patients with reflex sympathetic dystrophy revealed to reduced the grade of pain to two third compared to pre-treatment period, and local intravenous block with local anesthetic drug and steroid hormone disappeared the almost symptoms in cases of early phase.

  18. The mediation as an apt tool for the prevention of crime as result of gender violence

    Directory of Open Access Journals (Sweden)

    Yaíma Águila Gutiérrez

    2017-07-01

    Full Text Available Violence based in gender is an actual, social, historical and cultural matter. It affects to million persons around the world in the personal, familiar and social ambit. Violence based in gender could damage relationships and also could become in a crime. Mediation is an apt tool to use before the intervention of law for solving gender violence´s conflicts which could need the intervention of criminal law. Those reasons show that is necessary the prevention of gender violence so is important the intervention of criminology.

  19. Numerical modeling of sympathetic detonation

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, A.L.; Kershner, J.D.; Mader, C.L.

    1979-11-01

    The sympathetic detonation of small cubes of solid rocket propellant was modeled numerically, using the Eulerian reactive hydrodynamic code 2DE with Forest Fire burn rates. The model was applied to cubes of 1 to 3 in., with excellent agreement between calculated and experimental results. The model also was applied to several propellants and to different experimental arrangements. The blast-wave pressures in the air gap and the induced shock pressures in the acceptor were obtained from the model. The correlation between these pressures was coupled with a study of the effect of the length-to-diameter ratio of a donor cylinder and the necessary conditions for detonation of the acceptor to provide a semiquantitative predictive capability.

  20. Moderators and mediators of outcome in Internet-based indicated prevention for eating disorders.

    Science.gov (United States)

    Völker, Ulrike; Jacobi, Corinna; Trockel, Mickey T; Taylor, C Barr

    2014-12-01

    The objective of this study was to investigate moderators and mediators of the effect of an indicated prevention program for eating disorders (ED) on reduction of dysfunctional attitudes and specific ED symptoms. 126 women (M age = 22.3; range 18-33) reporting subthreshold ED symptoms were randomized to the Student Bodies™+ (SB+) intervention or an assessment-only control condition. Assessments took place at pre-intervention, mid-intervention (mediators), post-intervention, and 6-month follow-up. Mixed effects modeling including all available data from all time points were used for the data analysis. Intervention effects on the reduction of binge rate were weaker for participants with higher baseline BMI and for participants with a lower baseline purge rate. Intervention effects on reduction of eating disorder pathology were weaker for participants with higher baseline purge rate and with initial restrictive eating. No moderators of the intervention effect on restrictive eating were identified. An increase in knowledge mediated the beneficial effect of SB+ on binge rate. The results suggest that different moderators should be considered for the reduction of symptoms and change in attitudes of disturbed eating and that SB+ at least partially operates through psychoeducation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Central SDF-1/CXCL12 expression and its cardiovascular and sympathetic effects: the role of angiotensin II, TNF-α, and MAP kinase signaling

    Science.gov (United States)

    Wei, Shun-Guang; Zhang, Zhi-Hua; Yu, Yang

    2014-01-01

    The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptors are expressed by neurons and glial cells in cardiovascular autonomic regions of the brain, including the hypothalamic paraventricular nucleus (PVN), and contribute to neurohumoral excitation in rats with ischemia-induced heart failure. The present study examined factors regulating the expression of SDF-1 in the PVN and mechanisms mediating its sympatho-excitatory effects. In urethane anesthetized rats, a 4-h intracerebroventricular (ICV) infusion of angiotensin II (ANG II) or tumor necrosis factor-α (TNF-α) in doses that increase mean blood pressure (MBP) and sympathetic drive increased the expression of SDF-1 in PVN. ICV administration of SDF-1 increased the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK), JNK, and p38 MAPK in PVN, along with MBP, heart rate (HR), and renal sympathetic nerve activity (RSNA), but did not affect total p44/42 MAPK, JNK, and p38 MAPK levels. ICV pretreatment with the selective p44/42 MAPK inhibitor PD98059 prevented the SDF-1-induced increases in MBP, HR, and RSNA; ICV pretreatment with the selective JNK and p38 MAPK inhibitors attenuated but did not block these SDF-1-induced excitatory responses. ICV PD98059 also prevented the sympatho-excitatory response to bilateral PVN microinjections of SDF-1. ICV pretreatment with SDF-1 short-hairpin RNA significantly reduced ANG II- and TNF-α-induced phosphorylation of p44/42 MAPK in PVN. These findings identify TNF-α and ANG II as drivers of SDF-1 expression in PVN and suggest that the full expression of their cardiovascular and sympathetic effects depends upon SDF-1-mediated activation of p44/42 MAPK signaling. PMID:25260613

  2. Paroxysmal sympathetic hyperactivity: An entity to keep in mind.

    Science.gov (United States)

    Godoy, D A; Panhke, P; Guerrero Suarez, P D; Murillo-Cabezas, F

    2017-12-15

    Paroxysmal sympathetic hyperactivity (PSH) is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries. It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge. The diagnosis is based on the clinical findings, and high alert rates are required. No widely available and validated homogeneous diagnostic criteria have been established to date. There have been recent consensus attempts to shed light on this obscure phenomenon. Its physiopathology is complex and has not been fully clarified. However, the excitation-inhibition model is the theory that best explains the different aspects of this condition, including the response to treatment with the available drugs. The key therapeutic references are the early recognition of the disorder, avoiding secondary injuries and the triggering of paroxysms. Once sympathetic crises occur, they must peremptorily aborted and prevented. of the later the syndrome is recognized, the poorer the patient outcome. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  3. High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure

    NARCIS (Netherlands)

    Gomes, M.E.R.; El Messaoudi, S.; Lenders, J.W.M.; Bellersen, L.; Verheugt, F.W.A.; Smits, P.; Tack, C.J.J.

    2011-01-01

    WHAT IS KNOWN AND OBJECTIVE: The increased central sympathetic activity typically associated with chronic heart failure (CHF) is probably mediated by formation of reactive oxygen species (ROS) in the brain. Our objective was to undertake a trial to test our hypothesis that administration of the

  4. Superoxide anions in paraventricular nucleus modulate adipose afferent reflex and sympathetic activity in rats.

    Directory of Open Access Journals (Sweden)

    Lei Ding

    Full Text Available Adipose afferent reflex (AAR is a sympatho-excitatory reflex induced by chemical stimulation of white adipose tissue (WAT. Ionotropic glutamate receptors including NMDA receptors (NMDAR and non-NMDA receptors (non-NMDAR in paraventricular nucleus (PVN mediate the AAR. Enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate the role and mechanism of superoxide anions in PVN in modulating the AAR.Renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injections of capsaicin into four sites of right inguinal WAT (8.0 nmol in 8.0 µl for each site. Microinjection of polyethylene glycol-superoxide dismutase (PEG-SOD, the superoxide anion scavenger tempol or the NAD(PH oxidase inhibitor apocynin into the PVN decreased the baseline RSNA and MAP, and attenuated the AAR. Unilateral WAT injection of capsaicin increased superoxide anions in bilateral PVN, which was prevented by the WAT denervation. WAT injection of capsaicin increased superoxide anion level and NAD(PH oxidase activity in the PVN, which was abolished by the PVN pretreatment with the combined NMDAR antagonist AP5 and non-NMDAR antagonist CNQX. Microinjection of the NMDAR agonist NMDA or the non-NMDAR agonist AMPA increased superoxide anion level and NAD(PH oxidase activity in the PVN.NAD(PH oxidase-derived superoxide anions in the PVN contributes to the tonic modulation of AAR. Activation of ionotropic glutamate receptors in the PVN is involved in the AAR-induced production of superoxide anions in the PVN.

  5. Sympathetic Cooling of Trapped Cd+ Isotopes

    OpenAIRE

    Blinov, B. B.; Deslauriers, L.; Lee, P.; Madsen, M. J.; Miller, R.; Monroe, C.

    2001-01-01

    We sympathetically cool a trapped 112Cd+ ion by directly Doppler-cooling a 114Cd+ ion in the same trap. This is the first demonstration of optically addressing a single trapped ion being sympathetically cooled by a different species ion. Notably, the experiment uses a single laser source, and does not require strong focusing. This paves the way toward reducing decoherence in an ion trap quantum computer based on Cd+ isotopes.

  6. Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice.

    Science.gov (United States)

    Draibe, Juliana; Pepper, Ruth J; Salama, Alan D

    Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previously demonstrated protection from glomerular disease in S100A9-deficient mice. The aim of this study was to assess the efficacy of paquinimod in the prevention and treatment of experimental glomerulonephritis. Nephrotoxic nephritis (NTN) was induced in C57BL/6 mice according to our standard protocol. Mice were treated with different doses of paquinimod either at disease induction (prevention group) or two days following induction (therapeutic group) and sacrificed 8 days following induction. Disease was assessed histologically (number of glomerular crescents, degree of glomerular thrombosis, number of infiltrating leucocytes and calprotectin expression) and biochemically (serum creatinine and urea levels, and urinary levels of protein). Neither treatment with low (0.5mg/kg) or high (25mg/kg) doses of paquinimod, given preventatively or therapeutically, led to disease attenuation, as assessed by biochemical or histological parameters. Additionally, we found trends for an increase in renal glomerular calprotectin expression in the high dose groups, suggesting a possible feedback regulation of calprotectin expression. Our results show that paquinimod does not successfully prevent or treat mice with NTN. Other models of immune-mediated glomerulonephritis need to be tested to investigate the therapeutic potential of this compound in renal disease. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Morbidity in reflex sympathetic dystrophy

    Science.gov (United States)

    Murray, C.; Cohen, A.; Perkins, T.; Davidson, J.; Sills, J.

    2000-01-01

    Reflex sympathetic dystrophy (RSD), an unusual diagnosis in general paediatrics, is well recognised by paediatric rheumatologists. This study reports the presentation and the clinical course of 46 patients (35 female, age range 8-15.2) with RSD. The patients saw professionals from an average of 2.3 specialties (range 1-5). Twenty five (54%) had a history of trauma. Median time to diagnosis was 12 weeks (range 1-130). Many children had multiple investigations and treatments. Once diagnosis was made, treatment followed with physiotherapy and analgesics. Median time to recovery was seven weeks (range 1-140), with 27.5% relapsing. Nine children required assessment by the child and adolescent psychiatry team. This disease, though rare, has significant morbidity and it is therefore important to raise clinicians' awareness of RSD in childhood. Children with the condition may then be recognised and referred for appropriate management earlier, and spared unnecessary investigations and treatments which may exacerbate the condition.

 PMID:10685927

  8. Olanzapine-induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin.

    Science.gov (United States)

    Romo-Nava, Francisco; Buijs, Frederik N; Valdés-Tovar, Marcela; Benítez-King, Gloria; Basualdo, MariCarmen; Perusquía, Mercedes; Heinze, Gerhard; Escobar, Carolina; Buijs, Ruud M

    2017-05-01

    Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine-induced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3β, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation. © 2017

  9. Angiotensin-(1-7 in Paraventricular Nucleus Contributes to the Enhanced Cardiac Sympathetic Afferent Reflex and Sympathetic Activity in Chronic Heart Failure Rats

    Directory of Open Access Journals (Sweden)

    Xingsheng Ren

    2017-08-01

    Full Text Available Background/Aims: Cardiac sympathetic afferent reflex (CSAR enhancement contributes to exaggerated sympathetic activation in chronic heart failure (CHF. The current study aimed to investigate the roles of angiotensin (Ang-(1-7 in CSAR modulation and sympathetic activation and Ang-(1-7 signaling pathway in paraventricular nucleus of CHF rats. Methods: CHF was induced by coronary artery ligation. Responses of renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP to epicardial application of capsaicin were used to evaluate CSAR in rats with anesthesia. Results: Ang-(1-7 increased RSNA, MAP, CSAR activity, cAMP level, NAD(PH oxidase activity and superoxide anion level more significantly in CHF than in sham-operated rats, while Mas receptor antagonist A-779 had the opposite effects. Moreover, Ang-(1-7 augmented effects of Ang II in CHF rats. The effects of Ang-(1-7 were blocked by A-779, adenylyl cyclase inhibitor SQ22536, protein kinase A inhibitor Rp-cAMP, superoxide anion scavenger tempol and NAD(PH oxidase inhibitor apocynin. Mas and AT1 receptor protein expressions, Ang-(1-7 and Ang II levels in CHF increased. Conclusions: These results indicate that Ang-(1-7 in paraventricular nucleus enhances CSAR and sympathetic output not only by exerting its own effects but also by augmenting the effects of Ang II through Mas receptor in CHF. Endogenous Ang-(1-7/Mas receptor activity contributes to CSAR enhancement and sympathetic activation in CHF, and NAD(PH oxidase-derived superoxide anions and the cAMP-PKA signaling pathway are involved in mediating the effects of Ang-(1-7 in CHF.

  10. Sympathetic baroreflex gain in normotensive pregnant women.

    Science.gov (United States)

    Usselman, Charlotte W; Skow, Rachel J; Matenchuk, Brittany A; Chari, Radha S; Julian, Colleen G; Stickland, Michael K; Davenport, Margie H; Steinback, Craig D

    2015-09-01

    Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism. Copyright © 2015 the American Physiological Society.

  11. Exercise prevents age-related decline in nitric-oxide-mediated vasodilator function in cutaneous microvessels.

    Science.gov (United States)

    Black, Mark A; Green, Daniel J; Cable, N Timothy

    2008-07-15

    Ageing is associated with impaired endothelium-derived nitric oxide (NO) function in human microvessels. We investigated the impact of cardiorespiratory fitness and exercise training on physiological and pharmacological NO-mediated microvascular responses in older subjects. NO-mediated vasodilatation was examined in young, older sedentary and older fit subjects who had two microdialysis fibres embedded into the skin on the ventral aspect of the forearm and laser Doppler probes placed over these sites. Both sites were then heated to 42 degrees C, with Ringer solution infused in one probe and N-nitro-L-arginine methyl ester (L-NAME) through the second. In another study, three doses of ACh were infused in the presence or absence of L-NAME in similar subjects. The older sedentary subjects then undertook exercise training, with repeat studies at 12 and 24 weeks. The NO component of the heat-induced rise in cutaneous vascular conductance (CVC) was diminished in the older sedentary subjects after 30 min of prolonged heating at 42 degrees C (26.9 +/- 3.9%CVC(max)), compared to older fit (46.2 +/- 7.0%CVC(max), P incremental heating (P < 0.05). Similarly, the NO contribution to ACh responses was impaired in the older sedentary versus older fit subjects (low dose 3.2 +/- 1.3 versus 6.6 +/- 1.3%CVC(max); mid dose 11.4 +/- 2.4 versus 21.6 +/- 4.5%CVC(max); high dose 35.2 +/- 6.0 versus 52.6 +/- 7.9%CVC(max), P < 0.05) and training reversed this (12 weeks: 13.7 +/- 3.6, 28.9 +/- 5.3, 56.1 +/- 3.9%CVC(max), P < 0.05). These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents age-related decline in indices of physiological and pharmacological microvascular NO-mediated vasodilator function. Since higher levels of NO confer anti-atherogenic benefit, this study has potential implications for the prevention of microvascular dysfunction in humans.

  12. Environmental Enrichment Potently Prevents Microglia-Mediated Neuroinflammation by Human Amyloid β-Protein Oligomers.

    Science.gov (United States)

    Xu, Huixin; Gelyana, Eilrayna; Rajsombath, Molly; Yang, Ting; Li, Shaomin; Selkoe, Dennis

    2016-08-31

    Microglial dysfunction is increasingly recognized as a key contributor to the pathogenesis of Alzheimer's disease (AD). Environmental enrichment (EE) is well documented to enhance neuronal form and function, but almost nothing is known about whether and how it alters the brain's innate immune system. Here we found that prolonged exposure of naive wild-type mice to EE significantly altered microglial density and branching complexity in the dentate gyrus of hippocampus. In wild-type mice injected intraventricularly with soluble Aβ oligomers (oAβ) from hAPP-expressing cultured cells, EE prevented several morphological features of microglial inflammation and consistently prevented oAβ-mediated mRNA changes in multiple inflammatory genes both in vivo and in primary microglia cultured from the mice. Microdialysis in behaving mice confirmed that EE normalized increases in the extracellular levels of the key cytokines (CCL3, CCL4, TNFα) identified by the mRNA analysis. Moreover, EE prevented the changes in microglial gene expression caused by ventricular injection of oAβ extracted directly from AD cerebral cortex. We conclude that EE potently alters the form and function of microglia in a way that prevents their inflammatory response to human oAβ, suggesting that prolonged environmental enrichment could protect against AD by modulating the brain's innate immune system. Environmental enrichment (EE) is a potential therapy to delay Alzheimer's disease (AD). Microglial inflammation is associated with the progression of AD, but the influence of EE on microglial inflammation is unclear. Here we systematically applied in vivo methods to show that EE alters microglia in the dentate gyrus under physiological conditions and robustly prevents microglial inflammation induced by human Aβ oligomers, as shown by neutralized microglial inflammatory morphology, mRNA changes, and brain interstitial fluid cytokine levels. Our findings suggest that EE alters the innate immune system

  13. The Reflex Sympathetic Dystrophy Syndrome: A Review with Special Reference to Chronic Pain and Motor Impairments.

    Science.gov (United States)

    Ribbers, G.; And Others

    1995-01-01

    This article reviews reflex sympathetic dystrophy (RSD), a symptom complex caused by a minor injury and characterized by pain, vasomotor and trophic disregulation, and motor impairments. Both an acute stage and a chronic stage are described. Implications for diagnosis, prevention of disabilities, and development of rehabilitation strategies are…

  14. Reflex sympathetic dystrophy syndrome and neuromediators.

    Science.gov (United States)

    Pham, Thao; Lafforgue, Pierre

    2003-02-01

    Concepts related to the pathophysiology of reflex sympathetic dystrophy syndrome (RSDS) are changing. Although sympathetic influences are still viewed as the most likely mechanism underlying the development and/or perpetuation of RSDS, these influences are no longer ascribed to an increase in sympathetic tone. Rather, the most likely mechanism may be increased sensitivity to catecholamines due to sympathetic denervation with an increase in the number and/or sensitivity of peripheral axonal adrenoceptors. Several other pathophysiological mechanisms have been suggested, including neurogenic inflammation with the release of neuropeptides by primary nociceptive afferents and sympathetic efferents. These neuromediators, particularly substance P, calcitonin gene-related peptide, and neuropeptide Y (NPY), may play a pivotal role in the genesis of pain in RSDS. They induce an inflammatory response (cutaneous erythema and edema) and lower the pain threshold. Neurogenic inflammation at the site of the lesion with neuromediator accumulation or depletion probably contributes to the pathophysiology of RSDS. However, no single neuromediator has been proved responsible, and other hypotheses continue to arouse interest.

  15. Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

    Directory of Open Access Journals (Sweden)

    Clara Quintas

    2018-05-01

    Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

  16. Prevention of behavior problems for children in foster care: outcomes and mediation effects.

    Science.gov (United States)

    Chamberlain, Patricia; Price, Joe; Leve, Leslie D; Laurent, Heidemarie; Landsverk, John A; Reid, John B

    2008-03-01

    Parent training for foster parents is mandated by federal law and supported by state statues in nearly all states; however, little is known about the efficacy of that training, and recent reviews underscore that the most widely used curricula in the child welfare system (CWS) have virtually no empirical support (Grimm, Youth Law News, April-June:3-29, 2003). On the other hand, numerous theoretically based, developmentally sensitive parent training interventions have been found to be effective in experimental clinical and prevention intervention trials (e.g., Kazdin and Wassell, Journal of the American Academy of Child and Adolescent Psychiatry, 39:414-420, 2000; McMahon and Forehand, Helping the noncompliant child, Guilford Press, New York, USA, 2003; Patterson and Forgatch, Parents and adolescents: I. Living together, Castalia Publishing, Eugene, OR, USA, 1987; Webster-Stratton et al., Journal of Clinical Child Pyschology Psychiatry, 42:943-952, 2001). One of these, Multidimensional Treatment Foster Care (MTFC; Chamberlain, Treating chronic juvenile offenders: Advances made through the Oregon Multidimensional Treatment Foster Care model, American Psychological Association, Washington, DC, USA, 2003), has been used with foster parents of youth referred from juvenile justice. The effectiveness of a universal intervention, KEEP (Keeping Foster Parents Trained and Supported) based on MTFC (but less intensive) was tested in a universal randomized trial with 700 foster and kinship parents in the San Diego County CWS. The goal of the intervention was to reduce child problem behaviors through strengthening foster parents' skills. The trial was designed to examine effects on both child behavior and parenting practices, allowing for specific assessment of the extent to which improvements in child behavior were mediated by the parenting practices targeted in the intervention. Child behavior problems were reduced significantly more in the intervention condition than in the

  17. Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Two Eating Disorder Prevention Programs

    Science.gov (United States)

    Stice, Eric; Presnell, Katherine; Gau, Jeff; Shaw, Heather

    2007-01-01

    The authors investigated mediators hypothesized to account for the effects of 2 eating disorder prevention programs using data from 355 adolescent girls who were randomized to a dissonance or a healthy weight intervention or an active control condition. The dissonance intervention produced significant reductions in outcomes (body…

  18. HEAT SHOCK FACTOR 1-MEDIATED THERMOTOLERANCE PREVENTS CELL DEATH AND RESULTS IN G2/M CELL CYCLE ARREST

    Science.gov (United States)

    Mammalian cells respond to stress by activating heat shock transcription factors (e.g., HSF1) that regulate increased synthesis of heat shock proteins (HSPs). HSPs mediate protection from deleterious effects of stress by preventing permanent disruption of normal cellular mitosis...

  19. Phosphoproteome profiling provides insight into the mechanism of action for carvedilol-mediated cancer prevention.

    Science.gov (United States)

    Cleveland, Kristan H; Yeung, Steven; Huang, Kevin M; Liang, Sherry; Andresen, Bradley T; Huang, Ying

    2018-04-06

    Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways. The array data indicated that both EGF and carvedilol increased phosphorylation of ERK's cytosolic target P70S6K while its nuclear target ELK-1 were activated only by EGF; Furthermore, EGF-induced phosphorylation of ELK-1 and c-Jun was attenuated by carvedilol. Subcellular fractionation analysis indicated that ERK nuclear translocation induced by EGF was blocked by co-treatment with carvedilol. Western blot and luciferase reporter assays confirmed that the biased β-blockers carvedilol and alprenolol blocked EGF-induced phosphorylation and activation of c-Jun/AP-1 and ELK-1. Consistently, both carvedilol and alprenolol strongly prevented EGF-induced neoplastic transformation of JB6 P+ cells. Remarkably, oral carvedilol treatment significantly inhibited the growth of A375 melanoma xenograft in SCID mice. Since nuclear translocation of ERK is a key step in carcinogenesis, inhibition of this event is proposed as a novel anticancer mechanism for biased β-blockers such as carvedilol. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced peroxynitrite mediated damage in diaphragm.

    Science.gov (United States)

    Ozdülger, Ali; Cinel, Ismail; Unlü, Ali; Cinel, Leyla; Mavioglu, Ilhan; Tamer, Lülüfer; Atik, Ugur; Oral, Ugur

    2002-07-01

    Although the precise mechanism by which sepsis causes impairment of respiratory muscle contractility has not been fully elucidated, oxygen-derived free radicals are thought to play an important role. In our experimental study, the effects of poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were randomly divided into four groups. The first group (control; n=8) received saline solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3-AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before administration of saline solution while the fourth group (LPS+3-AB, n=8) received 3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine anesthesia diapraghmatic specimens were obtained and the rats were decapitated. Diaphragmatic specimens were divided into four parts, three for biochemical analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)-ATPase levels were found to be decreased and tissue MDA and 3-NT levels were found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained similar to those in the control group (P<0.05). Histopathologic examination of diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)-ATPase activity in endotoxemia. These results highlights the importance of nitric oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical mediated injury. PARS inhibitors should further be investigated as a new thearapetic alternative in sepsis treatment.

  1. Chewing-induced hypertension in afferent baroreflex failure: A sympathetic response?

    Science.gov (United States)

    Mora, Cristina Fuente; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

    2016-01-01

    Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure due to baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD, and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and RR intervals were measured continuously while chewing gum (n= 15), swallowing food (n=20) and distending the stomach with a gastrostomy feed (n=9). Responses were compared to those of normal controls (n=10) and of patients with autonomic failure (n=10) who have chronically impaired sympathetic outflow. In patients with FD, swallowing food was associated with a marked, but transient pressor response (p<0.0001) and additional signs of sympathetic activation including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in controls (p=0.0001), but was absent in patients with autonomic failure. In patients with FD distending the stomach with a gastrostomy feed failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure that is exaggerated in patients with FD due to blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD. PMID:26435473

  2. Reflex sympathetic dystrophy: reflections from a clinician.

    Science.gov (United States)

    Small, Eric

    2007-05-01

    Reflex sympathetic dystrophy is defined as chronic musculoskeletal pain and autonomic dysfunction. It is a difficult diagnosis to make, and the adolescent often sees many specialists before arriving at the correct diagnosis. In this article I review reflex sympathetic dystrophy and reflect on the differential diagnosis, pertinent medical history, personal characteristics of patients with reflex sympathetic dystrophy, physical examination, and laboratory evaluation. Principles of management are considered, including physical therapy, pharmacology, psychological therapy, and alternative therapies. Accurate diagnosis and management are critical for not prolonging the adolescent's and the family's suffering. It is important to provide aggressive physical therapy, stress management, relaxation training, and close follow-up. It is also critical to avoid immobilization, surgery, or invasive procedures and unnecessary tests.

  3. Polyphenols, Antioxidants and the Sympathetic Nervous System.

    Science.gov (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2017-11-14

    A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity and metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympatho-excitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel

  4. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease.

    Science.gov (United States)

    Malpas, Simon C

    2010-04-01

    This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.

  5. The television, school, and family smoking prevention and cessation project. VIII. Student outcomes and mediating variables.

    Science.gov (United States)

    Flay, B R; Miller, T Q; Hedeker, D; Siddiqui, O; Britton, C F; Brannon, B R; Johnson, C A; Hansen, W B; Sussman, S; Dent, C

    1995-01-01

    This paper presents the student outcomes of a large-scale, social-influences-based, school and media-based tobacco use prevention and cessation project in Southern California. The study provided an experimental comparison of classroom delivery with television delivery and the combination of the two in a 2 x 2 plus 1 design. Schools were randomly assigned to conditions. Control groups included "treatment as usual" and an "attention control" with the same outcome expectancies as the treatment conditions. Students were surveyed twice in grade 7 and once in each of grades 8 and 9. The interventions occurred during grade 7. We observed significant effects on mediating variables such as knowledge and prevalence estimates, and coping effort. The knowledge and prevalence estimates effects decayed partially but remained significant up to a 2-year follow-up. The coping effort effect did not persist at follow-ups. There were significant main effects of both classroom training and TV programming on knowledge and prevalence estimates and significant interactions of classroom and TV programming on knowledge (negative), disapproval of parental smoking, and coping effort. There were no consistent program effects on refusal/self-efficacy, smoking intentions, or behavior. Previous reports demonstrated successful development and pilot testing of program components and measures and high acceptance of the program by students and parents. The lack of behavioral effects may have been the result of imperfect program implementation or low base rates of intentions and behavior.

  6. Specific egg yolk immunoglobulin as a new preventive approach for Shiga-toxin-mediated diseases.

    Directory of Open Access Journals (Sweden)

    Paola Neri

    Full Text Available Shiga toxins (Stxs are involved in the development of severe systemic complications associated with enterohemorrhagic Escherichia coli (EHEC infection. Various neutralizing agents against Stxs are under investigation for management of EHEC infection. In this study, we immunized chickens with formalin-inactivated Stx-1 or Stx-2, and obtained immunoglobulin Y (IgY from the egg yolk. Anti-Stx-1 IgY and anti-Stx-2 IgY recognized the corresponding Stx A subunit and polymeric but not monomeric B subunit. Anti-Stx-1 IgY and anti-Stx-2 IgY suppressed the cytotoxicity of Stx-1 and Stx-2 to HeLa 229 cells, without cross-suppressive activity. The suppressive activity of these IgY was abrogated by pre-incubation with the corresponding recombinant B subunit, which suggests that the antibodies directed to the polymeric B subunits were predominantly involved in the suppression. In vivo, the intraperitoneal or intravenous administration of these IgY rescued mice from death caused by intraperitoneal injection of the corresponding toxin at a lethal dose. Moreover, oral administration of anti-Stx-2 IgY reduced the mortality of mice infected intestinally with EHEC O157:H7. Our results therefore suggest that anti-Stx IgY antibodies may be considered as preventive agents for Stx-mediated diseases in EHEC infection.

  7. Munchausen's syndrome simulating reflex sympathetic dystrophy.

    Science.gov (United States)

    Rodriguez-Moreno, J; Ruiz-Martin, J M; Mateo-Soria, L; Rozadilla, A; Roig-Escofet, D

    1990-01-01

    A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admissions to hospital and multiple explorations we discovered that she had induced her symptoms herself and a diagnosis of Munchausen's syndrome was made. As far as we know this presentation has not been previously reported and might help to explain the physiopathology of some signs of reflex sympathetic dystrophy. Images PMID:2270960

  8. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  9. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

    Directory of Open Access Journals (Sweden)

    Scott S Wildman

    2013-10-01

    Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

  11. Remote ischemic preconditioning prevents reduction in brachial artery flow-mediated dilation after strenuous exercise.

    Science.gov (United States)

    Bailey, Tom G; Birk, Gurpreet K; Cable, N Timothy; Atkinson, Greg; Green, Daniel J; Jones, Helen; Thijssen, Dick H J

    2012-09-01

    Strenuous exercise is associated with an immediate decrease in endothelial function. Repeated bouts of ischemia followed by reperfusion, known as remote ischemic preconditioning (RIPC), is able to protect the endothelium against ischemia-induced injury beyond the ischemic area. We examined the hypothesis that RIPC prevents the decrease in endothelial function observed after strenuous exercise in healthy men. In a randomized, crossover study, 13 healthy men performed running exercise preceded by RIPC of the lower limbs (4 × 5-min 220-mmHg bilateral occlusion) or a sham intervention (sham; 4 × 5-min 20-mmHg bilateral occlusion). Participants performed a graded maximal treadmill running test, followed by a 5-km time trial (TT). Brachial artery endothelial function was examined before and after RIPC or sham, as well as after the 5-km TT. We measured flow-mediated dilation (FMD), an index of endothelium-dependent function, using high-resolution echo-Doppler. We also calculated the shear rate area-under-the-curve (from cuff deflation to peak dilatation; SR(AUC)). Data are described as mean and 95% confidence intervals. FMD changed by 0.30). In the sham trial, FMD changed from 5.1 (4.4-5.9) to 3.7% (2.6-4.8) following the 5-km TT (P = 0.02). In the RIPC trial, FMD changed negligibly from 5.4 (4.4-6.4) post-IPC and 5.7% (4.6-6.8) post 5-km TT (P = 0.60). Baseline diameter, SR(AUC), and time-to-peak diameter were all increased following the 5-km TT (P < 0.05), but these changes did not influence the IPC-mediated maintenance of FMD. In conclusion, these data indicate that strenuous lower-limb exercise results in an acute decrease in brachial artery FMD of ~1.4% in healthy men. However, we have shown for the first time that prior RIPC of the lower limbs maintains postexercise brachial artery endothelium-dependent function at preexercise levels.

  12. A Salicylate Sympathetic Ink from Consumer Chemicals

    Science.gov (United States)

    Journal of Chemical Education, 2005

    2005-01-01

    A new sympathetic ink that produces a violet color upon development was developed to develop chemical demonstrations using consumer chemicals. The demonstration was to have a simple, relatively safe reagent system that could be used to make a brightly colored, highly visible "magic sign" for use in science outreach programs.

  13. Hyperpolarizing `α2'-adrenoceptors in rat sympathetic ganglia

    Science.gov (United States)

    Brown, D.A.; Caulfield, M.P.

    1979-01-01

    1 Receptors mediating catecholamine-induced hyperpolarization of isolated superior cervical sympathetic ganglia of the rat have been characterized by means of an extracellular recording method. 2 (-)-Noradrenaline (EC50, 1.7 ± 0.6 μM) produced an immediate low-amplitude (oxymetazoline (0.01 to 1 μM) and ergometrine (0.1 to 10 μM) produced a persistent, low-amplitude hyperpolarization, as though they were partial agonists. Responses to the agonists were blocked by yohimbine (1 μM) but not be prazosin (1 μM). 7 It is concluded that the adrenergic cell bodies in the ganglion were hyperpolarized through activation of the same type of α-receptor (`α2-receptors') as those present at adrenergic nerve terminals. PMID:218668

  14. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno......Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...

  15. Baroreflex control of renal sympathetic nerve activity in early heart failure assessed by the sequence method.

    Science.gov (United States)

    Lataro, Renata Maria; Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

    2017-06-01

    The integrity of the baroreflex control of sympathetic activity in heart failure (HF) remains under debate. We proposed the use of the sequence method to assess the baroreflex control of renal sympathetic nerve activity (RSNA). The sequence method assesses the spontaneous arterial pressure (AP) fluctuations and their related changes in heart rate (or other efferent responses), providing the sensitivity and the effectiveness of the baroreflex. Effectiveness refers to the fraction of spontaneous AP changes that elicits baroreflex-mediated variations in the efferent response. Using three different approaches, we showed that the baroreflex sensitivity between AP and RSNA is not altered in early HF rats. However, the sequence method provided evidence that the effectiveness of baroreflex in changing RSNA in response to AP changes is markedly decreased in HF. The results help us better understand the baroreflex control of the sympathetic nerve activity. In heart failure (HF), the reflex control of the heart rate is known to be markedly impaired; however, the baroreceptor control of the sympathetic drive remains under debate. Applying the sequence method to a series of arterial pressure (AP) and renal sympathetic nerve activity (RSNA), we demonstrated a clear dysfunction in the baroreflex control of sympathetic activity in rats with early HF. We analysed the baroreflex control of the sympathetic drive using three different approaches: AP vs. RSNA curve, cross-spectral analysis and sequence method between AP and RSNA. The sequence method also provides the baroreflex effectiveness index (BEI), which represents the percentage of AP ramps that actually produce a reflex response. The methods were applied to control rats and rats with HF induced by myocardial infarction. None of the methods employed to assess the sympathetic baroreflex gain were able to detect any differences between the control and the HF group. However, rats with HF exhibited a lower BEI compared to the

  16. Preventing Alcohol-Related Harm in College Students: Alcohol-Related Harm Prevention Program Effects on Hypothesized Mediating Variables

    Science.gov (United States)

    Graham, J. W.; Tatterson, J. W.; Roberts, M. M.; Johnston, S. E.

    2004-01-01

    The Alcohol-related Harm Prevention (AHP) program is a normative education and skill-acquisition program designed to reduce serious, long-term alcohol-related harm in college students. Without admonishing students not to drink, which is likely to fail in many student populations, the AHP program attempts to give students the necessary perceptions,…

  17. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno......Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

  18. Effects of cervical sympathetic nerve stimulation on the cerebral microcirculation: possible clinical implications.

    Science.gov (United States)

    Passatore, M; Deriu, F; Roatta, S; Grassi, C; Micieli, G

    1996-01-01

    The action of bilateral cervical sympathetic nerve (CSN) stimulation on mean cerebral blood flow (CBF) and on its rhythmical fluctuations was studied in normotensive rabbits by using laser-Doppler flowmetry (LDF). A reduction in mean CBF, mediated by alpha-adrenoceptors, was the predominant effect; it was more often present and larger in size in the vascular beds supplied by the carotid than in those supplied by the vertebro-basilar system. This suggests that the sympathetic action facilitates a redistribution of blood flow to the brain stem. The effect induced by CSN stimulation on CBF spontaneous oscillations was a consistent decrease in amplitude and an increase in frequency, irrespective of the changes produced on the mean level of CBF. The possible implications of the sympathetic action on the state of the blood-brain barrier (BBB) are discussed. Experimental and clinical data dealing with the influence of sympathetic activation on the cerebrovascular system have been compared. As a result the possibility of analysing the spontaneous oscillations of CBF for clinical purposes is suggested.

  19. Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.

    NARCIS (Netherlands)

    Buscher, H.C.J.L.; Lenders, J.W.M.; Wilder-Smith, O.H.G.; Sweep, C.G.J.; Goor, H. van

    2012-01-01

    BACKGROUND: Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments

  20. Cardiac sympathetic neurons provide trophic signal to the heart via β2-adrenoceptor-dependent regulation of proteolysis.

    Science.gov (United States)

    Zaglia, Tania; Milan, Giulia; Franzoso, Mauro; Bertaggia, Enrico; Pianca, Nicola; Piasentini, Eleonora; Voltarelli, Vanessa A; Chiavegato, David; Brum, Patricia C; Glass, David J; Schiaffino, Stefano; Sandri, Marco; Mongillo, Marco

    2013-02-01

    Increased cardiac sympathetic neuron (SN) activity has been associated with pathologies such as heart failure and hypertrophy, suggesting that cardiac innervation regulates cardiomyocyte trophism. Whether continuous input from the SNs is required for the maintenance of the cardiomyocyte size has not been determined thus far. To address the role of cardiac innervation in cardiomyocyte size regulation, we monitored the effect of pharmacological sympathetic denervation in mice on cardiac structure, function, and signalling from 24 h to 30 days in the absence of other pathological stimuli. SN ablation caused an immediate reduction in the cardiomyocyte size with minimal consequences on the resting contractile function. Atrophic remodelling was mediated by the ubiquitin-proteasome system through FOXO-dependent early induction of the muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1, which was followed by activation of the autophagy-lysosome system. MuRF1 was found to be determinant in denervation atrophy as remodelling did not develop in denervated MuRF1 knock-out (KO) hearts. These effects were caused by decreased basal stimulation of cardiomyocyte β2-adrenoceptor (AR), as atrophy was prevented by treatment of denervated mice with the β2-AR agonist clenbuterol. Consistent with these data, we also observed that β2-AR KO mice showed cardiac atrophy at rest. Cardiac SNs are strong regulators of the cardiomyocyte size via β2-AR-dependent repression of proteolysis, demonstrating that the neuro-cardiac axis operates constitutively for the determination of the physiological cardiomyocyte size. These results are of great clinical relevance given the role of β-AR in cardiovascular diseases and their modulation in therapy.

  1. Inhibition of chaperone-mediated autophagy prevents glucotoxicity in the Caenorhabditis elegans mev-1 mutant by activation of the proteasome.

    Science.gov (United States)

    Eisermann, Dorothé Jenni; Wenzel, Uwe; Fitzenberger, Elena

    2017-02-26

    Chronic hyperglycemia is a hallmark of diabetes mellitus and the main cause of diabetes-associated complications. Increased intracellular glucose levels lead to damaged proteins and in consequence disturb cellular proteostasis. As an important contributor to the maintenance and restoration of proteostasis, autophagy mediates the lysosomal degradation of damaged proteins or entire cellular organelles. In the present study we used the stress-sensitive mev-1 mutant of the nematode Caenorhabditis elegans in order to assess the role of lmp-2, a homologue of the lysosome associated membrane protein type 2A, in the context of glucotoxicity, which was achieved by feeding glucose in a liquid medium. Knockdown of lmp-2 by RNA interference completely prevented the survival reduction caused by glucose under heat stress. Those effects were associated with the prevention of (1) increased lysosome formation and (2) reduction of proteasomal activity, which were observed under glucose feeding. Finally, the survival reduction due to knockdown of ubiquitin remained unaffected by the additional lmp-2 knockdown in the absence or presence of glucose. In conclusion, our study provides evidence that lmp-2, a key player in chaperone-mediated autophagy, is functional in C. elegans, too. Inhibition of lmp-2 prevents the reduction of proteasomal activity by glucose and thereby prevents also glucotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Underwater sympathetic detonation of pellet explosive

    Science.gov (United States)

    Kubota, Shiro; Saburi, Tei; Nagayama, Kunihito

    2017-06-01

    The underwater sympathetic detonation of pellet explosives was taken by high-speed photography. The diameter and the thickness of the pellet were 20 and 10 mm, respectively. The experimental system consists of the precise electric detonator, two grams of composition C4 booster and three pellets, and these were set in water tank. High-speed video camera, HPV-X made by Shimadzu was used with 10 Mfs. The underwater explosions of the precise electric detonator, the C4 booster and a pellet were also taken by high-speed photography to estimate the propagation processes of the underwater shock waves. Numerical simulation of the underwater sympathetic detonation of the pellet explosives was also carried out and compared with experiment.

  3. Reflex sympathetic dystrophy syndrome in a child.

    Science.gov (United States)

    Badri, Talel; Ben Jennet, Salima; Fenniche, Samy; Benmously, Rym; Mokhtar, Inçaf; Hammami, Hatem

    2011-06-01

    Reflex sympathetic dystrophy syndrome (RSDS) is a painful condition that usually follows regional trauma. We report the case of a 13-year-old girl that was seen for a painful swelling of the right hand associated with palmar hyperhidrosis, which occurred after a trauma to the hand. Bone scan images showed early tissue abnormality, which was more significant on the right hand and wrist, as well as moderate bone uptake on the right side. Nonsteroidal anti-inflammatory drugs and alternating hot and cold baths led to a marked improvement. RSDS occurs following trauma or subsequent to various diseases or drug intake. This syndrome is related to impaired tissue microvasculature under the influence of abnormal sympathetic reflex hyperactivity. Bone scan is the diagnostic procedure of choice in RSDS, but it may be normal. Physiotherapy should be preferred in pediatric cases.

  4. Sympathetic blocks for visceral cancer pain management

    DEFF Research Database (Denmark)

    Mercadante, Sebastiano; Klepstad, Pal; Kurita, Geana Paula

    2015-01-01

    The neurolytic blocks of sympathetic pathways, including celiac plexus block (CPB) and superior hypogastric plexus block (SHPB) , have been used for years. The aim of this review was to assess the evidence to support the performance of sympathetic blocks in cancer patients with abdominal visceral...... pain. Only comparison studies were included. All data from the eligible trials were analyzed using the GRADE system. Twenty-seven controlled studies were considered. CPB, regardless of the technique used, improved analgesia and/or decrease opioid consumption, and decreased opioid-induced adverse...... effects in comparison with a conventional analgesic treatment. In one study patients treated with superior hypogastric plexus block (SHPB) had a decrease in pain intensity and a less morphine consumption, while no statistical differences in adverse effects were found. The quality of these studies...

  5. Diabetic cardiac autonomic dysfunction. Parasympathetic versus sympathetic

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Akihiko; Kurata, Chinori; Sugi, Toshihiko; Mikami, Tadashi; Shouda, Sakae [Hamamatsu Univ. School of Medicine, Shizuoka (Japan)

    1999-04-01

    Diabetic cardiac autonomic dysfunction often causes lethal arrhythmia and sudden cardiac death. {sup 123}I-Metaiodobenzylguanidine (MIBG) can evaluate cardiac sympathetic dysfunction, and analysis of heart rate variability (HRV) can reflect cardiac parasympathetic activity. We examined whether cardiac parasympathetic dysfunction assessed by HRV may correlate with sympathetic dysfunction assessed by MIBG in diabetic patients. In 24-hour electrocardiography, we analyzed 4 HRV parameters: high-frequency power (HF), HF in the early morning (EMHF), rMSSD and pNN50. MIBG planar images and SPECT were obtained 15 minutes (early) and 150 minutes (late) after injection and the heart washout rate was calculated. The defect score in 9 left ventricular regions was scored on a 4 point scale (0=normal - 3=severe defect). In 20 selected diabetic patients without congestive heart failure, coronary artery disease and renal failure, parasympathetic HRV parameters had a negative correlation with the sum of defect scores (DS) in the late images (R=-0.47 to -0.59, p<0.05) and some parameters had a negative correlation with the washout rate (R=-0.50 to -0.55, p<0.05). In a total of 64 diabetic patients also, these parameters had a negative correlation with late DS (R=-0.28 to -0.35, p<0.05) and early DS (R=-0.27 to -0.32, p<0.05). The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one. (author)

  6. Using therapeutic jurisprudence and preventive law to examine disputants' best interests in mediating cases about physicians' practices: a guide for medical regulators.

    Science.gov (United States)

    Ferris, Lorraine E

    2004-01-01

    Therapeutic jurisprudence (TJ) and preventive law (PL) are used as two theoretical perspectives from which to examine the best interests of parties in mediation because of a dispute about a physician's practice. The focus is mediation provided by and/or for the medical regulator. The paper reviews the literature on TJ and PL, and their relationship to mediation, and demonstrates how medical regulators could benefit by working within a framework reflecting both these perspectives providing it does not involve an egregious matter. A TJ and PL framework would be of particular value in identifying cases for mediation and in evaluating resolutions to mediated disputes.

  7. Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

    Science.gov (United States)

    Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

    2000-01-01

    Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

  8. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

    Science.gov (United States)

    Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

    2017-01-01

    Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark

  9. The MEK-ERK pathway negatively regulates bim expression through the 3' UTR in sympathetic neurons

    Science.gov (United States)

    2011-01-01

    Background Apoptosis plays a critical role during neuronal development and disease. Developing sympathetic neurons depend on nerve growth factor (NGF) for survival during the late embryonic and early postnatal period and die by apoptosis in its absence. The proapoptotic BH3-only protein Bim increases in level after NGF withdrawal and is required for NGF withdrawal-induced death. The regulation of Bim expression in neurons is complex and this study describes a new mechanism by which an NGF-activated signalling pathway regulates bim gene expression in sympathetic neurons. Results We report that U0126, an inhibitor of the prosurvival MEK-ERK pathway, increases bim mRNA levels in sympathetic neurons in the presence of NGF. We find that this effect is independent of PI3-K-Akt and JNK-c-Jun signalling and is not mediated by the promoter, first exon or first intron of the bim gene. By performing 3' RACE and microinjection experiments with a new bim-LUC+3'UTR reporter construct, we show that U0126 increases bim expression via the bim 3' UTR. We demonstrate that this effect does not involve a change in bim mRNA stability and by using PD184352, a specific MEK1/2-ERK1/2 inhibitor, we show that this mechanism involves the MEK1/2-ERK1/2 pathway. Finally, we demonstrate that inhibition of MEK/ERK signalling independently reduces cell survival in NGF-treated sympathetic neurons. Conclusions These results suggest that in sympathetic neurons, MEK-ERK signalling negatively regulates bim expression via the 3' UTR and that this regulation is likely to be at the level of transcription. This data provides further insight into the different mechanisms by which survival signalling pathways regulate bim expression in neurons. PMID:21762482

  10. Pmch-deficiency in rats is associated with normal adipocyte differentiation and lower sympathetic adipose drive.

    Directory of Open Access Journals (Sweden)

    Joram D Mul

    Full Text Available The orexigenic neuropeptide melanin-concentrating hormone (MCH, a product of Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch is expressed in hypothalamic neurons that ultimately are components in the sympathetic nervous system (SNS drive to white and interscapular brown adipose tissue (WAT, iBAT, respectively. MCH binds to MCH receptor 1 (MCH1R, which is present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal WAT mass and adipocyte morphology (size and number throughout development, and indices of sympathetic activation in WAT and iBAT during adulthood. Moreover, using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1 adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and perirenal WAT mass by reducing adipocyte size, but not number. In line with this, in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic adipose drive in WAT and iBAT than wild-type rats. Collectively, our data indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation, whereas Pmch-deficiency in laboratory rats lowers adiposity throughout development and sympathetic adipose drive during adulthood.

  11. Mediators of the relationship between media literacy and body dissatisfaction in early adolescent girls: implications for prevention.

    Science.gov (United States)

    McLean, Siân A; Paxton, Susan J; Wertheim, Eleanor H

    2013-06-01

    This study examined in young adolescent girls the fit of a theoretical model of the contribution of media literacy to body dissatisfaction via the mediating influences of internalisation of media ideals and appearance comparisons. Female Grade 7 students (N=469) completed self-report assessments of media literacy, internalisation, appearance comparisons, body dissatisfaction, and media exposure. Strong, significant inverse associations between media literacy and body dissatisfaction, internalisation, and appearance comparisons were observed. Path analysis revealed that a slightly modified revision of the model provided a good fit to the data. Specifically, body dissatisfaction was influenced directly by appearance comparisons, internalisation, and body mass index, and indirectly by media literacy and media exposure. Indirect pathways were mediated by appearance comparisons and internalisation. Thus, a relationship between media literacy and eating disorder risk factors was observed. Findings may explain positive outcomes of media literacy interventions in eating disorder prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

    DEFF Research Database (Denmark)

    Vagn Nielsen, H; Hasselström, K; Feldt-Rasmussen, U

    1987-01-01

    Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstrict......Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic.......02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment....

  13. Epidermal growth factor prevents thallium(I)- and thallium(III)-mediated rat pheochromocytoma (PC12) cell apoptosis.

    Science.gov (United States)

    Pino, María Teresa Luján; Marotte, Clarisa; Verstraeten, Sandra Viviana

    2017-03-01

    We have reported recently that the proliferation of PC12 cells exposed to micromolar concentrations of Tl(I) or Tl(III) has different outcomes, depending on the absence (EGF - cells) or the presence (EGF + cells) of epidermal growth factor (EGF) added to the media. In the current work, we investigated whether EGF supplementation could also modulate the extent of Tl(I)- or Tl(III)-induced cell apoptosis. Tl(I) and Tl(III) (25-100 μM) decreased cell viability in EGF - but not in EGF + cells. In EGF - cells, Tl(I) decreased mitochondrial potential, enhanced H 2 O 2 generation, and activated mitochondrial-dependent apoptosis. In addition, Tl(III) increased nitric oxide production and caused a misbalance between the anti- and pro-apoptotic members of Bcl-2 family. Tl(I) increased ERK1/2, JNK, p38, and p53 phosphorylation in EGF - cells. In these cells, Tl(III) did not affect ERK1/2 and JNK phosphorylation but increased p53 phosphorylation that was related to the promotion of cell senescence. In addition, this cation significantly activated p38 in both EGF - and EGF + cells. The specific inhibition of ERK1/2, JNK, p38, or p53 abolished Tl(I)-mediated EGF - cell apoptosis. Only when p38 activity was inhibited, Tl(III)-mediated apoptosis was prevented in EGF - and EGF + cells. Together, current results indicate that EGF partially prevents the noxious effects of Tl by preventing the sustained activation of MAPKs signaling cascade that lead cells to apoptosis and point to p38 as a key mediator of Tl(III)-induced PC12 cell apoptosis.

  14. Electric sympathetic block: a review of electrotherapy physics.

    Science.gov (United States)

    Schwartz, R G

    1991-01-01

    Electric sympathetic block is the procedure whereby blockage of the sympathetic nerve fiber is achieved by applying controlled electrical pulses via electrodes placed on the skin. An electric block of the sympathetic fiber can occur with a direct monophasic current to achieve an anodal block, a middle-frequency or Endosan current to effect sustained depolarization, or an interferential current to achieve a fatiguing effect. The physics and theoretical framework underlying the currents used in this procedure will be reviewed.

  15. Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model

    NARCIS (Netherlands)

    S.K. Halstead (Susan); F.M.P. Zitman (Femke); P.D. Humphreys (Peter); K. Greenshields (Kay); J.J. Verschuuren (Jan); B.C. Jacobs (Bart); R.P. Rother (Russell); J.J. Plomp (Jaap); H.J. Willison (Hugh)

    2008-01-01

    textabstractAnti-GQ1b ganglioside antibodies are the serological hallmark of the Miller Fisher syndrome (MFS) variant of the paralytic neuropathy, Guillain- Barré syndrome, and are believed to be the principal pathogenic mediators of the disease. In support of this, we previously showed in an in

  16. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons

    NARCIS (Netherlands)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stephanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade

  17. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  18. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    Science.gov (United States)

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. ©2015 American Association for Cancer Research.

  19. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    Science.gov (United States)

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-06

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis.

  20. Reflex sympathetic dystrophy following pacemaker insertion.

    Science.gov (United States)

    Londhey, Vikram A; Singh, Nishant; Kini, Seema

    2011-09-01

    A 55 year old male presented with pain and swelling over dorsum of right hand and small joints, and loss of sweating over right hand since two months. He was a known case of mitral valve prolapse (MVP) with mitral regurgitation and complete heart block for which pacemaker was implanted 1 year back. Bilateral wrist X-ray was suggestive of pronounced demineralization (osteopenia) in the right hand. He was thus diagnosed to have reflex sympathetic dystrophy syndrome (RSDS) considered to be induced by pacemaker insertion. After treatment with amitryptiline and indomethacin his symptoms dramatically improved.

  1. Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering

    Science.gov (United States)

    Spindler, Volker; Rötzer, Vera; Dehner, Carina; Kempf, Bettina; Gliem, Martin; Radeva, Mariya; Hartlieb, Eva; Harms, Gregory S.; Schmidt, Enno; Waschke, Jens

    2013-01-01

    In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due to limited insights into disease pathogenesis, current therapy relies primarily on nonspecific long-term immunosuppression. Both direct inhibition of DSG transinteraction and altered intracellular signaling by p38 MAPK likely contribute to the loss of cell adhesion. Here, we applied a tandem peptide (TP) consisting of 2 connected peptide sequences targeting the DSG adhesive interface that was capable of blocking autoantibody-mediated direct interference of DSG3 transinteraction, as revealed by atomic force microscopy and optical trapping. Importantly, TP abrogated autoantibody-mediated skin blistering in mice and was effective when applied topically. Mechanistically, TP inhibited both autoantibody-induced p38 MAPK activation and its association with DSG3, abrogated p38 MAPK-induced keratin filament retraction, and promoted desmosomal DSG3 oligomerization. These data indicate that p38 MAPK links autoantibody-mediated inhibition of DSG3 binding to skin blistering. By limiting loss of DSG3 transinteraction, p38 MAPK activation, and keratin filament retraction, which are hallmarks of pemphigus pathogenesis, TP may serve as a promising treatment option. PMID:23298835

  2. Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway.

    Science.gov (United States)

    Lee, J-H; Jeong, J-K; Park, S-Y

    2014-10-10

    Prion diseases are neurodegenerative and infectious disorders that involve accumulation of misfolded scrapie prion protein, and which are characterized by spongiform degeneration. Autophagy, a major homeostatic process responsible for the degradation of cytoplasmic components, has garnered attention as the potential target for neurodegenerative diseases such as prion disease. We focused on protective effects of sulforaphane found in cruciferous vegetables on prion-mediated neurotoxicity and the mechanism of sulforaphane related to autophagy. In human neuroblastoma cells, sulforaphane protected prion protein (PrP) (106-126)-mediated neurotoxicity and increased autophagy flux marker microtubule-associated protein 1 light chain 3-II protein levels, following a decrease of p62 protein level. Pharmacological and genetical inhibition of autophagy by 3MA, wortmannin and knockdown of autophagy-related 5 (ATG5) led to block the effect of sulforaphane against PrP (106-126)-induced neurotoxicity. Furthermore we demonstrated that both sulforaphane-induced autophagy and protective effect of sulforaphane against PrP (106-126)-induced neurotoxicity are dependent on the AMP-activated protein kinase (AMPK) signaling. The present results indicated that sulforaphane of cruciferous vegetables enhanced autophagy flux led to the protection effects against prion-mediated neurotoxicity, which was regulated by AMPK signaling pathways in human neuron cells. Our data also suggest that sulforaphane has a potential value as a therapeutic tool in neurodegenerative disease including prion diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Guan-gui Chen

    2015-01-01

    Full Text Available Polyethyleneimine-polyethylene glycol (PEI-PEG, a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

  4. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance.

    Science.gov (United States)

    Huang, Chien-Ning; Wang, Chau-Jong; Yang, Yi-Sun; Lin, Chih-Li; Peng, Chiung-Huei

    2016-01-01

    Diabetic nephropathy has a significant socioeconomic impact, but its mechanism is unclear and needs to be examined. Hibiscus sabdariffa polyphenols (HPE) inhibited high glucose-induced angiotensin II receptor-1 (AT-1), thus attenuating renal epithelial mesenchymal transition (EMT). Recently, we reported HPE inhibited dipeptidyl-peptidase-4 (DPP-4, the enzyme degrades type 1 glucagon-like peptide (GLP-1)), which mediated insulin resistance signals leading to EMT. Since free fatty acids can realistically bring about insulin resistance, using the palmitate-stimulated cell model in contrast with type 2 diabetic rats, in this study we examined if insulin resistance causes renal EMT, and the preventive effect of HPE. Our findings reveal that palmitate hindered 30% of glucose uptake. Treatment with 1 mg mL(-1) of HPE and the DPP-4 inhibitor linagliptin completely recovered insulin sensitivity and palmitate-induced signal cascades. HPE inhibited DPP-4 activity without altering the levels of DPP-4 and the GLP-1 receptor (GLP-1R). HPE decreased palmitate-induced phosphorylation of Ser307 of insulin receptor substrate-1 (pIRS-1 (S307)), AT-1 and vimentin, while increasing phosphorylation of phosphatidylinositol 3-kinase (pPI3K). IRS-1 knockdown revealed its essential role in mediating downstream AT-1 and EMT. In type 2 diabetic rats, it suggests that HPE concomitantly decreased the protein levels of DPP-4, AT-1, vimentin, and fibronectin, but reversed the in vivo compensation of GLP-1R. In conclusion, HPE improves insulin sensitivity by attenuating DPP-4 and the downstream signals, thus decreasing AT-1-mediated tubular-interstitial EMT. HPE could be an adjuvant to prevent diabetic nephropathy.

  5. RO-3306 prevents postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro.

    Science.gov (United States)

    Prasad, Shilpa; Koch, Biplob; Chaube, Shail K

    2016-03-01

    Postovulatory aging-mediated spontaneous exit from metaphase-II (M-II) arrest deteriorates egg quality and limits assisted reproductive technologies outcome (ART) outcome. Present study was aimed to find out whether RO-3306, specific cyclin dependent kinase 1 (Cdk1) inhibitor could protect against postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro. Freshly ovulated M-II arrested eggs were exposed to various concentrations of RO-3306 for 3h in vitro. The morphological changes, percentage of spontaneous exit from M-II arrest, total and specific phosphorylation status of Cdk1, cyclin B1 level and Cdk1 activity were analyzed. Data suggest that RO-3306 protected postovulatory aging-mediated spontaneous exit from M-II arrest in a concentration-dependent manner. Postovulatory aging increased Thr14/Tyr15 phosphorylated Cdk1 level, decreased Thr161 phosphorylated Cdk1 as well as cyclin B1 levels and increased Cdk1 activity in aged eggs cultured in vitro. On the other hand, RO-3306 protected postovulatory aging-induced changes in specific phosphorylation of Cdk1, cyclin B1 level, inhibited the kinase activity and prevented spontaneous exit from M-II arrest. Our results suggest that postovulatory aging destabilizes MPF by modulating specific phosphorylation of Cdk1 and cyclin B1 level. RO-3306 prevented these changes and maintained M-II arrest in rat eggs cultured in vitro. Hence, maintenance of M-II arrest in ovulated eggs using RO-3306 could be beneficial to increase the number of eggs available for various ART programs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. [A case of prolonged paroxysmal sympathetic hyperactivity].

    Science.gov (United States)

    Yamamoto, Akiko; Ide, Shuhei; Iwasaki, Yuji; Kaga, Makiko; Arima, Masataka

    2016-03-01

    We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter- paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two rea- sons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory: inhibitory ratio (EIR) model proposed by Baguley was considered while dis- cussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH.

  7. Intergenerational Continuity in Child Maltreatment: Mediating Mechanisms and Implications for Prevention

    Science.gov (United States)

    Berlin, Lisa J.; Appleyard, Karen; Dodge, Kenneth A.

    2011-01-01

    In the interest of improving child maltreatment prevention, this prospective, longitudinal, community-based study of 499 mothers and their infants examined (a) direct associations between mothers' experiences of childhood maltreatment and their offspring's maltreatment, and (b) mothers' mental health problems, social isolation, and social…

  8. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  9. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

  10. Epithelioid sarcoma presenting as the reflex sympathetic dystrophy syndrome.

    Science.gov (United States)

    Summers, C. L.; Shahi, M.

    1987-01-01

    A case of reflex sympathetic dystrophy caused by an epithelioid sarcoma is presented. This is the first report of a local peripheral tumour associated with the reflex sympathetic dystrophy syndrome. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3671265

  11. Reflex sympathetic dystrophy: Early treatment and psychological aspects

    NARCIS (Netherlands)

    Geertzen, J.H.B.; De Bruijn, H.; De Bruijn-Kofman, A.T.; Arendzen, J.H.

    1994-01-01

    We report the results of two prospective studies of early treatment and psychological aspects in a series of 26 patients with sympathetic reflex dystrophy of the hand in which treatment was started within 3 months after diagnosis. Ismelin blocks is an often used therapy in sympathetic reflex

  12. Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction

    NARCIS (Netherlands)

    Wernli, G.; Hasan, W.; Bhattacherjee, A.; Rooijen, van N.; Smith, P.K.

    2009-01-01

    Myocardial infarction induces sympathetic axon sprouting adjacent to the necrotic region, and this has been implicated in the etiology of arrhythmias resulting in sudden cardiac death. Previous studies show that nerve growth factor (NGF) is essential for enhanced post-infarct sympathetic sprouting,

  13. Layers of dendritic cell-mediated T cell tolerance, their regulation and the prevention of autoimmunity

    Directory of Open Access Journals (Sweden)

    Christian Thomas Mayer

    2012-07-01

    Full Text Available The last decades of Nobel prize-honored research have unequivocally proven a key role of dendritic cells (DCs at controlling both T cell immunity and tolerance. A tight balance between these opposing DC functions ensures immune homeostasis and host integrity. Its perturbation could explain pathological conditions such as the attack of self tissues, chronic infections and tumor immune evasion. While recent insights into the complex DC network help to understand the contribution of individual DC subsets to immunity, the tolerogenic functions of DCs only begin to emerge. As these consist of many different layers, the definition of a ‘tolerogenic DC’ is subjected to variation. Moreover, the implication of DCs and DC subsets in the suppression of autoimmunity are incompletely resolved. In this review, we point out conceptual controversies and dissect the various layers of DC-mediated T cell tolerance. These layers include central tolerance, Foxp3+ regulatory T cells, anergy/deletion and negative feedback regulation. The mode and kinetics of antigen presentation is highlighted as an additional factor shaping tolerance. Special emphasis is given to the interaction between layers of tolerance as well as their differential regulation during inflammation. Furthermore, potential technical caveats of DC depletion models are considered. Finally, we summarize our current understanding of DC-mediated tolerance and its role for the suppression of autoimmunity. Understanding the mechanisms of DC-mediated tolerance and their complex interplay is fundamental for the development of selective therapeutic strategies, e.g. for the modulation of autoimmune responses or for the immunotherapy of cancer.

  14. Processes of Change in Preventing Alcohol Exposed Pregnancy: A Mediation Analysis

    Science.gov (United States)

    Parrish, Danielle E.; von Sternberg, Kirk; Castro, Yessenia; Velasquez, Mary M.

    2016-01-01

    Objective To examine mechanisms of the treatment effect for CHOICES, a motivational intervention to reduce risk of alcohol exposed pregnancy (AEP). Grounded in constructs from the Transtheoretical Model (TTM) and Motivational Interviewing (MI), the intervention targeted: risk drinking (>4 drinks/day or >7 drinks/week); ineffective contraception; and AEP risk (both behaviors). The experiential and behavioral processes of change (POC), posited to describe the mechanisms through which individual behavior change occurs, were examined. It was hypothesized that each of the targeted treatment outcomes at 9-month follow-up would be mediated by the experiential POC at 3-months, and that these would then be mediated by the behavioral POC at 9-months. Method 830 women at-risk for AEP were randomized to CHOICES (Information Plus Counseling; IPC) condition (n=416) or Information Only (IO) condition (n=414). Primary outcomes and proposed mediators (POC) were assessed at 3- and 9-months. Path analyses using weighted least squares estimation with mean- and variance-adjusted chi-square statistic were conducted separately for each outcome. Results Model fit indices indicated good fit, and the indirect effect of treatment on outcome via POC was significant for hypothesized models predicting risky drinking and ineffective contraception. The indirect effect of treatment on AEP risk through POC for ineffective contraception was significant, but the indirect effect of POC for risky drinking was not. Conclusions These findings support the temporal relationship between experiential and behavioral POC consistent with the TTM. Opportunistic, motivation-based interventions may benefit from directly targeting experiential POC early in treatment and behavioral POC later in treatment. PMID:27176661

  15. Differential Toxicities of Intraneurally Injected Mercuric Chloride for Sympathetic and Somatic Motor Fibers: An Ultrastructural Study

    Directory of Open Access Journals (Sweden)

    Shih-Jung Cheng

    2011-02-01

    Conclusion: This study demonstrated an undue susceptibility of sympathetic fibers to mercury intoxication. The mechanisms that underlie the selective reaction of sympathetic fibers to mercury warrant further investigation.

  16. Sympathetic block by metal clips may be a reversible operation

    DEFF Research Database (Denmark)

    Thomsen, Lars L; Mikkelsen, Rasmus T; Derejko, Miroslawa

    2014-01-01

    the sympathetic chain vary tremendously. Most surgeons transect or resect the sympathetic chain, but application of a metal clip that blocks transmission of nerve impulses in the sympathetic chain is used increasingly worldwide. This approach offers potential reversibility if patients regret surgery......, but the question of reversibility remains controversial. Two recent experimental studies found severe histological signs of nerve damage 4-6 weeks after clip removal, but they only used conventional histopathological staining methods. METHODS: Thoracoscopic clipping of the sympathetic trunk was performed in adult...... sheep, and the clip was removed thoracoscopically after 7 days. Following another 4 weeks (n = 6) or 12 weeks (n = 3), the sympathetic trunks were harvested and analysed by conventional and specific nerve tissue immunohistochemical stains (S100, neurofilament protein and synaptophysin...

  17. LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZWF1 Mice

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    Annica Hedberg

    2013-01-01

    Full Text Available We have previously demonstrated that continuous infusion of low molecular weight (LMW heparin delays autoantibody production and development of lupus nephritis in (NZBxNZWF1 (B/W mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors. Splenocytes taken from B/W mice were stimulated with nucleosomes with or without the presence of heparin. Splenocyte cell proliferation as thymidine incorporation and the expression of costimulatory molecules and cell activation markers were measured. Heparin treatment of B/W mice reduced the in vivo expression of CCR2, IL1β, and TLR7 compared to untreated B/W mice. Nucleosome-induced cell proliferation of splenocytes was not influenced by heparin. The expression of CD80, CD86, CD69, CD25, CTLA-4, and TLR 2, 7, 8, and 9 was upregulated upon stimulation by nucleosomes, irrespective of whether heparin was added to the cell culture or not. In conclusion, treatment with heparin lowers the kidney expression of proinflammatory mediators in B/W mice but does not affect nucleosomal activation of splenocytes.

  18. Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections.

    Science.gov (United States)

    Müllbacher, A; Wallich, R; Moyer, R W; Simon, M M

    1999-06-15

    Previous observations that the highly conserved poxvirus-encoded serpins inhibit cytotoxic activities of alloreactive CTL via granule and/or Fas-mediated pathways was taken to indicate their involvement in immune evasion by poxviruses. We now show that interference with 51Cr release from target cells by ectromelia and cowpoxvirus is limited to alloreactive but not MHC-restricted CTL. The data are in support of the paramount importance of CTL and its effector molecule perforin in the recovery from primary ectromelia virus infection and question the role of serpins in the evasion of poxviruses from killing by CTL. Further analysis of poxvirus interference with target cell lysis by alloreactive CTL revealed that suppression primarily affects the Fas-mediated, and to a lesser extent, the granule exocytosis pathway. Serpin-2 is the main contributor to suppression for both killing pathways. In addition, inhibition of lysis was shown to be both target cell type- and MHC allotype-dependent. We hypothesize that differences in TCR affinities and/or state of activation between alloreactive and MHC-restricted CTL as well as the quality (origin) of target cells are responsible for the observed phenomenon.

  19. Meloxicam prevents COX-2-mediated post-surgical inflammation but not pain following laparotomy in mice.

    Science.gov (United States)

    Roughan, J V; Bertrand, H G M J; Isles, H M

    2016-02-01

    Inflammation is thought to be a major contributor to post-surgical pain, so non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesics. However, compared to rats, considerably less is known as to how successfully these prevent pain in mice. A fluorescent COX-2 selective probe was used for the first time to evaluate the post-surgical anti-inflammatory effects of meloxicam, and automated behaviour analyses (HomeCageScan; HCS), the Mouse Grimace Scale (MGS) and body weight changes to assess its pain-preventative properties. Groups of 8-9 BALB/c mice were subcutaneously injected with saline (0.3 mL) or meloxicam at (1, 5 or 20 mg/kg) 1 h before a 1.5-cm midline laparotomy. The probe or a control dye (2 mg/kg) was injected intravenously 3 h later. Imaging was used to quantify inflammation at 7, 24 and 48 h following surgery. HCS data and MGS scores were respectively obtained from video recordings and photographs before surgery and 24 h later. Post-surgical inflammation was dose dependently reduced by meloxicam; with 5 or 20 mg/kg being most effective compared to saline. However, all mice lost weight, MGS scores increased and behavioural activity was reduced by surgery for at least 24 h with no perceivable beneficial effect of meloxicam on any of these potentially pain-associated changes. Although meloxicam prevented inflammation, even large doses did not prevent post-laparotomy pain possibly arising due to a range of factors, including, but not limited to inflammation. MGS scoring can be applied by very naïve assessors and so should be effective for cage-side use. © 2015 European Pain Federation - EFIC®

  20. Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response.

    Science.gov (United States)

    Brindley, Rebecca L; Bauer, Mary Beth; Blakely, Randy D; Currie, Kevin P M

    2017-05-17

    Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice or chronic pharmacological block) has been reported to augment the sympathetic stress response. Alterations to serotonergic signaling in the CNS and thus central drive to the peripheral sympathetic nervous system are presumed to underlie this augmentation. Although less widely recognized, SERT is robustly expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT but accumulate small amounts by SERT-mediated uptake. Recent evidence demonstrated that 5-HT 1A receptors inhibit catecholamine secretion from adrenal chromaffin cells via an atypical mechanism that does not involve modulation of cellular excitability or voltage-gated Ca 2+ channels. This raises the possibility that the adrenal medulla is a previously unrecognized peripheral hub for serotonergic control of the sympathetic stress response. As a framework for future investigation, a model is proposed in which stress-evoked adrenal catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.

  1. Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training.

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    Rebecca L Scalzo

    Full Text Available The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21 were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11. The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE, but was increased during hypoxia mediated sympathetic activation (368±135; this response was abrogated (P = 0.035 with clonidine (269±93. Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21. Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5 was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT. SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046 but did not affect FNDC5 (P = 0.79. Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045 and increased in females (139±14 vs. 170±18. Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.

  2. Sleep deprivation in the rat: XI. The effect of guanethidine-induced sympathetic blockade on the sleep deprivation syndrome.

    Science.gov (United States)

    Pilcher, J J; Bergmann, B M; Fang, V S; Refetoff, S; Rechtschaffen, A

    1990-06-01

    In earlier studies, rats totally deprived of sleep by a disk-over-water apparatus (TSD rats) had shown an increase in energy expenditure (EE) that could not be explained by increased motor activity or the metabolic expense of wakefulness. Excessive activation of a calorigenic mediator was a possibility, and norepinephrine-mediated sympathetic activation was the most likely candidate, because plasma norepinephrine (NE) levels had risen sharply in TSD rats. To determine whether this activation was necessary for increased EE in sleep deprived rats, the peripheral sympathetic blocking agent guanethidine (GU) was administered to six sleep-deprived (GD) rats and their yoked control (GC) rats. GU attenuated the increase in NE previously seen in TSD rats, but the increase in EE was not attenuated. Apparently, NE-mediated sympathetic activation was not critical for increased EE in sleep-deprived rats. On the other hand, plasma epinephrine (EPI) levels were significantly increased in GD (but not in GC) rats above those previously seen in TSD rats, suggesting the substitution of one calorigenic mediator for another in response to an abnormally elevated need for EE. Temperature data suggest that increased need for EE could arise from an elevated temperature setpoint and an inability to retain body heat. GD (but not GC) rats also showed other effects previously seen in TSD rats, including debilitated appearance; severe ulcerative and hyperkeratotic lesions on the tails and plantar surfaces; initially increased and later decreased body temperature; decreased plasma thyroxine; increased triiodothyronine-thyroxine ratio; and eventual death. Evidently, NE-mediated sympathetic activation was not critical to any of these effects, although a role for catecholamines cannot be ruled out.

  3. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  4. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  5. Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF.

    Directory of Open Access Journals (Sweden)

    Keiko Miwa

    Full Text Available Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs and sympathetic neurons (SNs isolated from neonatal rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml or nerve growth factor (50 ng/ml. As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.

  6. Sympathetic Neurotransmitters and Tumor Angiogenesis—Link between Stress and Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jason Tilan

    2010-01-01

    Full Text Available Recent evidence supports a longstanding hypothesis that chronic stress can influence tumor growth and progression. It has been shown that sympathetic neurotransmitters, such as catecholamines and neuropeptides, can affect both cancer cell growth and tumor vascularization. Depending on neurotransmitter and type of tumor, these effects can be both stimulatory and inhibitory. Norepinephrine (NE and epinephrine (E are potent stimulators of vascularization, acting both by inducing the release of angiogenic factors from tumor cells and directly on endothelial cell (EC functions. As a result, activation of the adrenergic system increases growth of various types of tumors and has been shown to mediate stress-induced augmentation of tumor progression. Dopamine (DA, on the other hand, interferes with VEGF signaling in endothelial cells, blocks its angiogenic functions and inhibits tumor growth. Another sympathetic neurotransmitter coreleased with NE, neuropeptide Y (NPY, directly stimulates angiogenesis. However, proangiogenic actions of NPY can be altered by its direct effect on tumor cell proliferation and survival. In consequence, NPY can either stimulate or inhibit tumor growth, depending on tumor type. Hence, sympathetic neurotransmitters are powerful modulators of tumor growth and can become new targets in cancer therapy.

  7. Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function.

    Science.gov (United States)

    Bassi, Gabriel S; Brognara, Fernanda; Castania, Jaci A; Talbot, Jhimmy; Cunha, Thiago M; Cunha, Fernando Q; Ulloa, Luis; Kanashiro, Alexandre; Dias, Daniel P Martins; Salgado, Helio C

    2015-10-01

    The baroreflex is a critical physiological mechanism controlling cardiovascular function by modulating both the sympathetic and parasympathetic activities. Here, we report that electrical activation of the baroreflex attenuates joint inflammation in experimental arthritis induced by the administration of zymosan into the femorotibial cavity. Baroreflex activation combined with lumbar sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy dissected the mechanisms involved in the inflammatory modulation, highlighting the role played by sympathetic inhibition in the attenuation of joint inflammation. From the immunological standpoint, baroreflex activation attenuates neutrophil migration and the synovial levels of inflammatory cytokines including TNF, IL-1β and IL-6, but does not affect the levels of the anti-inflammatory cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the inhibition of the sympathetic drive to the knee. These results reveal a novel physiological neuronal network controlling peripheral local inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Examination of the Relationship between Psychosocial Mediators and Intervention Effects in It’s Your Game: An Effective HIV/STI/Pregnancy Prevention Intervention for Middle School Students

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    Elizabeth Baumler

    2012-01-01

    Full Text Available A set of mediation analyses were carried out in this study using data from It’s Your Game. . .Keep It Real (IYG, a successful HIV/STI/pregnancy prevention program. The IYG study evaluated a skill and normbased. HIV/STI/pregnancy prevention program that was implemented from 2004 to 2007 among 907 urban low-income middle school youth in Houston, TX, USA. Analyses were carried out to investigate the degree to which a set of proposed psychosocial measures of behavioral knowledge, perceived self-efficacy, behavioral, and normative beliefs, and perceived risky situations, all targeted by the intervention, mediated the intervention’s effectiveness in reducing initiation of sex. The mediation process was assessed by examining the significance and size of the estimated effects from the mediating pathways. The findings from this study provide evidence that the majority of the psychosocial mediators targeted by the IYG intervention are indeed related to the desired behavior and provide evidence that the conceptual theory underlying the targeted psychosocial mediators in the intervention is appropriate. Two of the psychosocial mediators significantly mediated the intervention effect, knowledge of STI signs and symptoms and refusal self-efficacy. This study suggests that the underlying causal mechanisms of action of these interventions are complex and warrant further analyses.

  9. Intimate Partner Violence, Sexual Autonomy and Postpartum STD Prevention Among Young Couples: A Mediation Analysis.

    Science.gov (United States)

    Willie, Tiara C; Callands, Tamora A; Kershaw, Trace S

    2018-03-01

    The transition to parenthood is a stressful time for young couples and can put them at risk for acquiring STDs. Mechanisms underlying this risk-particularly, intimate partner violence (IPV) and sexual autonomy-have not been well studied. Between 2007 and 2011, a prospective cohort study of the relationships and health of pregnant adolescents and their male partners recruited 296 couples at four hospital-based obstetrics and gynecology clinics in the U.S. Northeast; participants were followed up six and 12 months after the birth. Structural equation modeling identified associations among IPV at baseline and six months, sexual autonomy at six months and STD acquisition at 12 months. Mediating effects of sexual autonomy were tested via bootstrapping. Females were aged 14-21, and male partners were 14 or older. For females, IPV victimization at baseline was positively associated with the likelihood of acquiring a postpartum STD (coefficient, 0.4); level of sexual autonomy was inversely associated with the likelihood of acquiring an STD and of having a male partner who acquired one by the 12-month follow-up (-0.4 for each). For males, IPV victimization at baseline was negatively correlated with a female partner's sexual autonomy (-0.3) and likelihood of acquiring an STD (-0.7); victimization at six months was positively related to a partner's sexual autonomy (0.2). Sexual autonomy did not mediate these relationships. Females' sexual autonomy appears to protect against postpartum STDs for both partners. Future research should explore the efficacy of IPV-informed approaches to improving women's sexual and reproductive health. Copyright © 2018 by the Guttmacher Institute.

  10. Proprioceptive reflexes in patients with reflex sympathetic dystrophy.

    Science.gov (United States)

    Schouten, A C; Van de Beek, W J T; Van Hilten, J J; Van der Helm, F C T

    2003-07-01

    Reflex sympathetic dystrophy (RSD) is a syndrome that frequently follows an injury and is characterized by sensory, autonomic and motor features of the affected extremities. One of the more common motor features of RSD is tonic dystonia, which is caused by impairment of inhibitory interneuronal spinal circuits. In this study the circuits that modulate the gain of proprioceptive reflexes of the shoulder musculature are quantitatively assessed in 19 RSD patients, 9 of whom presented with dystonia. The proprioceptive reflexes are quantified by applying two types of force disturbances: (1) disturbances with a fixed low frequency and a variable bandwidth and (2) disturbances with a small bandwidth around a prescribed centre frequency. Compared to controls, patients have lower reflex gains for velocity feedback in response to the disturbances around a prescribed centre frequency. Additionally, patients with dystonia lack the ability to generate negative reflex gains for position feedback, for these same disturbances. Proprioceptive reflexes to the disturbances with a fixed low frequency and variable bandwidth present no difference between patients and controls. Although dystonia in the RSD patients was limited to the distal musculature, the results suggest involvement of interneuronal circuits that mediate postsynaptic inhibition of the motoneurons of the proximal musculature.

  11. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  12. Poly(ethylene glycol)-mediated conformational alteration of α-chymotrypsin prevents inactivation of insulin by stabilizing active intermediates.

    Science.gov (United States)

    Yu, Jibing; Wei, Xiuli; Zhang, Li; Fang, Xiaocui; Yang, Tao; Huang, Feng; Liang, Wei

    2014-10-06

    Proteolytic enzymes in the gut represent one of the biggest barriers against oral delivery of therapeutic proteins and peptides. In the current study, we explored the effect of poly(ethylene glycol) 400 (PEG 400), a commonly used crowding agent, on insulin degradation mediated by α-chymotrypsin (α-CT). Without PEG 400, insulin was quickly cleaved by α-CT to generate inactive degradation products. In comparison, incorporation of PEG 400 resulted in reaction mixtures with retained biological activity. The analysis on the conformation of α-CT and the local environment of the enzyme's active site unraveled that PEG 400 altered the conformation of α-CT to prevent the inactivation of insulin via stabilization of active intermediates. These findings indicated that PEG 400 may provide a promising addition toward oral delivery of insulin.

  13. White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer's Disease.

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    Mario F Mendez

    Full Text Available Resting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD and other frontally-predominant disorders.To identify the neuroanatomical correlates of skin conductance levels (SCLs, an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer's disease (AD, where it is not.This study analyzed bvFTD (n = 14 patients and a comparison group with early-onset AD (n = 19. We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging.As expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere.Among dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.

  14. Lymphocytic Meningitis in Patients with Sympathetic Ophthalmia.

    Science.gov (United States)

    Goudot, Mathilde; Groh, Matthieu; Salah, Sawsen; Monnet, Dominique; Blanche, Philippe; Brézin, Antoine P

    2017-04-01

    This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm 3 . The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.

  15. Sympathetic Nervous System Synchrony in Couple Therapy.

    Science.gov (United States)

    Karvonen, Anu; Kykyri, Virpi-Liisa; Kaartinen, Jukka; Penttonen, Markku; Seikkula, Jaakko

    2016-07-01

    The aim of this study was to test whether there is statistically significant sympathetic nervous system (SNS) synchrony between participants in couple therapy. To our knowledge, this is the first study to measure psychophysiological synchrony during therapy in a multiactor setting. The study focuses on electrodermal activity (EDA) in the second couple therapy session from 10 different cases (20 clients, 10 therapists working in pairs). The EDA concordance index was used as a measure of SNS synchrony between dyads, and synchrony was found in 85% of all the dyads. Surprisingly, co-therapists exhibited the highest levels of synchrony, whereas couples exhibited the lowest synchrony. The client-therapist synchrony was lower than that of the co-therapists, but higher than that of the couples. A Video Abstract is available next to the online version of this article on the JMFT web site. © 2016 American Association for Marriage and Family Therapy.

  16. Weight control and cancer preventive mechanisms: role of insulin growth factor-1-mediated signaling pathways.

    Science.gov (United States)

    Xie, Linglin; Wang, Weiqun

    2013-02-01

    Overweight and obese not only increase the risk of cardiovascular disease and type-2 diabetes mellitus, but are also now known risk factors for a variety of cancers. Weight control, via dietary calorie restriction and/or exercise, has been demonstrated to be beneficial for cancer prevention in various experimental models, but the underlying mechanisms are still not well defined. Recent studies conducted in a mouse skin carcinogenesis model show that weight loss induced a significant reduction of the circulating levels of insulin growth factor (IGF)-1 and other hormones, including insulin and leptin, resulting in reduced IGF-1-dependent signaling pathways, i.e. Ras-MAPK proliferation and protein kinase B-phosphoinositide 3-kinase (Akt-PI3K) antiapoptosis. Selective targeting IGF-1 to Akt/mammalian target of rapamycin and AMP-activated protein kinase pathways, via negative energy balance, might inactivate cell cycle progression and ultimately suppress tumor development. This review highlights the current studies focused on the major role of reducing IGF-1-activated signaling via weight control as a potential cancer preventive mechanism.

  17. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

    Directory of Open Access Journals (Sweden)

    Andrew Mamalis

    Full Text Available Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease.The goal of our study was to investigate the how reactive oxygen species (ROS free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed.High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR. For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2 on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2.High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched

  18. Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial damage mediated apoptosis in cardiomyoblasts.

    Science.gov (United States)

    Jadaun, Pratiksha; Yadav, Dhananjay; Bisen, Prakash Singh

    2018-04-01

    The current study was undertaken to study the effect of Spirulina platensis (Spirulina) extract on enhanced oxidative stress during high glucose induced cell death in H9c2 cells. H9c2 cultured under high glucose (33 mM) conditions resulted in a noteworthy increase in oxidative stress (free radical species) accompanied by loss of mitochondrial membrane potential, release of cytochrome c, increase in caspase activity and pro-apoptotic protein (Bax). Spirulina extract (1 μg/mL), considerably inhibited increased ROS and RNS levels, reduction in cytochrome c release, raise in mitochondrial membrane potential, decreased the over expression of proapoptotic protein Bax and suppressed the Bax/Bcl2 ratio with induced apoptosis without affecting cell viability. Overall results suggest that Spirulina extract plays preventing role against enhanced oxidative stress during high glucose induced apoptosis in cardiomyoblasts as well as related dysfunction in H9c2 cells.

  19. Glutamate and GABA in vestibulo-sympathetic pathway neurons

    Directory of Open Access Journals (Sweden)

    Gay R Holstein

    2016-02-01

    Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

  20. How did it work? Who did it work for? Mediation in the context of a moderated prevention effect for children of divorce.

    Science.gov (United States)

    Tein, Jenn-Yun; Sandler, Irwin N; MacKinnon, David P; Wolchik, Sharlene A

    2004-08-01

    This study presents a reanalysis of data from an effective preventive intervention for children from divorced families to test mediation of program effects. The study involved 157 children, age 9-12 years, who were randomly assigned to a parenting program or a literature control condition. Program effects to reduce posttest internalizing problems were mediated through improvement in mother-child relationship quality. Program effects to reduce externalizing problems at posttest and 6 months were mediated through improvement in posttest parental methods of discipline and mother-child relationship quality. The study also describes a new methodology to test mediation of Program x Baseline Status interactions. Analyses demonstrate mediation effects primarily for children who began the program with poorer scores on discipline, mother-child relationship quality, and externalizing problems.

  1. AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

    Directory of Open Access Journals (Sweden)

    Laia Vil

    2016-01-01

    Full Text Available Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1 specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1-Sirt1-treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. Moreover, SIRT1 overexpression in skeletal muscle also increased basal phosphorylated levels of AKT. However, AAV1-Sirt1 treatment was not enough to prevent high fat diet-induced obesity and insulin resistance. Although Sirt1 gene transfer to skeletal muscle induced changes at the muscular level related with lipid and glucose homeostasis, our data indicate that overexpression of SIRT1 in skeletal muscle is not enough to improve whole-body insulin resistance and that suggests that SIRT1 has to be increased in other metabolic tissues to prevent insulin resistance.

  2. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  3. A Technology-Mediated Behavioral Weight Gain Prevention Intervention for College Students: Controlled, Quasi-Experimental Study.

    Science.gov (United States)

    West, Delia Smith; Monroe, Courtney M; Turner-McGrievy, Gabrielle; Sundstrom, Beth; Larsen, Chelsea; Magradey, Karen; Wilcox, Sara; Brandt, Heather M

    2016-06-13

    Both men and women are vulnerable to weight gain during the college years, and this phenomenon is linked to an increased risk of several chronic diseases and mortality. Technology represents an attractive medium for the delivery of weight control interventions focused on college students, given its reach and appeal among this population. However, few technology-mediated weight gain prevention interventions have been evaluated for college students. This study examined a new technology-based, social media-facilitated weight gain prevention intervention for college students. Undergraduates (n =58) in two sections of a public university course were allocated to either a behavioral weight gain prevention intervention (Healthy Weight, HW; N=29) or a human papillomavirus (HPV) vaccination awareness intervention (control; N=29). All students were enrolled, regardless of initial body weight or expressed interest in weight management. The interventions delivered 8 lessons via electronic newsletters and Facebook postings over 9 weeks, which were designed to foster social support and introduce relevant educational content. The HW intervention targeted behavioral strategies to prevent weight gain and provided participants with a Wi-Fi-enabled scale and an electronic physical activity tracker to facilitate weight regulation. A repeated-measures analysis of variance was conducted to examine within- and between-group differences in measures of self-reported weight control practices and objectively measured weight. Use of each intervention medium and device was objectively tracked, and intervention satisfaction measures were obtained. Students remained weight stable (HW: -0.48+1.9 kg; control: -0.45+1.4 kg), with no significant difference between groups over 9 weeks (P =.94). However, HW students reported a significantly greater increase in the number of appropriate weight control strategies than did controls (2.1+4.5 vs -1.1+3.4, respectively; P =.003) and there was no increase in

  4. The role of sports clubs in helping older people to stay active and prevent frailty: a longitudinal mediation analysis.

    Science.gov (United States)

    Watts, Paul; Webb, Elizabeth; Netuveli, Gopalakrishnan

    2017-07-14

    Frailty is a common syndrome in older adults characterised by increased vulnerability to adverse health outcomes as a result of decline in functional and physiological measures. Frailty predicts a range of poor health and social outcomes and is associated with increased risk of hospital admission. The health benefits of sport and physical activity and the health risks of inactivity are well known. However, less is known about the role of sports clubs and physical activity in preventing and managing frailty in older adults. The objective of this study is to examine the role of membership of sports clubs in promoting physical activity and reducing levels of frailty in older adults. We used data from waves 1 to 7 of the English Longitudinal Study of Ageing (ELSA). Survey items on physical activity were combined to produce a measure of moderate or vigorous physical activity for each wave. Frailty was measured using an index of accumulated deficits. A total of sixty deficits, including symptoms, disabilities and diseases were recorded through self-report and tests. Direct and indirect relationships between sports club membership, levels of physical activity and frailty were examined using a cross-lagged panel model. We found evidence for an indirect relationship between sports club membership and frailty, mediated by physical activity. This finding was observed when examining time-specific indirect pathways and the total of all indirect pathways across seven waves of survey data (Est = -0.097 [95% CI = -0.124,-0.070], p = sports clubs may be useful in preventing and managing frailty in older adults, both directly and indirectly through increased physical activity levels. Sports clubs accessible to older people may improve health in this demographic by increasing activity levels and reducing frailty and associated comorbidities. There is a need for investment in these organisations to provide opportunities for older people to achieve the levels of physical activity

  5. Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

    Science.gov (United States)

    García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

    2012-06-07

    Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

  6. Effect of generalised sympathetic activation by cold pressor test on cerebral haemodynamics in healthy humans.

    Science.gov (United States)

    Roatta, S; Micieli, G; Bosone, D; Losano, G; Bini, R; Cavallini, A; Passatore, M

    1998-07-15

    There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.

  7. Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals

    Science.gov (United States)

    Prajapati, Saumya; Tao, Jinhui; Ruan, Qichao; De Yoreo, James J.; Moradian-Oldak, Janet

    2015-01-01

    Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair. PMID:26513418

  8. Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss.

    Science.gov (United States)

    Choo, Young-Yeon; Tran, Phuong Thao; Min, Byung-Sun; Kim, Okwha; Nguyen, Hai Dang; Kwon, Seung-Hae; Lee, Jeong-Hyung

    2017-11-01

    Receptor activator of nuclear factor-kB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Suppressing osteoclastogenesis is considered an effective therapeutic approach for bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Sappanone A (SPNA), a homoisoflavanone compound isolated from the heartwood of Caesalpinia sappan, has been reported to exert anti-inflammatory effects; however, the effects of SPNA on osteoclastogenesis have not been investigated. In the present study, we describe for the first time that SPNA inhibits RANKL-induced osteoclastogenesis in mouse bone marrow macrophages (BMMs) and suppresses inflammation-induced bone loss in a mouse model. SPNA inhibited the formation of osteoclasts from BMMs, osteoclast actin-ring formation, and bone resorption in a concentration-dependent manner. At the molecular level, SPNA significantly inhibited RANKL-induced activation of the AKT/glycogen synthase kinase-3β (GSK-3β) signaling pathway without affecting its activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK. In addition, SPNA suppressed the induction of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is a crucial transcription factor in osteoclast differentiation. As a result, SPNA decreased osteoclastogenesis-related marker gene expression, including CtsK, TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), MMP-9 and osteoclast-associated receptor (OSCAR). In a mouse inflammatory bone loss model, SPNA significantly inhibited lipopolysaccharide (LPS)-induced bone loss by suppressing the number of osteoclasts. Taken together, these findings suggest that SPNA inhibits osteoclastogenesis and bone resorption by inhibiting the AKT/GSK-3β signaling pathway and may be a potential candidate compound for the prevention and/or treatment of inflammatory bone loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals.

    Science.gov (United States)

    Prajapati, Saumya; Tao, Jinhui; Ruan, Qichao; De Yoreo, James J; Moradian-Oldak, Janet

    2016-01-01

    Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Pseudodystrophy. A conversion disorder mimicking reflex sympathetic dystrophy.

    Science.gov (United States)

    Driessens, M; Blockx, P; Geuens, G; Dijs, H; Verheyen, G; Stassijns, G

    2002-10-01

    The authors suggest some criteria by which pseudodystrophy and reflex sympathetic dystrophy, although sharing some similar clinical features, can be distinguished as two different conditions, each requiring its own approach and management. The most important distinction is found on bone scintigraphy. In reflex sympathetic dystrophy the bone scan shows a typical increased tracer uptake (at least during stages I and II); in pseudodystrophy there is a normal or decreased tracer uptake in the affected region. Moreover the vascularization is increased in reflex sympathetic dystrophy stage I, whereas in pseudodystrophy hypovascularization is found from the beginning. The clinical features, as well as the results of technical investigations, psychological evaluation and treatment of 4 patients with pseudodystrophy are presented. The importance of distinguishing this condition from reflex sympathetic dystrophy is stressed.

  11. Cardiovascular Response Patterns to Sympathetic Stimulation by Central Hypovolemia

    NARCIS (Netherlands)

    Bronzwaer, Anne-Sophie G. T.; Verbree, Jasper; Stok, Wim J.; van Buchem, Mark A.; Daemen, Mat J. A. P.; van Osch, Matthias J. P.; van Lieshout, Johannes J.

    2016-01-01

    In healthy subjects, variation in cardiovascular responses to sympathetic stimulation evoked by submaximal lower body negative pressure (LBNP) is considerable. This study addressed the question whether inter-subject variation in cardiovascular responses coincides with consistent and reproducible

  12. Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.

    Science.gov (United States)

    Coates, Alexandra M; Incognito, Anthony V; Seed, Jeremy D; Doherty, Connor J; Millar, Philip J; Burr, Jamie F

    2018-05-01

    Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P 0.05). Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.

  13. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

    Science.gov (United States)

    Arnold, Julia; Barcena de Arellano, Maria L; Rüster, Carola; Vercellino, Giuseppe F; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

    2012-01-01

    To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Schwanomma From Cervical Sympathetic Chain Ganglion – A Rare Presentation

    Science.gov (United States)

    Asma, A. Affee

    2015-01-01

    Schwanommas arising from cervical sympathetic chain are tumours that are rare in occurrence. These lesions are usually difficult to differentiate from a vagal schwanomma and a carotid body tumour during the initial workup. In this report, a rarely seen huge cervical sympathetic chain schwanomma case with partial Horner’s syndrome is being presented in detail, which to our known knowledge, is one of the few cases reported in literature. PMID:26557566

  15. Schwanomma From Cervical Sympathetic Chain Ganglion - A Rare Presentation.

    Science.gov (United States)

    Asma, A Affee; Kannah, E

    2015-10-01

    Schwanommas arising from cervical sympathetic chain are tumours that are rare in occurrence. These lesions are usually difficult to differentiate from a vagal schwanomma and a carotid body tumour during the initial workup. In this report, a rarely seen huge cervical sympathetic chain schwanomma case with partial Horner's syndrome is being presented in detail, which to our known knowledge, is one of the few cases reported in literature.

  16. Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

    Science.gov (United States)

    2012-04-26

    reviewed and approved by the US Army Medical Research and Materiel Command Institutional Review Board and in accor- dance with the approved protocols...C. (2007b). Sympathetic nerve activity and heart rate vari- ability during severe hemorrhagic shock in sheep.Auton. Neurosci . 136, 43–51. Billman, G...A. (2002). Syncopal attack alters the burst properties of muscle sympathetic nerve activity in humans. Auton. Neurosci . 95, 141–145. Iwase, S

  17. [Regional transient osteoporosis, and reflex sympathetic dystrophy: the same disease?].

    Science.gov (United States)

    Castellano, Karina; Plantalech, Luisa

    2005-01-01

    Complex regional pain syndrome, reflex sympathetic dystrophy, regional, transient and migratory osteoporosis, are known as a spectrum of medical conditions that present with pain, edema, erythema, localized osteoporosis and sometimes sympathetic dysfunction. Many factors which are present in these conditions, such as clinical presentation, radiologic findings and a variety of still unclear physiopathologic mechanisms are correlated. We propose that all these conditions are different periods of the same pathology.

  18. Current management of reflex sympathetic dystrophy syndrome (complex regional pain syndrome type I).

    Science.gov (United States)

    Berthelot, Jean-Marie

    2006-10-01

    Although no major advances have occurred in the curative treatment of reflex sympathetic dystrophy syndrome (RSDS), new pathogenic insights may soon lead to innovative approaches, which may also prove effective in alleviating some forms of neuropathic pain. Preventing nerve compression and ischemia-reperfusion injury constitute valuable measures for preventing RSDS. Vitamin C administration can also prevent RSDS, together with clonidine in high-risk patients. Short-term glucocorticoid therapy has been found effective in preventing RSDS after stroke but has not been evaluated in other situations. Beneficial effects of bisphosphonates have been documented in several placebo-controlled trials. Placebo-controlled trials of ketamine and spinal cord stimulation are in order to confirm or refute the promising results obtained in open-label studies. Mirror visual feedback was introduced recently for the rehabilitation of patients with RSDS but needs to be evaluated in randomized controlled trials.

  19. Mediating Factors of a School-Based Multi-Component Smoking Prevention Intervention: The LdP Cluster Randomized Controlled Trial

    Science.gov (United States)

    Carreras, G.; Bosi, S.; Angelini, P.; Gorini, G.

    2016-01-01

    The aim of this study was to investigate factors mediating the effects of Luoghi di Prevenzione (LdP) smoking prevention intervention based on social competence and social influence approaches, and characterized by peer-led school-based interventions, out-of-school workshops, school lessons, and by enforcing the school anti-smoking policy.…

  20. Testing Mediators Hypothesized to Account for the Effects of a Dissonance-Based Eating Disorder Prevention Program over Longer Term Follow-Up

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather

    2011-01-01

    Objective: Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method: Data were drawn from a randomized effectiveness trial in which 306 female high school students…

  1. Doppler sonographic assessment of posttraumatic reflex sympathetic dystrophy.

    Science.gov (United States)

    Pekindil, Gökhan; Pekindil, Yesim; Sarikaya, Ali

    2003-04-01

    To reveal the arterial Doppler sonographic findings in cases of posttraumatic reflex sympathetic dystrophy Eleven patients had hand reflex sympathetic dystrophy, and 9 had foot reflex sympathetic dystrophy. The duration of symptoms ranged from 1 to 28 weeks, and the history of fracture ranged from 6 to 48 weeks. Bilateral brachial or popliteal arteries proximal to injuries were evaluated by Doppler sonography with a 7.5-MHz linear transducer. All patients also had triphasic bone scintigraphy and extremity thermography Two patients had monophasic waveforms and 4 had low-pulsatility triphasic waveforms on the affected limbs when compared with the asymptomatic limbs. All opposite asymptomatic limbs had normal triphasic waveforms in these 6 cases. Spectral analysis revealed a loss or decrease of a normal reversed flow component with a reduced pulsatility index on the affected limb. Fourteen other patients had symmetric triphasic waveforms. We observed that the patients who had stage 1 reflex sympathetic dystrophy and warm limbs with durations of symptoms of more than 2 weeks had positive Doppler sonographic findings, whereas all patients with stage 2 reflex sympathetic dystrophy and all with normal skin temperature, regardless of stage, had normal waveforms. Doppler sonography revealed loss of normal triphasic arterial waveforms in some of the cases of stage 1 disease, whereas many cases of stage 1 disease and all cases of stage 2 disease had normal findings. Therefore, we think that Doppler sonography cannot be used for the diagnosis of reflex sympathetic dystrophy but may help in assessing hemodynamic stages of the disease.

  2. Hysteresis in the sympathetic baroreflex: role of baseline nerve activity

    Science.gov (United States)

    Hart, Emma C; Wallin, B Gunnar; Curry, Timothy B; Joyner, Michael J; Karlsson, Tomas; Charkoudian, Nisha

    2011-01-01

    Abstract Sympathetic baroreflex sensitivity (BRS) is greater during decreasing compared to increasing diastolic blood pressure (DBP) in young men and women. In older men and women there is no difference in sympathetic BRS to increasing and decreasing DBP. We investigated whether the sensitivity of the central nervous system to increasing and decreasing DBP is dependent upon baseline muscle sympathetic nerve activity (MSNA). We hypothesised that the difference in sympathetic BRS between falling and rising segments of DBP would be positively related to baseline MSNA in 30 young men, 21 young women, 14 older men and 14 postmenopausal women. MSNA was measured using peroneal microneurography and BRS was measured using the spontaneous baroreflex threshold technique. On average, sympathetic BRS was greater during decreasing compared to increasing DBP in young men (P 0.05). In summary, baseline MSNA plays a role in determining sympathetic BRS to falling and rising DBP in young and older men and postmenopausal women, but not in young women. This relationship is consistent with a decreased potential for sympathoexcitation in people with higher resting MSNA. Furthermore, the lack of relationship in young women suggests important contributions of sex hormones to differential responses of MSNA to falling and rising pressures. PMID:21540345

  3. NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention.

    Science.gov (United States)

    McCarty, Mark F

    2015-04-15

    Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways-exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine-which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine-mediate this benefit. Ameliorating the risk factors for SVD-including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine-also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

  4. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice.

    Science.gov (United States)

    Halliday, Mark; Radford, Helois; Zents, Karlijn A M; Molloy, Collin; Moreno, Julie A; Verity, Nicholas C; Smith, Ewan; Ortori, Catharine A; Barrett, David A; Bushell, Martin; Mallucci, Giovanna R

    2017-06-01

    See Mercado and Hetz (doi:10.1093/brain/awx107) for a scientific commentary on this article.Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer’s disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss. Re-establishing translation rates by inhibition of eIF2α-P activity, genetically or pharmacologically, restores memory and prevents neurodegeneration and extends survival. However, the experimental compounds used preclinically are unsuitable for use in humans, due to associated toxicity or poor pharmacokinetic properties. To discover compounds that have anti-eIF2α-P activity suitable for clinical use, we performed phenotypic screens on a NINDS small molecule library of 1040 drugs. We identified two compounds, trazodone hydrochloride and dibenzoylmethane, which reversed eIF2α-P-mediated translational attenuation in vitro and in vivo. Both drugs were markedly neuroprotective in two mouse models of neurodegeneration, using clinically relevant doses over a prolonged period of time, without systemic toxicity. Thus, in prion-diseased mice, both trazodone and dibenzoylmethane treatment restored memory deficits, abrogated development of neurological signs, prevented neurodegeneration and significantly prolonged survival. In tauopathy-frontotemporal dementia mice, both drugs were neuroprotective, rescued memory deficits and reduced hippocampal atrophy. Further, trazodone reduced p-tau burden. These compounds therefore represent potential new disease-modifying treatments for dementia. Trazodone in particular, a licensed drug, should

  5. Visceral afferent activation-induced changes in sympathetic nerve activity and baroreflex sensitivity.

    Science.gov (United States)

    Saleh, T M; Connell, B J; Allen, G V

    1999-06-01

    The following experiments were done to determine whether changes in baroreflex sensitivity evoked by cervical vagus nerve stimulation are due to sympathoexcitation mediated by the parabrachial nucleus. The relative contribution of cardiopulmonary and general gastric afferents within the cervical vagus nerve to the depression in baroreflex sensitivity are also investigated. Male Sprague-Dawley rats anesthetized with thiobutabarbital sodium (50 mg/kg) were instrumented to measure blood pressure and heart rate or for the continuous monitoring of renal sympathetic nerve activity. Baroreflex sensitivity was measured using bolus injections of phenylephrine. Electrical stimulation of the cervical vagus (with or without the aortic depressor nerve) or the abdominal vagus nerve produced a significant increase in renal nerve activity and a decrease in baroreflex sensitivity. Both of these effects were blocked after the microinjection of lidocaine into the parabrachial nucleus before nerve stimulation. Therefore, we conclude that an increase in the activity of cardiac, pulmonary, or general gastric afferents mediated the increased sympathetic output and decreased baroreflex sensitivity via a pathway involving the parabrachial nucleus.

  6. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

    Science.gov (United States)

    Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

    2015-01-01

    Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

  7. Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords

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    Chun-Kuei Su

    2018-03-01

    Full Text Available Nitric oxide (NO is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM. NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors, indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker, gabazine (a GABAA receptor blocker, or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor

  8. Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords.

    Science.gov (United States)

    Su, Chun-Kuei; Chen, Yi-Yin; Ho, Chiu-Ming

    2018-01-01

    Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM). NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors), indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker), gabazine (a GABA A receptor blocker), or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker) also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor) pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor activities were found

  9. HIF2A and IGF2 Expression Correlates in Human Neuroblastoma Cells and Normal Immature Sympathetic Neuroblasts

    Directory of Open Access Journals (Sweden)

    Sofie Mohlin

    2013-03-01

    Full Text Available During normal sympathetic nervous system (SNS development, cells of the ganglionic lineage can malignantly transform and develop into the childhood tumor neuroblastoma. Hypoxia-inducible transcription factors (HIFs mediate cellular responses during normal development and are central in the adaptation to oxygen shortage. HIFs are also implicated in the progression of several cancer forms, and high HIF-2α expression correlates with disseminated disease and poor outcome in neuroblastoma. During normal SNS development, HIF2A is transiently expressed in neuroblasts and chromaffin cells. SNS cells can, during development, be distinguished by distinct gene expression patterns, and insulin-like growth factor 2 (IGF2 is a marker of sympathetic chromaffin cells, whereas sympathetic neuroblasts lack IGF2 expression. Despite the neuronal derivation of neuroblastomas, we show that neuroblastoma cell lines and specimens express IGF2 and that expression of HIF2A and IGF2 correlates, with the strongest correlation in high-stage tumors. In neuroblastoma, both IGF2 and HIF2A are hypoxia-driven and knocking down IGF2 at hypoxia resulted in downregulated HIF2A levels. HIF-2α and IGF2 were strongly expressed in subsets of immature neuroblastoma cells, suggesting that these two genes could be co-expressed also at early stages of SNS development. We show that IGF2 is indeed expressed in sympathetic chain ganglia at embryonic week 6.5, a developmental stage when HIF-2α is present. These findings provide a rationale for the unexpected IGF2 expression in neuroblastomas and might suggest that IGF2 and HIF2A positive neuroblastoma cells are arrested at an embryonic differentiation stage corresponding to the stage when sympathetic chain ganglia begins to coalesce.

  10. Acute inhibition of glial cells in the NTS does not affect respiratory and sympathetic activities in rats exposed to chronic intermittent hypoxia.

    Science.gov (United States)

    Costa, Kauê M; Moraes, Davi J A; Machado, Benedito H

    2013-02-16

    Recent studies suggest that neuron-glia interactions are involved in multiple aspects of neuronal activity regulation. In the nucleus tractus solitarius (NTS) neuron-glia interactions are thought to participate in the integration of autonomic responses to physiological challenges. However, it remains to be shown whether NTS glial cells might influence breathing and cardiovascular control, and also if they could be integral to the autonomic and respiratory responses to hypoxic challenges. Here, we investigated whether NTS glia play a tonic role in the modulation of central respiratory and sympathetic activities as well as in the changes in respiratory-sympathetic coupling induced by exposure to chronic intermittent hypoxia (CIH), a model of central autonomic and respiratory plasticity. We show that bilateral microinjections of fluorocitrate (FCt), a glial cell inhibitor, into the caudal and intermediate subnuclei of the NTS did not alter baseline respiratory and sympathetic parameters in in situ preparations of juvenile rats. Similar results were observed in rats previously exposed to CIH. Likewise, CIH-induced changes in respiratory-sympathetic coupling were unaffected by FCt-mediated inhibition. However, microinjection of FCt into the ventral medulla produced changes in respiratory frequency. Our results show that acute glial inhibition in the NTS does not affect baseline respiratory and sympathetic control. Additionally, we conclude that NTS glial cells may not be necessary for the continuous manifestation of sympathetic and respiratory adaptations to CIH. Our work provides evidence that neuron-glia interactions in the NTS do not participate in baseline respiratory and sympathetic control. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

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    Hui Chen

    2013-11-01

    Full Text Available Background/Aims: Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects. Methods: Eplerenone (a selective aldosterone blocker or vehicle (control, was given to male Wistar rats (50 mg/kg, twice daily for 7 days before unilateral ureteral obstruction (UUO and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immune-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, α-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery. Results: Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration, interstitial cell proliferation, and activation of interstitial cells (α-SMA expression. Epleronone also reduced oxidative stress. Conclusion: The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress.

  12. An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2013-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia. Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications, the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction. This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

  13. Testing Mediators Hypothesized to Account for the Effects of a Dissonance Eating Disorder Prevention Program Over Longer-Term Follow-Up

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather

    2011-01-01

    Objective Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method Data were drawn from a randomized effectiveness trial in which 306 female high school students (M age = 15.7 SD = 1.1) with body image concerns were randomized to the 4-session dissonance-based prevention program or an educational brochure control condition, wherein school counselors and nurses were responsible for participant recruitment and intervention delivery. Results Dissonance participants showed greater reductions in thin-ideal internalization, body dissatisfaction, and eating disorder symptoms; change in thin-ideal internalization predicted change in body dissatisfaction and symptoms; change in body dissatisfaction predicted change in symptoms; and all indirect effects were significant. Change in thin-ideal internalization fully mediated the effects of intervention condition on change in body dissatisfaction and partially mediated the effects on symptoms; change in body dissatisfaction partially mediated the effect of intervention condition on change in symptoms. Conclusions Findings provided support for the intervention theory of this eating disorder prevention program over longer-term follow-up, extending the evidence base for this effective intervention. PMID:21500884

  14. Sympathetic cooling of ytterbium with rubidium

    International Nuclear Information System (INIS)

    Tassy, S.

    2007-01-01

    Within the scope of this thesis, a mixture of ultracold ytterbium and rubidium atoms was experimentally realized and investigated. For these experiments, a novel trap geometry was developed which allows simultaneous trapping and cooling of diamagnetic and paramagnetic atomic species. The main focus was put on the investigation of the interspecies scattering properties, where sympathetic cooling of ytterbium through elastic collisions with rubidium could be demonstrated. In addition, the interspecies scattering length could be determined. In the current configuration the combined trap allows the preparation of up to 2.10 5 atoms of 170 Yb, 171 Yb, 172 Yb, 174 Yb or 176 Yb at a temperature of 40..60 μK and a density in the range of 10 12 cm -3 , and of about 10 7 87 Rb atoms at a temperature of 25 μK and a density in the range of 5.10 11 cm -3 . Detailed studies of the thermalization of bosonic 170 Yb, 172 Yb, 174 Yb and 176 Yb and of fermionic 171 Yb each with 87 Rb were performed under varying experimental conditions. The deduced total scattering cross section was clearly found to increase with higher mass of the ytterbium isotope. In general, a mass scaling of the scattering properties is in agreement with theoretical models and former experimental work. With the assumption of pure s-wave scattering, which is approximately fulfilled for the given experimental parameters, the interspecies scattering length could be derived from the measured thermalization data and was found to be (in units of the Bohr radius a 0 ): 170 Yb- 87 Rb:(18 +12 -4 )a 0 , 171 Yb- 87 Rb:(25 +14 -7 )a 0 , 172 Yb- 87 Rb:(33 +23 -7 )a 0 , 174 Yb- 87 Rb:(83 +89 -25 )a 0 , 176 Yb- 87 Rb:(127 +245 -45 )a 0 . (orig./HSI)

  15. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome

    Science.gov (United States)

    Adami, S; Fossaluzza, V; Gatti, D; Fracassi, E; Braga, V

    1997-01-01

    OBJECTIVE—The reflex sympathetic dystrophy syndrome (RSDS) is a painful limb disorder, for which a consistently effective treatment has not yet been identified. The disease is associated with increased bone resorption and patchy osteoporosis, which might benefit from treatment with bisphosphonates, powerful inhibitors of bone resorption.
METHODS—Twenty patients with RSDS of foot and hand, were randomly assigned to blind administration of either alendronate intravenously (Istituto Gentili, Pisa, Italy) 7.5 mg dissolved in 250 ml saline solution or placebo saline infusions daily for three days. Two weeks later all patients had an identical treatment course with open labelled alendronate (7.5 mg/day for three days), independent from the results of the first blind treatment.
RESULTS—In the patients treated with blind alendronate the diminution in spontaneous pain, tenderness, and swelling (circumference of the affected limb) and the improvement in motion were significantly different from baseline (p<0.001), from those observed within the first two weeks in the control group (p<0.01), and from week 2 to week 4 (p<0.01). In the patients given blind placebo infusions no relevant symptomatic changes were observed after the first two weeks of follow up, but they responded to the open alendronate therapy given afterwards. In 12 patients with RSDS of the hand the ultradistal bone mineral content (BMC) of the affected arm was considerably lower than that of the controlateral arm (mean (SD)) (426(82) mg/cm versus 688(49)). Six weeks after the beginning of the trial BMC rose by 77(12) mg/cm (p<0.001) in the affected arm, but it did not change in the controlateral.
CONCLUSIONS—These results indicate that bisphosphonates should be considered for the treatment of RSDS, producing consistent and rapid remission of the disease.

 PMID:9135227

  16. The mediational role of neurocognition in the behavioral outcomes of a social-emotional prevention program in elementary school students: effects of the PATHS Curriculum.

    Science.gov (United States)

    Riggs, Nathaniel R; Greenberg, Mark T; Kusché, Carol A; Pentz, Mary Ann

    2006-03-01

    Neuropsychology is one field that holds promise in the construction of comprehensive, developmental models for the promotion of social competence and prevention of problem behavior. Neuropsychological models of behavior suggest that children's neurological functioning affects the regulation of strong emotions, as well as performance in social, cognitive, and behavioral spheres. The current study examines the underlying neurocognitive conceptual theory of action of one social-emotional development program. Hypothesized was that inhibitory control and verbal fluency would mediate the relationship between program condition and teacher-reported externalizing and internalizing behavior problems. Participants were 318 regular education students enrolled in the second or third grade. A series of regression analyses provided empirical support for (a) the effectiveness of the PATHS Curriculum in promoting inhibitory control and verbal fluency and (b) a partial mediating role for inhibitory control in the relation between prevention condition and behavioral outcomes. Implications are that programs designed to promote social and emotional development should consider comprehensive models that attend to neurocognitive functioning and development. Lack of consideration of neurocognitive pathways to the promotion of social competence may ignore important mechanisms through which prevention affects youth outcomes. Furthermore, the findings suggest that developers of social-emotional preventions should design curricula to explicitly promote the developmental integration of executive functioning, verbal processing, and emotional awareness. Doing so may enhance prevention outcomes particularly if those preventions are implemented during a time of peak neurocognitive development.

  17. [MRI symptomology in reflex sympathetic dystrophy of the foot].

    Science.gov (United States)

    Darbois, H; Boyer, B; Dubayle, P; Lechevalier, D; David, H; Aït-Ameur, A

    1999-08-01

    To describe the MRI findings of reflex sympathetic dystrophy of the foot and ankle. Retrospective study of 50 patients with reflex sympathetic dystrophy of the foot (5 with the cold form, and 45 with the warm form) diagnosed based on clinical and scintigraphic findings. All patients underwent MR imaging. The MRI findings were correlated with the clinical and scintigraphic findings. Patients with the cold form of reflex sympathetic dystrophy had no abnormality of signal at MR imaging. All patients with the warm from of reflex sympathetic dystrophy showed periarticular marrow edema at MR, typically involving more than one bone (mean of 4). Other findings were inconstant: soft tissue edema, joint effusion, and rarely, subchondral band of low T1W signal intensity of unclear etiology. MR imaging, including fat-suppressed T2W or STIR images and noncontrast T1W images, is helpful in patients with the warm or acute form of reflex sympathetic dystrophy of the foot. In patients with the cold form, MR imaging is helpful to exclude another underlying etiology for the symptoms and identify patients with the warm form of the process.

  18. Mindfulness meditation lowers muscle sympathetic nerve activity and blood pressure in African-American males with chronic kidney disease.

    Science.gov (United States)

    Park, Jeanie; Lyles, Robert H; Bauer-Wu, Susan

    2014-07-01

    Mindfulness meditation (MM) is a stress-reduction technique that may have real biological effects on hemodynamics but has never previously been tested in chronic kidney disease (CKD) patients. In addition, the mechanisms underlying the potential blood pressure (BP)-lowering effects of MM are unknown. We sought to determine whether MM acutely lowers BP in CKD patients, and whether these hemodynamic changes are mediated by a reduction in sympathetic nerve activity. In 15 hypertensive African-American (AA) males with CKD, we conducted a randomized, crossover study in which participants underwent 14 min of MM or 14 min of BP education (control intervention) during two separate random-order study visits. Muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, heart rate (HR), and respiratory rate (RR) were continuously measured at baseline and during each intervention. A subset had a third study visit to undergo controlled breathing (CB) to determine whether a reduction in RR alone was sufficient in exacting hemodynamic changes. We observed a significantly greater reduction in systolic BP, diastolic BP, mean arterial pressure, and HR, as well as a significantly greater reduction in MSNA, during MM compared with the control intervention. Participants had a significantly lower RR during MM; however, in contrast to MM, CB alone did not reduce BP, HR, or MSNA. MM acutely lowers BP and HR in AA males with hypertensive CKD, and these hemodynamic effects may be mediated by a reduction in sympathetic nerve activity. RR is significantly lower during MM, but CB alone without concomitant meditation does not acutely alter hemodynamics or sympathetic activity in CKD.

  19. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

    Science.gov (United States)

    Raffel, D M; Corbett, J R; del Rosario, R B; Gildersleeve, D L; Chiao, P C; Schwaiger, M; Wieland, D M

    1996-12-01

    The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

  20. Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients.

    Science.gov (United States)

    Metzler-Wilson, Kristen; Toma, Kumika; Sammons, Dawn L; Mann, Sarah; Jurovcik, Andrew J; Demidova, Olga; Wilson, Thad E

    2015-09-01

    Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm(-2)·min(-1), P rosacea and controls, respectively) stress was augmented in rosacea (both P rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component. Copyright © 2015 the American Physiological Society.

  1. How is chronic pain related to sympathetic dysfunction and autonomic dysreflexia following spinal cord injury?

    Science.gov (United States)

    Walters, Edgar T

    2018-01-01

    Autonomic dysreflexia (AD) and neuropathic pain occur after severe injury to higher levels of the spinal cord. Mechanisms underlying these problems have rarely been integrated in proposed models of spinal cord injury (SCI). Several parallels suggest significant overlap of these mechanisms, although the relationships between sympathetic function (dysregulated in AD) and nociceptive function (dysregulated in neuropathic pain) are complex. One general mechanism likely to be shared is central sensitization - enhanced responsiveness and synaptic reorganization of spinal circuits that mediate sympathetic reflexes or that process and relay pain-related information to the brain. Another is enhanced sensory input to spinal circuits caused by extensive alterations in primary sensory neurons. Both AD and SCI-induced neuropathic pain are associated with spinal sprouting of peptidergic nociceptors that might increase synaptic input to the circuits involved in AD and SCI pain. In addition, numerous nociceptors become hyperexcitable, hypersensitive to chemicals associated with injury and inflammation, and spontaneously active, greatly amplifying sensory input to sensitized spinal circuits. As discussed with the aid of a preliminary functional model, these effects are likely to have mutually reinforcing relationships with each other, and with consequences of SCI-induced interruption of descending excitatory and inhibitory influences on spinal circuits, with SCI-induced inflammation in the spinal cord and in DRGs, and with activity in sympathetic fibers within DRGs that promotes local inflammation and spontaneous activity in sensory neurons. This model suggests that interventions selectively targeting hyperactivity in C-nociceptors might be useful for treating chronic pain and AD after high SCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  3. Antiallodynic Effect of Pregabalin in Rat Models of Sympathetically Maintained and Sympathetic Independent Neuropathic Pain

    Science.gov (United States)

    Han, Dong Woo; Kweon, Tae Dong; Lee, Jong Seok

    2007-01-01

    Pregabalin binds to the voltage-dependent calcium channel α2δ subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 & L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The α2δ subunit might be less involved in the CA in SIP. PMID:17326244

  4. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-01-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal

  5. Propranolol for Paroxysmal Sympathetic Hyperactivity with Lateralizing Hyperhidrosis after Stroke

    Directory of Open Access Journals (Sweden)

    Jason W. Siefferman

    2015-01-01

    Full Text Available Brain injury can lead to impaired cortical inhibition of the hypothalamus, resulting in increased sympathetic nervous system activation. Symptoms of paroxysmal sympathetic hyperactivity may include hyperthermia, tachycardia, tachypnea, vasodilation, and hyperhidrosis. We report the case of a 41-year-old man who suffered from a left middle cerebral artery stroke and subsequently developed central fever, contralateral temperature change, and hyperhidrosis. His symptoms abated with low-dose propranolol and then returned upon discontinuation. Restarting propranolol again stopped his symptoms. This represents the first report of propranolol being used for unilateral dysautonomia after stroke. Propranolol is a lipophilic nonselective beta-blocker which easily crosses the blood-brain barrier and may be used to treat paroxysmal sympathetic hyperactivity.

  6. Effect of ghrelin on regulation of splenic sympathetic nerve discharge.

    Science.gov (United States)

    Balivada, Sivasai; Pawar, Hitesh N; Montgomery, Shawnee; Kenney, Michael J

    2016-12-01

    Ghrelin influences immune system function and modulates the sympathetic nervous system; however, the contribution of ghrelin to neural-immune interactions is not well-established because the effect of ghrelin on splenic sympathetic nerve discharge (SND) is not known. This study tested the hypothesis that central ghrelin administration would inhibit splenic SND in anesthetized rats. Rats received intracerebroventricular (ICV) injections of ghrelin (1nmol/kg) or aCSF. Lumbar SND recordings provided a non-visceral nerve control. The ICV ghrelin administration significantly increased splenic and lumbar SND, whereas mean arterial pressure (MAP) was not altered. These findings provide fundamental information regarding the nature of sympathetic-immune interactions. Published by Elsevier B.V.

  7. Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones

    Science.gov (United States)

    Fernandez-Fernandez, Jose M; Wanaverbecq, Nicolas; Halley, Pam; Caulfield, Malcolm P; Brown, David A

    1999-01-01

    G protein-regulated inward rectifier K+ (GIRK) channels were over-expressed in dissociated rat superior cervical sympathetic (SCG) neurones by co-transfecting green fluorescent protein (GFP)-, GIRK1- and GIRK2-expressing plasmids using the biolistic technique. Membrane currents were subsequently recorded with whole-cell patch electrodes.Co-transfected cells had larger Ba2+-sensitive inwardly rectifying currents and 13 mV more negative resting potentials (in 3 mm[K+]o) than non-transfected cells, or cells transfected with GIRK1 or GIRK2 alone.Carbachol (CCh, 1–30 μm) increased the inwardly rectifying current in 70% of GIRK1+ GIRK2-transfected cells by 261 ± 53% (n = 6, CCh 30 μm) at −120 mV, but had no effect in non-transfected cells or in cells transfected with GIRK1 or GIRK2 alone. Pertussis toxin prevented the effect of carbachol but had no effect on basal currents.The effect of CCh was antagonized by 6 nm tripitramine but not by 100 nm pirenzepine, consistent with activation of endogenous M2 muscarinic acetylcholine receptors.In contrast, inhibition of the voltage-activated Ca2+ current by CCh was antagonized by 100 nm pirenzepine but not by 6 nm tripitramine, indicating that it was mediated by M4 muscarinic acetylcholine receptors.We conclude that endogenous M2 and M4 muscarinic receptors selectively couple to GIRK currents and Ca2+ currents respectively, with negligible cross-talk. PMID:10066893

  8. Bursting into space: alterations of sympathetic control by space travel

    Science.gov (United States)

    Eckberg, D. L.

    2003-01-01

    AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

  9. [Reflex sympathetic dystrophy: description of a case with skin lesions].

    Science.gov (United States)

    Vergara, Aránzazu; Isarría, María J; Prado Sánchez-Caminero, María; Guerra, Aurora

    2005-10-01

    Reflex sympathetic dystrophy or algodystrophy is a poorly defined syndrome in which the patient develops pain disproportionate to the cause. It is included among the complex regional pain syndromes. The symptoms are triggered by some type of trauma, at times trivial, and consist of burning pain, edema, changes in skin color, alterations in vascularization, temperature changes, hyperhidrosis and skin disorders, which primarily consist of atrophic changes. Other less frequent cutaneous manifestations have been described in patients with this syndrome. These include papules, blisters, inflammatory lesions and reticulated hyperpigmentation. We discuss the case of a patient with reflex sympathetic dystrophy who presented with superficial ulcers on the affected limb, which mimicked dermatitis artefacta.

  10. Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN

    Science.gov (United States)

    Bardgett, Megan E.; Chen, Qing-Hui; Guo, Qing; Calderon, Alfredo S.; Andrade, Mary Ann

    2014-01-01

    Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-d-aspartate (NMDA) receptors reduced (P dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases. PMID:24671240

  11. Cardiorenal axis and arrhythmias: Will renal sympathetic denervation provide additive value to the therapeutic arsenal?

    NARCIS (Netherlands)

    van Brussel, Peter M.; Lieve, Krystien V. V.; de Winter, Robbert J.; Wilde, Arthur A. M.

    2015-01-01

    Disruption of sympathetic tone may result in the occurrence or maintenance of cardiac arrhythmias. Multiple arrhythmic therapies that intervene by influencing cardiac sympathetic tone are common in clinical practice. These vary from pharmaceutical (β-blockers, angiotensin-converting enzyme

  12. Baroreflex control of muscle sympathetic nerve activity after carotid body tumor resection

    NARCIS (Netherlands)

    Timmers, Henri J. L. M.; Karemaker, John M.; Wieling, Wouter; Marres, Henri A. M.; Lenders, Jacques W. M.

    2003-01-01

    Bilateral carotid body tumor resection causes a permanent attenuation of vagal baroreflex sensitivity. We retrospectively examined the effects of bilateral carotid body tumor resection on the baroreflex control of sympathetic nerve traffic. Muscle sympathetic nerve activity was recorded in 5

  13. Suppressed sympathetic outflow to skeletal muscle, muscle thermogenesis, and activity energy expenditure with calorie restriction.

    Science.gov (United States)

    Almundarij, Tariq I; Gavini, Chaitanya K; Novak, Colleen M

    2017-02-01

    During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity-associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account. Along with a decreased caloric need for low-to-moderate-intensity treadmill activity with 50% CR, baseline and activity-related muscle thermogenesis were also suppressed, though the ability to increase muscle thermogenesis above baseline levels was not compromised. When sympathetic drive was measured by assessing norepinephrine turnover (NETO), 50% CR was found to decrease NETO in three of the four muscle groups examined, whereas elevated NETO was found in white adipose tissue of food-restricted rats. Central activation of melanocortin 4 receptors in the ventromedial hypothalamus stimulated this pathway, enhancing activity EE; this was not compromised by 50% CR These data suggest that suppressed activity EE contributes to adaptive thermogenesis during energy restriction. This may stem from decreased sympathetic drive to skeletal muscle, increasing locomotor efficiency and reducing skeletal muscle thermogenesis. The capacity to increase activity EE in response to central stimuli is retained, however, presenting a potential target for preventing weight regain. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  14. Understanding how pain education causes changes in pain and disability: protocol for a causal mediation analysis of the PREVENT trial

    Directory of Open Access Journals (Sweden)

    Hopin Lee

    2015-07-01

    Discussion and significance: Mediation analysis of clinical trials can estimate how much the total effect of the treatment on the outcome is carried through an indirect path. Using mediation analysis to understand these mechanisms can generate evidence that can be used to tailor treatments and optimise treatment effects. In this study, the causal mediation effects of a pain education intervention for acute non-specific low back pain will be estimated. This knowledge is critical for further development and refinement of interventions for conditions such as low back pain.

  15. The clinical value of cardiac sympathetic imaging in heart failure

    DEFF Research Database (Denmark)

    Christensen, Thomas Emil; Kjaer, Andreas; Hasbak, Philip

    2014-01-01

    The autonomic nervous system plays an important role in the pathology of heart failure. The single-photon emission computed tomography tracer iodine-123-metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of the predominant neurotransmitter of the sympathetic nervous...

  16. Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms

    Directory of Open Access Journals (Sweden)

    Jasdeep Kaur

    2017-08-01

    Full Text Available The incidence of chronic kidney disease (CKD is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.

  17. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  18. Sympathetic neural responses to smoking are age dependent

    Czech Academy of Sciences Publication Activity Database

    Hering, D.; Somers, V. K.; Kára, T.; Kucharska, W.; Jurák, Pavel; Bieniaszewski, L.; Narkiewicz, K.

    2006-01-01

    Roč. 24, č. 4 (2006), s. 691-695 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA102/05/0402 Institutional research plan: CEZ:AV0Z20650511 Keywords : sympathetic neural response * blood pressure * heart rate * smoking Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 4.021, year: 2006

  19. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA

    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  20. Modulation of sympathetic outflow by centrally acting antihypertensive drugs

    NARCIS (Netherlands)

    van Zwieten, P. A.

    1996-01-01

    The modulation of peripheral sympathetic activity by the central nervous system (CNS) has been intensely investigated as a potential target of antihypertensive drugs. In particular, clonidine, guanfacine, and alpha-methyl-DOPA (acting via its metabolite alpha-methylnoradrenaline) have been developed

  1. Axillary Brachial Plexus Blockade for the Reflex Sympathetic Dystrophy Syndrome.

    Science.gov (United States)

    Ribbers, G. M.; Geurts, A. C. H.; Rijken, R. A. J.; Kerkkamp, H. E. M.

    1997-01-01

    Reflex sympathetic dystrophy syndrome (RSD) is a neurogenic pain syndrome characterized by pain, vasomotor and dystrophic changes, and often motor impairments. This study evaluated the effectiveness of brachial plexus blockade with local anaesthetic drugs as a treatment for this condition. Three patients responded well; three did not. (DB)

  2. Juxta-articular erosions in reflex sympathetic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, H.J.; Virtama, P.

    Thirty-one patients with documented reflex sympathetic dystrophy syndrome (RSDS) were reviewed for their radiographic changes. Juxta-articular and metaphyseal bone loss was found in the majority of the patients. Juxta-articular bone loss closely resembling erosions seen in rheumatoid arthritis was found in all the patients. The significance of these findings is discussed.

  3. Reflex sympathetic dystrophy/complex regional pain syndrome.

    Science.gov (United States)

    Gann, Charlotte

    2008-02-01

    Occupational health nurses are usually the first to assess workers with reflex sympathetic dystrophy/complex regional pain syndrome. Therefore, they must be aware of the signs and symptoms, implications for lost time, and higher incidence of disability related to this disorder.

  4. Reflex sympathetic dystrophy syndrome due to arteriovenous fistula.

    Science.gov (United States)

    Unek, Ilkay Tugba; Birlik, Merih; Cavdar, Caner; Ersoy, Rifki; Onen, Fatos; Celik, Ali; Camsari, Taner

    2005-10-01

    A patient with end-stage renal disease presented with reflex sympathetic dystrophy syndrome (RSDS) on her left hand 1 month after arteriovenous fistula (AVF) surgery. Magnetic resonance angiography revealed steal syndrome at the AVF level. Bone scintigraphy revealed early-stage RSDS. We considered that arterial insufficiency because of steal phenomenon following AVF surgery and underlying occlusive arterial disease triggered RSDS development.

  5. Complex regional pain syndrome/reflex sympathetic dystrophy.

    Science.gov (United States)

    Jakubowicz, Brian; Aner, Musa

    2010-06-01

    Questions from patients about analgesic pharmacotherapy and responses from the authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are the signs, symptoms, and diagnosis of complex regional pain syndrome/reflex sympathetic dystrophy.

  6. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    International Nuclear Information System (INIS)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

    2015-01-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  7. Reflex sympathetic dystrophy/complex regional pain syndrome, type 1

    African Journals Online (AJOL)

    Enrique

    over the left ankle was also present. (Fig. 6 and Figs 7a and 7b). There was contradiction between the two diagnoses of stress fractures and CPRS type 1. As CPRS type 1 is a clinical diagnosis the boy was treated as such. He was admitted into hospital and received epidural narcotic infusion with sympathetic blockage for a ...

  8. Baroreflex control of sympathetic activity in experimental hypertension

    Directory of Open Access Journals (Sweden)

    M.C.C. Irigoyen

    1998-09-01

    Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

  9. Prolonged Paroxysmal Sympathetic Storming Associated with Spontaneous Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2013-01-01

    Full Text Available Paroxysmal sympathetic storming (PSS is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH, there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.

  10. RESTING SYMPATHETIC BAROREFLEX SENSITIVITY IN SUBJECTS WITH LOW AND HIGH TOLERANCE TO CENTRAL HYPOVOLEMIA INDUCED BY LOWER BODY NEGATIVE PRESSURE

    Directory of Open Access Journals (Sweden)

    Carmen eHinojosa-Laborde

    2014-06-01

    Full Text Available Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock. The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA and sympathetic baroreflex sensitivity (BRS are attenuated in male and female subjects who have low tolerance (LT to central hypovolemia induced by lower body negative pressure (LBNP. MSNA and diastolic arterial pressure (DAP were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms. LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28, and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats-1•mmHg-1, p=0.29. We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS.

  11. Neural and sympathetic activity associated with exploration in decision-making: Further evidence for involvement of insula

    Directory of Open Access Journals (Sweden)

    Hideki eOhira

    2014-11-01

    Full Text Available We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition and a condition with high uncertainty of gain/loss (random-reward condition. Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET, and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.

  12. Pretreatment of Sialic Acid Efficiently Prevents Lipopolysaccharide-Induced Acute Renal Failure and Suppresses TLR4/gp91-Mediated Apoptotic Signaling

    Directory of Open Access Journals (Sweden)

    Shih-Ping Hsu

    2016-05-01

    Full Text Available Background/Aims: Lipopolysaccharides (LPS binding to Toll-like receptor 4 (TLR4 activate NADPH oxidase gp91 subunit-mediated inflammation and oxidative damage. Recognizing the high binding affinity of sialic acid (SA with LPS, we further explored the preventive potential of SA pretreatment on LPS-evoked acute renal failure (ARF. Methods: We determined the effect of intravenous SA 30 min before LPS-induced injury in urethane-anesthetized female Wistar rats by evaluating kidney reactive oxygen species (ROS responses, renal and systemic hemodynamics, renal function, histopathology, and molecular mechanisms. Results: LPS time-dependently reduced arterial blood pressure, renal microcirculation, and increased blood urea nitrogen and creatinine in the rats. LPS enhanced monocyte/macrophage infiltration and ROS production, and subsequently impaired kidneys with the enhancement of TLR4/NADPH oxidase gp91/Caspase 3/poly-(ADP-ribose-polymerase (PARP-mediated apoptosis in the kidneys. SA pretreatment effectively alleviated LPS-induced ARF. The levels of LPS-increased ED-1 infiltration and ROS production in the kidney were significantly depressed by SA pretreatment. Furthermore, SA pretreatment significantly depressed TLR4 activation, gp91 expression, and Caspase 3/PARP induced apoptosis in the kidneys. Conclusion: We suggest that pretreatment of SA significantly and preventively attenuated LPS-induced detrimental effects on systemic and renal hemodynamics, renal ROS production and renal function, as well as, LPS-activated TLR4/gp91/Caspase3 mediated apoptosis signaling.

  13. Relationship between three phase bone scintigram and prognosis after sympathetic blockade in reflex sympathetic dystrophy of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Yokono, Atsuko; Yokono, Satoshi; Oguri, Kenji (Kagawa Medical School, Miki (Japan))

    1990-11-01

    The authors attempted to correlate the changes in three phase bone scintigram (TPBS) with prognosis after sympathetic blockade in reflex sympathetic dystrophy (RSD) of the hand. Subjects were 12 patients of RSD in acute or dystrophic stage, who all had increased images on TPBS. Either intravenous regional sympathectomy with guanethidine or stellate ganglion block was performed repeatedly. We compared TPBS obtained just before and after this series of sympathetic blocks and evaluated the eventual recovery of function of the hand. In 8 patients, blood flow (phase 1) image of TPBS decreased after the blockade. Of these patients, those who showed almost normalized tracer activity not only on flow image but on blood pool (phase 2) and delayed (phase 3) image, returned to normal. But others with normalized blood flow and still increased activity in blood pool and delayed image, remained with mild contracture of the hand. These results suggest that normalization of blood pool and delayed image on TPBS is a predictor of subsequent recovery after sympathetic blockade in RSD. (author).

  14. Continuous Thoracic Sympathetic Ganglion Block in Complex Regional Pain Syndrome Patients with Spinal Cord Stimulation Implantation

    Directory of Open Access Journals (Sweden)

    EungDon Kim

    2016-01-01

    Full Text Available The sympathetic block is widely used for treating neuropathic pain such as complex regional pain syndrome (CRPS. However, single sympathetic block often provides only short-term effect. Moreover, frequent procedures for sympathetic block may increase the risk of complications. The use of epidural route may be limited by concern of infection in case of previous implantation of the spinal cord stimulation (SCS. In contrast, a continuous sympathetic block can be administered without such concerns. The continuous thoracic sympathetic block (TSGB has been used to treat the ischemic disease and other neuropathic conditions such as postherpetic neuralgia. We administered continuous thoracic sympathetic block using catheter in CRPS patients who underwent SCS implantations and achieved desirable outcomes. We believe a continuous sympathetic block is a considerable option before performing neurolysis or radiofrequency rhizotomy and even after SCS implantation.

  15. Effects of a combined parent-student alcohol prevention program on intermediate factors and adolescents' drinking behavior: A sequential mediation model.

    Science.gov (United States)

    Koning, Ina M; Maric, Marija; MacKinnon, David; Vollebergh, Wilma A M

    2015-08-01

    Previous work revealed that the combined parent-student alcohol prevention program (PAS) effectively postponed alcohol initiation through its hypothesized intermediate factors: increase in strict parental rule setting and adolescents' self-control (Koning, van den Eijnden, Verdurmen, Engels, & Vollebergh, 2011). This study examines whether the parental strictness precedes an increase in adolescents' self-control by testing a sequential mediation model. A cluster randomized trial including 3,245 Dutch early adolescents (M age = 12.68, SD = 0.50) and their parents randomized over 4 conditions: (1) parent intervention, (2) student intervention, (3) combined intervention, and (4) control group. Outcome measure was amount of weekly drinking measured at age 12 to 15; baseline assessment (T0) and 3 follow-up assessments (T1-T3). Main effects of the combined and parent intervention on weekly drinking at T3 were found. The effect of the combined intervention on weekly drinking (T3) was mediated via an increase in strict rule setting (T1) and adolescents' subsequent self-control (T2). In addition, the indirect effect of the combined intervention via rule setting (T1) was significant. No reciprocal sequential mediation (self-control at T1 prior to rules at T2) was found. The current study is 1 of the few studies reporting sequential mediation effects of youth intervention outcomes. It underscores the need of involving parents in youth alcohol prevention programs, and the need to target both parents and adolescents, so that change in parents' behavior enables change in their offspring. (c) 2015 APA, all rights reserved).

  16. Two Distinct Mediated Pathways to Disordered Eating in Response to Weight Stigmatization and Their Application to Prevention Programs

    Science.gov (United States)

    Simone, Melissa; Lockhart, Ginger

    2016-01-01

    Objective: Disordered eating behaviors among undergraduate women are common and, thus, are an important public health concern. Weight stigmatization, stress, and social withdrawal are often associated with disordered eating behaviors; however, it is unclear whether stress and social withdrawal act as mediators between weight stigmatization and…

  17. Simulating sympathetic detonation using the hydrodynamic models and constitutive equations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo Hoon; Kim, Min Sung; Yoh, Jack J. [Dept. of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea, Republic of); Sun, Tae Boo [Hanwha Corporation Defense Rand D Center, Daejeon (Korea, Republic of)

    2016-12-15

    A Sympathetic detonation (SD) is a detonation of an explosive charge by a nearby explosion. Most of times it is unintended while the impact of blast fragments or strong shock waves from the initiating donor explosive is the cause of SD. We investigate the SD of a cylindrical explosive charge (64 % RDX, 20 % Al, 16 % HTPB) contained in a steel casing. The constitutive relations for high explosive are obtained from a thermo-chemical code that provides the size effect data without the rate stick data typically used for building the rate law and equation of state. A full size SD test of eight pallet-packaged artillery shells is performed that provides the pressure data while the hydrodynamic model with proper constitutive relations for reactive materials and the fragmentation model for steel casing is conducted to replicate the experimental findings. The work presents a novel effort to accurately model and reproduce the sympathetic detonation event with a reduced experimental effort.

  18. Simulating sympathetic detonation using the hydrodynamic models and constitutive equations

    International Nuclear Information System (INIS)

    Kim, Bo Hoon; Kim, Min Sung; Yoh, Jack J.; Sun, Tae Boo

    2016-01-01

    A Sympathetic detonation (SD) is a detonation of an explosive charge by a nearby explosion. Most of times it is unintended while the impact of blast fragments or strong shock waves from the initiating donor explosive is the cause of SD. We investigate the SD of a cylindrical explosive charge (64 % RDX, 20 % Al, 16 % HTPB) contained in a steel casing. The constitutive relations for high explosive are obtained from a thermo-chemical code that provides the size effect data without the rate stick data typically used for building the rate law and equation of state. A full size SD test of eight pallet-packaged artillery shells is performed that provides the pressure data while the hydrodynamic model with proper constitutive relations for reactive materials and the fragmentation model for steel casing is conducted to replicate the experimental findings. The work presents a novel effort to accurately model and reproduce the sympathetic detonation event with a reduced experimental effort

  19. Regulation of the renal sympathetic nerves in heart failure

    Directory of Open Access Journals (Sweden)

    Rohit eRamchandra

    2015-08-01

    Full Text Available Heart failure (HF is a serious debilitating condition with poor survival rates and an increasing level of prevalence. Heart failure is associated with an increase in renal norepinephrine spillover, which is an independent predictor of mortality in HF patients. The excessive sympatho-excitation that is a hallmark of heart failure has long-term effects that contribute to disease progression. An increase in directly recorded renal sympathetic nerve activity has also been recorded in animal models of heart failure. This review will focus on the mechanisms controlling sympathetic nerve activity to the kidney during normal conditions and alterations in these mechanisms during heart failure. In particular the roles of afferent reflexes and central mechanisms will be discussed.

  20. The biophysics of renal sympathetic denervation using radiofrequency energy.

    Science.gov (United States)

    Patel, Hitesh C; Dhillon, Paramdeep S; Mahfoud, Felix; Lindsay, Alistair C; Hayward, Carl; Ernst, Sabine; Lyon, Alexander R; Rosen, Stuart D; di Mario, Carlo

    2014-05-01

    Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

  1. Sympathetic skin response in acute sensory ataxic neuropathy.

    Science.gov (United States)

    Arunodaya, G R; Taly, A B; Swamy, H S

    1995-05-01

    Sympathetic skin response (SSR) is a recently described objective method of studying sudomotor sympathetic nerve function and has been studied in a variety of peripheral neuropathies. We report SSR changes in nine patients with acute sensory ataxic neuropathy (ASAN). All had severe sensory and mild motor nerve conduction abnormalities; five had dysautonomia. SSR, elicited by electric shock and cough stimuli, was absent in three patients. Latency was normal in all when SSR was present. Two patients had SSR amplitude of 0.2 mV or less. Absence of SSR did not correlate with dysautonomia, absence of sensory nerve action potential or motor nerve conduction abnormalities. Follow up SSR studies revealed return of absent SSR in one patient over a period of 3 months, despite persistence of ataxia. To our knowledge, this is the first report of SSR changes in ASAN.

  2. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    OpenAIRE

    Tsioufis, Costas; Kordalis, Athanasios; Flessas, Dimitris; Anastasopoulos, Ioannis; Tsiachris, Dimitris; Papademetriou, Vasilios; Stefanadis, Christodoulos

    2011-01-01

    Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge po...

  3. A Rare Tumor in the Cervical Sympathetic Trunk: Ganglioneuroblastoma

    Directory of Open Access Journals (Sweden)

    Ozan Erol

    2016-01-01

    Full Text Available Ganglioneuroblastoma is a rare tumor with moderate malignancy, which is composed of mature ganglion cells and seen in sympathetic ganglia and adrenal medulla. The diagnosis is possible after cytological and immunohistochemical studies following a needle biopsy or surgical excision. There is no consensus regarding the need for chemo- or radiotherapy after surgery. In this case report, clinical behavior and diagnosis and treatment of the rare tumor cervical ganglioneuroblastoma were discussed.

  4. Unilateral trachyonychia in a patient with reflex sympathetic dystrophy.

    Science.gov (United States)

    Pucevich, Brian; Spencer, Lori; English, Joseph C

    2008-02-01

    Reflex sympathetic dystrophy (RSD) is a poorly understood neurovascular disorder characterized by pain, altered sensation, motor disturbance, soft tissue changes, vasomotor changes, and autonomic changes that occurs after trauma to an extremity. Unilateral leukonychia, Beau's lines, nailfold swelling, and nail clubbing have been an observed sequela of RSD. We present a case of a unilateral atypical trachyonychia occurring in the setting of RSD after traumatic fracture of a digit.

  5. Reflex sympathetic dystrophy in the hands: clinical and scintigraphic criteria

    Energy Technology Data Exchange (ETDEWEB)

    Holder, L.E.; Mackinnon, S.E.

    1984-08-01

    In an attempt to establish specific scintigraphic criteria for the reflex sympathetic dystrophy syndrome (RSD) as defined by a group of specialized hand surgeons, 145 consecutive patients, 23 of whom had clinical RSD, underwent three phase radionuclide bone scanning (TPBS). Specific patterns for positive radionuclide angiogram, blood pool, and delayed images were established. The delayed images were sensitive (96%), specific (97%), and had a valuable negative predictive value (99%). It was concluded that TPBS could provide an objective marker for RSD.

  6. [Hemopneumothorax after thoracic sympathetic nerve block; report of a case].

    Science.gov (United States)

    Sakai, Takehiro; Sano, Atsushi; Matsukura, Akira; Kikuchi, Junko; Taguchi, Taizo; Tanizaki, Yuji; Hamashima, Hideki; Kimura, Daisuke; Hatanaka, Ryo; Yamada, Yoshitsugu; Tsushima, Takao; Fukuda, Ikuo

    2014-07-01

    A 72-year-old man, who had been treated pneumothorax 50 years ago, visited a physician complaining of dyspnea after thoracic sympathetic nerve block for postherpetic neuralgia. The patient was diagnosed as pneumothorax, and was consulted to our hospital. Clinical sign and the chest radiography suggested tension hemopneumothorax, and the chest drainage was immediately performed. Although bloody fluid of 1,100 ml was initially drained, no further increase was noted. The patient was discharged on the 21st hospital day.

  7. Responses of muscle spindles in feline dorsal neck muscles to electrical stimulation of the cervical sympathetic nerve.

    Science.gov (United States)

    Hellström, F; Roatta, S; Thunberg, J; Passatore, M; Djupsjöbacka, M

    2005-09-01

    , changes in sympathetic outflow can modulate the afferent signals from muscle spindles through an action exerted directly on the spindles, independent of changes in blood flow. It is suggested that such an action may be one of the mechanisms mediating the onset of chronic muscle pain in these muscles in humans.

  8. Sympathetic cooling of ions in a hybrid atom ion trap

    Energy Technology Data Exchange (ETDEWEB)

    Hoeltkemeier, Bastian

    2016-10-27

    In this thesis the dynamics of a trapped ion immersed in a spatially localized buffer gas is investigated. For a homogeneous buffer gas, the ion's energy distribution reaches a stable equilibrium only if the mass of the buffer gas atoms is below a critical value. This limitation can be overcome by using multipole traps in combination and/or a spatially confined buffer gas. Using a generalized model for elastic collisions of the ion with the buffer gas atoms, the ion's energy distribution is numerically determined for arbitrary buffer gas distributions and trap parameters. Three regimes characterized by the respective analytic form of the ion's equilibrium energy distribution are found. One of these is a novel regime at large atom-to-ion mass ratios where the final ion temperature can tuned by adiabatically decreasing the spatial extension of the buffer gas and the effective ion trap depth (forced sympathetic cooling). The second part of the thesis presents a hybrid atom ion trap designed for sympathetic cooling of hydroxide anions. In this hybrid trap the anions are immersed in a cloud of laser cooled rubidium atoms. The translational and rovibrational temperatures of the anions is probed by photodetachment tomography and spectroscopy which shows the first ever indication of sympathetic cooling of anions by laser cooled atoms.

  9. Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II

    Directory of Open Access Journals (Sweden)

    Noureddine Idris-Khodja

    2013-01-01

    Full Text Available This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO and endothelium-derived hyperpolarization (EDH in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs, a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa and connexin 40 (Cx40, which are involved in EDH-type relaxations, endothelial NO synthase (eNOS, angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.

  10. Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.

    LENUS (Irish Health Repository)

    Barry, Andrew E

    2011-05-18

    Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-containing aqueous extracts of Alzheimer\\'s disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.

  11. Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis.

    Science.gov (United States)

    Klenner, Lars; Hafezi, Wali; Clausen, Björn E; Lorentzen, Eva U; Luger, Thomas A; Beissert, Stefan; Kühn, Joachim E; Loser, Karin

    2015-11-01

    Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system, and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to come into contact with the virus, it has been shown that the processing of viral antigens and the differentiation of antiviral CTLs are mediated by migratory CD103(+) dermal DCs and CD8α(+) lymph node-resident DCs. In vivo regulatory T-cells (Tregs) are implicated in the regulation of antiviral immunity and we have shown that signaling via the receptor activator of NF-κB (RANK) and its ligand RANKL mediates the peripheral expansion of Tregs. However, in addition to expanding Tregs, RANK-RANKL interactions are involved in the control of antimicrobial immunity by upregulating the priming of CD4(+) effector T cells in LCMV infection or by the generation of parasite-specific CD8(+) T cells in Trypanosoma cruzi infection. Here, we demonstrate that cutaneous RANK-RANKL signaling is critical for the induction of CD8-mediated antiviral immune responses during HSV-1 infection of the skin by preventing virus-induced LC apoptosis, improving antigen transport to regional lymph nodes, and increasing the CTL priming capacity of lymph node DCs.

  12. Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

    Science.gov (United States)

    Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

    2014-12-01

    Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

  13. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1

    DEFF Research Database (Denmark)

    Bai, Bo; Man, Andy W C; Yang, Kangmin

    2016-01-01

    Aims-SIRT1 exerts potent activity against cellular senescence and vascular ageing. By decreasing LKB1 protein levels, it promotes the survival and regeneration of endothelial cells. The present study aims to investigate the molecular mechanisms underlying SIRT1-mediated LKB1 degradation......-directed mutagenesis revealed that acetylation at lysine (K) 64 of LKB1 triggers the formation of SIRT1/HERC2/LKB1 protein complex and subsequent proteasomal degradation. In vitro cellular studies suggested that accumulation of acetylated LKB1 in the nucleus leads to endothelial activation, in turn stimulating...

  14. Baroreflex control of muscle sympathetic nerve activity: a nonpharmacological measure of baroreflex sensitivity

    OpenAIRE

    Hart, Emma C.; Joyner, Michael J.; Wallin, B. Gunnar; Karlsson, Tomas; Curry, Timothy B.; Charkoudian, Nisha

    2009-01-01

    The sensitivity of baroreflex control of sympathetic nerve activity (SNA) represents the responsiveness of SNA to changes in blood pressure. In a slightly different analysis, the baroreflex threshold measures the probability of whether a sympathetic burst will occur at a given diastolic blood pressure. We hypothesized that baroreflex threshold analysis could be used to estimate the sensitivity of the sympathetic baroreflex measured by the pharmacological modified Oxford test. We compared four...

  15. Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies

    DEFF Research Database (Denmark)

    Henriksen, J H; Ring-Larsen, H; Christensen, N J

    1985-01-01

    This review summarizes recent progress in the knowledge of catecholamines in cirrhosis. Compensated patients have normal plasma concentration of noradrenaline. Highly elevated plasma noradrenaline concentration in decompensated patients indicates that the sympathetic nervous system is enhanced...... in this condition. This may especially apply to the sympathetic tone in the kidney, as evaluated by regional measurements of noradrenaline overflow. Hepatic elimination of catecholamines is only slightly reduced. Activation of the sympathetic nervous system seems to play an important role in the avid sodium...

  16. Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

    Science.gov (United States)

    Iliescu, Radu

    2012-01-01

    Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

  17. Burst Activity and Heart Rhythm Modulation in the Sympathetic Outflow to the Heart

    National Research Council Canada - National Science Library

    Baselli, G

    2001-01-01

    In 13 decerebrate, artificially ventilated cats preganglionic sympathetic outflow to the heart was recorded with ECG and ventilation signal, A novel algorithm was implemented that extracts weighted...

  18. Marital conflict and children's externalizing behavior: interactions between parasympathetic and sympathetic nervous system activity

    National Research Council Canada - National Science Library

    El-Sheikh, Mona; Beauchaine, Theodore P; Moore, Ginger A

    2009-01-01

    "Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS...

  19. Liquiritigenin prevents Staphylococcus aureus-mediated lung cell injury via inhibiting the production of α-hemolysin.

    Science.gov (United States)

    Dai, Xiao-Han; Li, Hong-En; Lu, Chong-Jian; Wang, Jiang-Feng; Dong, Jing; Wei, Jing-Yuan; Zhang, Yu; Wang, Xin; Tan, Wei; Deng, Xu-Ming; Zhao, Shu-Hua; Zhang, Ming-Jun

    2013-01-01

    Staphylococcus aureus is a significant Gram-positive bacterium that is associated with a broad spectrum of diseases ranging from minor skin infections to lethal pneumonia, endocarditis, and toxinoses. α-Hemolysin is one of the most important exotoxins that contribute to the pathogenesis of S. aureus infections. Liquiritigenin is one of the most significant active components in licorice. In this study, hemolysis, western blot, and real-time reverse transcription-PCR assays were performed to investigate the impact of liquiritigenin on the production of S. aureus α-hemolysin. The results showed that low concentrations of liquiritigenin remarkably decreased S. aureus α-hemolysin production in a dose-dependent manner. Using live/dead cell staining and lactate dehydrogenase assays, we found that liquiritigenin could protect human lung cells (A549) from α-hemolysin-mediated injury. The data indicated that this compound could potentially be useful in developing drugs aiming at staphylococcal α-hemolysin.

  20. Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation.

    Science.gov (United States)

    Weng, Yueh-Shan; Wang, Hsueh-Fang; Pai, Pei-Ying; Jong, Gwo-Ping; Lai, Chao-Hung; Chung, Li-Chin; Hsieh, Dennis Jine-Yuan; HsuanDay, Cecilia; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-01-01

    IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17[Formula: see text]-estradiol (E[Formula: see text]. However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.

  1. Intermedin in the paraventricular nucleus attenuates cardiac sympathetic afferent reflex in chronic heart failure rats.

    Directory of Open Access Journals (Sweden)

    Xian-Bing Gan

    Full Text Available BACKGROUND AND AIM: Intermedin (IMD is a member of calcitonin/calcitonin gene-related peptide (CGRP family together with adrenomedullin (AM and amylin. It has a wide distribution in the central nervous system (CNS especially in hypothalamic paraventricular nucleus (PVN. Cardiac sympathetic afferent reflex (CSAR is enhanced in chronic heart failure (CHF rats. The aim of this study is to determine the effect of IMD in the PVN on CSAR and its related mechanisms in CHF rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to left descending coronary artery ligation to induce CHF or sham-operation (Sham. Renal sympathetic nerve activity (RSNA, mean arterial pressure (MAP and heart rate (HR were recorded. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Acute experiments were carried out 8 weeks after coronary ligation or sham surgery under anesthesia. IMD and angiotensin II (Ang II levels in the PVN were up-regulated in CHF rats. Bilateral PVN microinjection of IMD caused greater decreases in CSAR and the baseline RSNA and MAP in CHF rats than those in Sham rats. The decrease of CSAR caused by IMD was prevented by pretreatment with AM receptor antagonist AM22-52, but not CGRP receptor antagonist CGRP8-37. Ang II in the PVN significantly enhanced CSAR and superoxide anions level, which was inhibited by PVN pretreatment with IMD or tempol (a superoxide anions scavenger in Sham and CHF rats. CONCLUSION: IMD in the PVN inhibits CSAR via AM receptor, and attenuates the effects of Ang II on CSAR and superoxide anions level in CHF rats. PVN superoxide anions involve in the effect of IMD on attenuating Ang II-induced CSAR response.

  2. Sympathetic activity during passive heat stress in healthy aged humans.

    Science.gov (United States)

    Gagnon, Daniel; Schlader, Zachary J; Crandall, Craig G

    2015-05-01

    Cardiovascular adjustments to heat stress are attenuated in healthy aged individuals, which could contribute to their greater prevalence of heat-related illnesses and deaths during heat waves. The attenuated cardiovascular adjustments in the aged could be due to lower increases in sympathetic nerve activity during heat stress. We examined muscle sympathetic nerve activity (MSNA) and plasma catecholamine concentrations in healthy young and aged individuals during whole-body passive heat stress. The main finding of this study is that increases in MSNA and plasma catecholamine concentrations did not differ between young and aged healthy individuals during passive heating. Furthermore, the increase in these variables did not differ when a cold pressor test and lower body negative pressure were superimposed upon heating. These findings suggest that attenuated cardiovascular adjustments to heat stress in healthy aged individuals are unlikely to be related to attenuated increases in sympathetic activity. Cardiovascular adjustments during heat stress are generally attenuated in healthy aged humans, which could be due to lower increases in sympathetic activity compared to the young. We compared muscle sympathetic nerve activity (MSNA) between 11 young (Y: 28 ± 4 years) and 10 aged (A: 70 ± 5 years) subjects prior to and during passive heating. Furthermore, MSNA responses were compared when a cold pressor test (CPT) and lower body negative pressure (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 ± 4 vs. A: 31 ± 3 bursts min(-1) , P ≤ 0.01) and burst incidence (Y: 26 ± 8 vs. A: 50 ± 7 bursts (100 cardiac cycles (CC))(-1) , P ≤ 0.01) were greater in the aged. Heat stress increased core temperature to a similar extent in both groups (Y: +1.2 ± 0.1 vs. A: +1.2 ± 0.0°C, P = 0.99). Absolute levels of MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 ± 6 vs. A: 63 ± 11

  3. Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Theofilos Tourtas

    Full Text Available Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H₂O₂, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H₂O₂ further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H₂O₂ stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H₂O₂ mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H₂O₂ induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side

  4. Explosives malfunction from sympathetic detonation to shock desensitization

    Energy Technology Data Exchange (ETDEWEB)

    Katsabanis, P.D.; Yeung, C.; Fitz, G.; Heater, R. [Queen`s Univ., Kingston, Ontario (Canada). Dept. of Mining Engineering

    1994-12-31

    Explosives malfunction due to shock waves is a serious concern for successful blasting results. Malfunction can range from sympathetic detonation to desensitization and modification of firing times of conventional pyrotechnic detonators. Decked charges consisting of commercial emulsion explosives having a detonator and a primer were placed in 10cm diameter blastholes and their performance was recorded. Due to the limited length of the holes the events were mainly sympathetic detonations although desensitization was also recorded. Pressure measurements along the stemming column showed that shock waves produced by an explosive have a significant amplitude even at relatively large distances away from the detonating explosive. It was found that 2m away from a detonating charge the pressures in the stemming material were above 0.1 GPa indicating that there is potential for primers and detonators to malfunction. Parallel charges consisting of a commercial emulsion explosive with a diameter of 32mm were confined in 2mm thick steel tubes and initiation was attempted using detonators having a delay interval of 25ms. The charges were placed in sand and the velocity of detonation of the acceptor charge was recorded using a continuous resistance probe system. Carbon resistors were also placed in the same position as the acceptor charge to examine the dynamic pressures that were applied to the charge. Sympathetic detonation, complete desensitization, partial desensitization and properly sequenced detonations were observed as the distance between charges was increased from 76 mm to 305 mm. Delay detonators were also tested in a similar to the last configuration. Modification of firing times was observed at distances between 150 and 360 mm.

  5. TARGETED STELLATE DECENTRALIZATION: IMPLICATIONS FOR SYMPATHETIC CONTROL OF VENTRICULAR ELECTROPHYSIOLOGY

    Science.gov (United States)

    Buckley, Una; Yamakawa, Kentaro; Takamiya, Tatsuo; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

    2015-01-01

    Background Selective, bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. The procedure currently employed removes the caudal portions of both stellate ganglia, along with thoracic chain ganglia down to T4 ganglia. Objective To define the relative contributions of T1-T2 and the T3-T4 paravertebral ganglia in modulating ventricular electrical function. Methods In anesthetized vagotomised porcine subjects (n=8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation recovery intervals (ARI) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated following surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. Results In intact preparations, stellate ganglion vs T3 stimuli (4Hz, 4ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right-side 85±6 vs 55±10 ms; left-side 24±3 vs 17±7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate-T2 ganglion removal. Following acute decentralization, T3 stimulation failed to change ARIs. Conclusion Preganglionic sympathetic efferents arising from the T1-T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. T1-T2 surgical excision is thus sufficient to functionally interrupt central control of peripheral sympathetic efferent activity. PMID:26282244

  6. Sympathetic stimulation alters left ventricular relaxation and chamber size.

    Science.gov (United States)

    Burwash, I G; Morgan, D E; Koilpillai, C J; Blackmore, G L; Johnstone, D E; Armour, J A

    1993-01-01

    Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.

  7. Study of sympathetic nerve activity in young Indian obese individuals

    Directory of Open Access Journals (Sweden)

    B Kalpana

    2013-01-01

    Full Text Available Background: Obesity is the culmination of a chronic imbalance between energy intake and energy expenditure. This energy balance can be potentially affected by the activity of autonomic nervous system (ANS. Altered sympathetic nerve function may be of importance in obesity. Objective: The present study is an attempt to pinpoint the defect (if any in the activity of sympathetic limb of the ANS in obesity, by subjecting to isometric exercise stress. Materials and Methods: A total of 81 females belonging to the age group of 18-22 years were recruited for the study. The participants were divided into two groups as normal weight and obese based on WHO guidelines for Asia Pacific region. After recording the resting blood pressure, they were subjected to isometric exercise by Handgrip dynamometer. Blood pressure was recorded again, and the difference was noted down. All recorded parameters were compared between two groups using unpaired t test. The relationship between body mass index (BMI and rise in diastolic pressure was quantified by Pearson′s correlation test. A P value less than 0.05 was considered as significant. Results: In obese, the diastolic pressure was significantly higher at rest, but showed reduced rise during handgrip test in comparison with normal weight individuals. Also, the rise in diastolic pressure exhibited a negative relation with BMI. Conclusion: The result is suggestive of impaired autonomic function at rest and reduced sympathetic activity in the group of obese when subjected to stress. This could make them more prone for future development of hypertension or other cardiovascular disorders.

  8. The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition.

    Science.gov (United States)

    Casilag, Fiordiligie; Lorenz, Anne; Krueger, Jonas; Klawonn, Frank; Weiss, Siegfried; Häussler, Susanne

    2016-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of P. aeruginosa PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for P. aeruginosa to ensure the maintenance of protease-dependent immune-modulating functions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, J., E-mail: jens.ricke@med.ovgu.de; Seidensticker, M.; Becker, S. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Schiefer, J. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany); Adamchic, I.; Lohfink, K. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Kandulski, M.; Heller, A.; Mertens, P. R. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany)

    2016-02-15

    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

  10. MK-82 bomb characterization for the sympathetic detonation study

    Energy Technology Data Exchange (ETDEWEB)

    Lucht, R.A.; Hantel, L.W.

    1988-01-01

    Optical, radiographic, and electronic pin techniques were used to evaluate the fragmentation of tail- and side-initiated MK-82 MOD 1 general purpose bombs. They were found to contain large voids, randomly located from bomb to bomb, in the Tritonal explosive fill. Characteristics of the void-side performance of the bomb were found to be as much as 10% different from the nonvoid side and were much less reproducible than the characteristics of the nonvoid side. The data collected will be useful in evaluating sympathetic detonation mitigation systems designed for use with the bombs. 12 figs., 3 tabs.

  11. Bone scintigraphy in the reflex sympathetic dystrophy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kozin, F.; Soin, J.S.; Ryan, L.M.; Carrera, G.F.; Wortmann, R.L.

    1981-02-01

    Sixty-four consecutive patients were studied for possible reflex sympathetic dystrophy syndrome (RSDS). They were divided into five groups, based upon specific clinical criteria, and the radiographic and scintigraphic findings in each group were examined. Osteoporosis was the most common radiographic abnormality. Scintigraphic abnormalities were noted in 60% of RSDS patients but in only 7% of the others. These findings included increased blood flow and enhanced periarticular radionuclide activity in the affected extremity. The scan may reflect an active, potentially reversible disorder of local blood flow in RSDS. Furthermore, the scintigraphic patterns may be useful in the diagnosis and in predicting which patients are likely to respond to systemic steroid therapy.

  12. Reflex sympathetic dystrophy: an enigmatic improvement with spinal manipulation

    Science.gov (United States)

    Bortolotto, James

    2000-01-01

    Reflex Sympathetic Dystrophy (RSD) or complex regional pain syndrome, is an extremely painful and disabling condition commonly seen following trauma. Its early recognition and treatment is most critical for a favorable prognosis. Although its diagnosis and treatments vary, neuroblockade is the treatment of choice. Very little has been reported in the literature in regards to manipulation as an early treatment modality to improve joint mobility and reduce pain and future disability. This case report reviews one case presentation of RSD where dramatic results followed cervical spine manipulation.

  13. Sympathetic nerve activity and whole body heat stress in humans

    OpenAIRE

    Low, David A.; Keller, David M.; Wingo, Jonathan E.; Brothers, R. Matthew; Crandall, Craig G.

    2011-01-01

    We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ∼0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress. Th...

  14. Memory coherence of a sympathetically cooled trapped-ion qubit

    International Nuclear Information System (INIS)

    Home, J. P.; McDonnell, M. J.; Szwer, D. J.; Keitch, B. C.; Lucas, D. M.; Stacey, D. N.; Steane, A. M.

    2009-01-01

    We demonstrate sympathetic cooling of a 43 Ca + trapped-ion 'memory' qubit by a 40 Ca + 'coolant' ion sufficiently near the ground state of motion for fault-tolerant quantum logic, while maintaining coherence of the qubit. This is an essential ingredient in trapped-ion quantum computers. The isotope shifts are sufficient to suppress decoherence and phase shifts of the memory qubit due to the cooling light which illuminates both ions. We measure the qubit coherence during ten cycles of sideband cooling, finding a coherence loss of 3.3% per cooling cycle. The natural limit of the method is O(10 -4 ) infidelity per cooling cycle.

  15. Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice

    Science.gov (United States)

    Goudy, Kevin; Song, Sihong; Wasserfall, Clive; Zhang, Y. Clare; Kapturczak, Matthias; Muir, Andrew; Powers, Matthew; Scott-Jorgensen, Marda; Campbell-Thompson, Martha; Crawford, James M.; Ellis, Tamir M.; Flotte, Terence R.; Atkinson, Mark A.

    2001-01-01

    The development of spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice provides for their use as a model of human type 1 diabetes. To test the feasibility of muscle-directed gene therapy to prevent type 1 diabetes, we developed recombinant adeno-associated virus (rAAV) vectors containing murine cDNAs for immunomodulatory cytokines IL-4 or IL-10. Skeletal muscle transduction of female NOD mice with IL-10, but not IL-4, completely abrogated diabetes. rAAV-IL-10 transduction attenuated the production of insulin autoantibodies, quantitatively reduced pancreatic insulitis, maintained islet insulin content, and altered splenocyte cytokine responses to mitogenic stimulation. The beneficial effects were host specific, as adoptive transfer of splenocytes from rAAV IL-10-treated animals rapidly imparted diabetes in naive hosts, and the cells contained no protective immunomodulatory capacity, as defined through adoptive cotransfer analyses. These results indicate the utility for rAAV, a vector with advantages for therapeutic gene delivery, to transfer immunoregulatory cytokines capable of preventing type 1 diabetes. In addition, these studies provide foundational support for the concept of using immunoregulatory agents delivered by rAAV to modulate a variety of disorders associated with deleterious immune responses, including allergic reactions, transplantation rejection, immunodeficiencies, and autoimmune disorders. PMID:11717448

  16. Defective Insulin Signalling, Mediated by Inflammation, Connects Obesity to Alzheimer Disease; Relevant Pharmacological Therapies and Preventive Dietary Interventions.

    Science.gov (United States)

    Rodriguez-Casado, Arantxa; Toledano-Díaz, Adolfo; Toledano, Adolfo

    2017-01-01

    Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimer's disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimer's disease. This review relates extensive research literature on facts linking nutrients and dietary patterns to obesity and Alzheimer's disease. In addition briefly presents molecular mechanisms involved in obesity- induced insulin resistance and the contribution of peripheral inflammatory and defective insulin signalling pathways, as well as ectopic lipids accumulation to Alzheimer's development through brain inflammation, neuronal insulin resistance, and cognitive dysfunction seen in Alzheimer's disease. The work relates current and emerging pharmacological and non-pharmacological therapies for the management of obesity, insulin resistance and Alzheimer's considering them as disorders with common molecular features. The findings of this review validate the importance of some nutritional interventions as possible approach to prevent or delay simultaneously progression of Alzheimer's disease and obesity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Does promoting parents' negative attitudes to underage drinking reduce adolescents' drinking? The mediating process and moderators of the effects of the Örebro Prevention Programme.

    Science.gov (United States)

    Özdemir, Metin; Koutakis, Nikolaus

    2016-02-01

    The Örebro Prevention Programme (ÖPP) was found previously to be effective in reducing drunkenness among adolescents [Cohen's d = 0.35, number needed to treat (NNT) = 7.7]. The current study tested the mediating role of parents' restrictive attitudes to underage drinking in explaining the effectiveness of the ÖPP, and the potential moderating role of gender, immigration status, peers' and parents' drinking and parent-adolescent relationship quality. A quasi-experimental matched-control group study with assessments at baseline, and at 18- and 30-month follow-ups. Of the 895 target youths at ages 12-13 years, 811 youths and 651 parents at baseline, 653 youths and 524 parents at 18-month and 705 youths and 506 parents at 30-month follow-up participated in the study. Youths reported on their past month drunkenness, their parents' and peers' alcohol use and the quality of their relationship with parents. Parents reported on their attitudes to underage drinking. The mediation analyses, using latent growth curve modeling, showed that changes in parents' restrictive attitudes to underage drinking explained the impact of the ÖPP on changes in youth drunkenness, which was reduced, and onset of monthly drunkenness, which was delayed, relative to controls. Mediation effect explained 57 and 45% of the effects on drunkenness and onset of monthly drunkenness, respectively. The programme effects on both parents' attitudes and youth drunkenness were similar across gender, immigrant status, parents' and peers' alcohol use and parent-youth relationship quality. Increasing parents' restrictive attitudes to youth drinking appears to be an effective and robust strategy for reducing heavy underage drinking regardless of the adolescents' gender, cultural origin, peers' and parents' drinking and relationship quality with parents. © 2015 Society for the Study of Addiction.

  18. The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.

    Science.gov (United States)

    Kobayashi, Mamoru; Hirooka, Kazuyuki; Ono, Aoi; Nakano, Yuki; Nishiyama, Akira; Tsujikawa, Akitaka

    2017-03-01

    Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.

  19. (In)activity-related neuroplasticity in brainstem control of sympathetic outflow: unraveling underlying molecular, cellular, and anatomical mechanisms

    Science.gov (United States)

    Mischel, Nicholas A.; Subramanian, Madhan; Dombrowski, Maryetta D.; Llewellyn-Smith, Ida J.

    2015-01-01

    More people die as a result of physical inactivity than any other preventable risk factor including smoking, high cholesterol, and obesity. Cardiovascular disease, the number one cause of death in the United States, tops the list of inactivity-related diseases. Nevertheless, the vast majority of Americans continue to make lifestyle choices that are creating a rapidly growing burden of epidemic size and impact on the United States healthcare system. It is imperative that we improve our understanding of the mechanisms by which physical inactivity increases the incidence of cardiovascular disease and how exercise can prevent or rescue the inactivity phenotype. The current review summarizes research on changes in the brain that contribute to inactivity-related cardiovascular disease. Specifically, we focus on changes in the rostral ventrolateral medulla (RVLM), a critical brain region for basal and reflex control of sympathetic activity. The RVLM is implicated in elevated sympathetic outflow associated with several cardiovascular diseases including hypertension and heart failure. We hypothesize that changes in the RVLM contribute to chronic cardiovascular disease related to physical inactivity. Data obtained from our translational rodent models of chronic, voluntary exercise and inactivity suggest that functional, anatomical, and molecular neuroplasticity enhances glutamatergic neurotransmission in the RVLM of sedentary animals. Collectively, the evidence presented here suggests that changes in the RVLM resulting from sedentary conditions are deleterious and contribute to cardiovascular diseases that have an increased prevalence in sedentary individuals. The mechanisms by which these changes occur over time and their impact are important areas for future study. PMID:25957223

  20. Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress

    Science.gov (United States)

    El Sayed, Khadigeh; Macefield, Vaughan G.; Hissen, Sarah L.; Joyner, Michael J.

    2016-01-01

    Key points Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress.In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders.Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven.This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task. Abstract Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post‐exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s−1) compared with positive responders (0.4 ± 0.1 mmHg s−1; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood

  1. Hydralazine tachycardia and sympathetic cardiovascular reactivity in normal subjects.

    Science.gov (United States)

    Vidrio, H; Tena, I

    1980-11-01

    The correlation between hydralazine-induced tachycardia and overall cardiovascular reactivity to sympathetic stimulation was explored in 50 normal subjects. Blood pressure and heart rate changes after standing, immersion of a hand in cold water, the Valsalva maneuver, and moderate exercise were compared with pressure and rate responses to 20 mg oral hydralazine. The drug did not modify blood pressure but increased heart rate, mainly in the standing position. Because plotting the magnitude of this response suggested a two-population distribution, subjects were divided into hyporeactor and hyperreactor groups. Reactivity did not appear to be related to acetylator phenotype. The magnitude of the cardiac response correlated with heart rate responses to standing and to the Valsalva maneuver; when analyzed separately from hyporeactors, correlation was greater among hyperreactors. Because the orthostatic and Valsalva responses are reflex in nature, these results suggest that hydralazine tachycardia is also reflexly induced, that its magnitude depends on individual baroreceptor sensitivity, which is distributed nonnormally, and that it can be predicted by suitable tests of sympathetic responsiveness.

  2. Radiographic study for sympathetic detonation of 500-lb bombs

    Energy Technology Data Exchange (ETDEWEB)

    Lucht, R.A.

    1989-01-01

    Flash radiography have determined the size and velocity vectors in the near field of fragments from tail- and side-initiated MK 82 MOD 1, general-purpose bombs. Excellent radiographs have been acquired from nine separate tests. Unlike arena tests, the radiographs were taken 75 to 125 cm from the case and show that the fragments peel off the case in long strips. A major concern in the design and execution of the experiments was the protection of the 450-kV x-ray heads and the film cassettes from fragments and blast produced by the 500-lb bombs. The velocity and size data, along with optical and electronic pin data, were used to characterize the fragments of the donor bomb in a donor-acceptor sympathetic detonation system study. The bombs were found to contain large shrink voids, randomly located from bomb to bomb, in the explosive Tritonal fill. Characteristics of the fragments from the void side if the bomb were found to be as much as 10% different from the nonvoid side and were much less reproducible than the fragments characteristics of the nonvoid side. The data collected will be useful in evaluating sympathetic detonation mitigation systems designed for use with the bombs. Such mitigation systems may be required for mass storage methods to meet the evolving insensitive munition requirements. 13 refs., 7 figs.

  3. [Complex regional pain syndrome. Reflex sympathetic dystrophy and causalgia].

    Science.gov (United States)

    Baron, R; Binder, A; Ulrich, W; Maier, C

    2002-04-01

    Complex regional pain syndromes (CRPS) occur as the inadequate response to painful trauma in a distal extremity. With CRPS I (sympathetic reflex dystrophy), no lesion of the nerve is present. Aside from sensory disturbances, burning deep spontaneous pain and mechanical allodynia are characteristic. Disturbances in the skin blood circulation, sweating, edema, and trophic disturbances of the skin, joints, and bones are typical. Reduction in muscle strength, tremor, and late dystonic changes comprise the motor disturbances. All symptoms are distributed in the distal extremity and not limited to the region of the peripheral nerves. Complex regional pain syndrome II (causalgia), develops following a partial peripheral nerve lesion. The distally generalized symptoms are identical. Successful therapy depends on an early start of interdisciplinary treatment. In addition to the pain therapy, physiotherapy plays a decisive role in rehabilitation. During the acute phase, freedom from pain at rest and retrogression of the edema must be achieved. With slight spontaneous pain, a conservative therapeutic method may be applied (analgesics, rest, raised position). In case of insufficient improvement and in difficult cases, the effect of intervention (sympathetic blockade) should be tested and possibly a blockade series performed. After reduced spontaneous pain, physiotherapy should be increased stepwise.

  4. [Reflex sympathetic dystrophy: still a poorly defined entity].

    Science.gov (United States)

    Ornetti, Paul; Maillefert, Jean-Francis

    2004-01-31

    The reflex sympathetic dystrophy (algodystrophy) constitutes a large nosological field of which the main characteristics are the appearance of algic and vasomotor symptoms at a segmental level of a limb, in consequence to diverse pathologies (trauma, cardiovascular disease, etc.). The widely accepted theory of a dysregulation of the sympathetic nervous system is nowadays counter-balanced by recent work highlighting the preponderant role of polymodal afferent nerves in the pathophysiology of this disease. The diagnosis, being above-all clinical, is marked by two distinct phases appearing in a variable chronology; a warm phase associating fluctionating pain, stiffness and vasomotor symptoms, and then a cold phase characterized by fibrosis, leading to disabling trophic symptoms. Spontaneous recovery is usual and can be delayed by up to two years, however irreversible sequelae can occur. Paraclinical investigations are necessary to confirm the diagnosis: absence of a biological inflammatory syndrome, early hyperfixation on bone scintography or an abnormality in the MRI signal in the sub-chondral zones. The X-ray shows late local demineralization that is often non-homogenous. The treatment is poorly codified. First-line treatment in France, other than antalgics, often rests on the calcitonins. Intravenous diphosphonates are proposed by some in case of treatment failure. Regional venous blocks are sometimes performed in resistant and disabling forms. Rehabilitation and psychological support have a primordial place throughout the evolution of the illness.

  5. Carotid body (Thermoreceptors, sympathetic neural activation, and cardiometabolic disease

    Directory of Open Access Journals (Sweden)

    Rodrigo Iturriaga

    Full Text Available The carotid body (CB is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.

  6. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    International Nuclear Information System (INIS)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O.; Stefan, L.M.; Stan, R.; Badea, N.; Meghea, A.

    2016-01-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%

  7. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Stefan, L.M. [National Institute of Research and Development for Biological Sciences, Splaiul Independentei Street No. 296, 060031 Bucharest (Romania); Stan, R. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Badea, N., E-mail: nicoleta.badea@gmail.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania)

    2016-07-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%.

  8. Role of the carbohydrate-binding sites of griffithsin in the prevention of DC-SIGN-mediated capture and transmission of HIV-1.

    Directory of Open Access Journals (Sweden)

    Bart Hoorelbeke

    Full Text Available BACKGROUND: The glycan-targeting C-type DC-SIGN lectin receptor is implicated in the transmission of the human immunodeficiency virus (HIV by binding the virus and transferring the captured HIV-1 to CD4(+ T lymphocytes. Carbohydrate binding agents (CBAs have been reported to block HIV-1 infection. We have now investigated the potent mannose-specific anti-HIV CBA griffithsin (GRFT on its ability to inhibit the capture of HIV-1 to DC-SIGN, its DC-SIGN-directed transmission to CD4(+ T-lymphocytes and the role of the three carbohydrate-binding sites (CBS of GRFT in these processes. FINDINGS: GRFT inhibited HIV-1(IIIB infection of CEM and HIV-1(NL4.3 infection of C8166 CD4(+ T-lymphocytes at an EC50 of 0.059 and 0.444 nM, respectively. The single mutant CBS variants of GRFT (in which a key Asp in one of the CBS was mutated to Ala were about ∼20 to 60-fold less potent to prevent HIV-1 infection and ∼20 to 90-fold less potent to inhibit syncytia formation in co-cultures of persistently HIV-1 infected HuT-78 and uninfected C8166 CD4(+ T-lymphocytes. GRFT prevents DC-SIGN-mediated virus capture and HIV-1 transmission to CD4(+ T-lymphocytes at an EC50 of 1.5 nM and 0.012 nM, respectively. Surface plasmon resonance (SPR studies revealed that wild-type GRFT efficiently blocked the binding between DC-SIGN and immobilized gp120, whereas the point mutant CBS variants of GRFT were ∼10- to 15-fold less efficient. SPR-analysis also demonstrated that wild-type GRFT and its single mutant CBS variants have the capacity to expel bound gp120 from the gp120-DC-SIGN complex in a dose dependent manner, a property that was not observed for HHA, another mannose-specific potent anti-HIV-1 CBA. CONCLUSION: GRFT is inhibitory against HIV gp120 binding to DC-SIGN, efficiently prevents DC-SIGN-mediated transfer of HIV-1 to CD4(+ T-lymphocytes and is able to expel gp120 from the gp120-DC-SIGN complex. Functionally intact CBS of GRFT are important for the optimal action of

  9. Central Methysergide Prevents Renal Sympathoinhibition and Bradycardia during Hypotensive Hemorrhage

    Science.gov (United States)

    Veelken, Roland; Johnson, Kim; Scrogin, Karie E.

    1998-01-01

    Central methysergide prevents renal sympathoinhibition and bradycardia during hypotensive hemorrhage. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured in conscious rats during either hemorrhage or cardiopulmonary receptor stimulation with phenylbiguanide (PBG) after intracerebroventricular injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (40 microg). Progressive hemorrhage caused an initial rise (109 +/- 33%) followed by a fall in RSNA (-60 +/- 7%) and a fall in HR (-126 +/- 7 beats/min). Methysergide delayed the hypotension and prevented both the sympathoinhibitory and bradycardic responses to hemorrhage. Systemic 5-HT3-receptor blockade did not influence responses to hemorrhage. The PBG infusion caused transient depressor(-25 +/- 6 mmHg), bradycardic (-176 +/- 40 beats/min), and renal sympathostimulatory (182 +/-47% baseline) responses that were not affected by central methysergide (-20 +/- 6 mmHg, -162 +/- 18 beats/min, 227 +/- 46% baseline). These data indicate that a central serotonergic receptor-mediated component contributes to the sympathoinhibitory and bradycardic responses to hypotensive hemorrhage in conscious rats. Furthermore, the same central 5-HT-receptor populations involved in reflex responses to hypotensive hemorrhage probably do not mediate the sympathoinhibitory response to cardiopulmonary chemosensitive 5-HT3 receptors.

  10. Taurine Pretreatment Prevents Isoflurane-Induced Cognitive Impairment by Inhibiting ER Stress-Mediated Activation of Apoptosis Pathways in the Hippocampus in Aged Rats.

    Science.gov (United States)

    Zhang, Yanan; Li, Dongliang; Li, Haiou; Hou, Dailiang; Hou, Jingdong

    2016-10-01

    Isoflurane, a commonly used inhalation anesthetic, may induce neurocognitive deficits, especially in elderly patients after surgery. Recent study demonstrated that isoflurane caused endoplasmic reticulum (ER) stress and subsequent neuronal apoptosis in the brain, contributing to cognitive deficits. Taurine, a major intracellular free amino acid, has been shown to inhibit ER stress and neuronal apoptosis in several neurological disorders. Here, we examined whether taurine can prevent isoflurane-induced ER stress and cognitive impairment in aged rats. Thirty minutes prior to a 4-h 1.3 % isoflurane exposure, aged rats were treated with vehicle or taurine at low, middle and high doses. Aged rats without any treatment served as control. The brains were harvested 6 h after isoflurane exposure for molecular measurements, and behavioral study was performed 2 weeks later. Compared with control, isoflurane increased expression of hippocampal ER stress biomarkers including glucose-regulated protein 78, phosphorylated (P-) inositol-requiring enzyme 1, P-eukaryotic initiation factor 2-α (EIF2α), activating transcription factor 4 (ATF-4), cleaved ATF-6 and C/EBP homologous protein, along with activation of apoptosis pathways as indicated by decreased B cell lymphoma 2 (BCL-2)/BCL2-associated X protein, increased expressions of cytochrome-c and cleaved caspase-3. Taurine pretreatment dose-dependently inhibited isoflurane-induced increase in expression of ER stress biomarkers except for P-EIF2α and ATF-4, and reversed isoflurane-induced changes in apoptosis-related proteins. Moreover, isoflurane caused spatial working memory deficits in aged rats, which were prevented by taurine pretreatment. The results indicate that taurine pretreatment prevents anesthetic isoflurane-induced cognitive impairment by inhibiting ER stress-mediated activation of apoptosis pathways in the hippocampus in aged rats.

  11. Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2.

    Science.gov (United States)

    Ting, Harold J; Deep, Gagan; Jain, Anil K; Cimic, Adela; Sirintrapun, Joseph; Romero, Lina M; Cramer, Scott D; Agarwal, Chapla; Agarwal, Rajesh

    2015-09-01

    Tumor microenvironment (TM) is an essential element in prostate cancer (PCA), offering unique opportunities for its prevention. TM includes naïve fibroblasts that are recruited by nascent neoplastic lesion and altered into 'cancer-associated fibroblasts' (CAFs) that promote PCA. A better understanding and targeting of interaction between PCA cells and fibroblasts and inhibiting CAF phenotype through non-toxic agents are novel approaches to prevent PCA progression. One well-studied cancer chemopreventive agent is silibinin, and thus, we examined its efficacy against PCA cells-mediated differentiation of naïve fibroblasts into a myofibroblastic-phenotype similar to that found in CAFs. Silibinin's direct inhibitory effect on the phenotype of CAFs derived directly from PCA patients was also assessed. Human prostate stromal cells (PrSCs) exposed to control conditioned media (CCM) from human PCA PC3 cells showed more invasiveness, with increased alpha-smooth muscle actin (α-SMA) and vimentin expression, and differentiation into a phenotype we identified in CAFs. Importantly, silibinin (at physiologically achievable concentrations) inhibited α-SMA expression and invasiveness in differentiated fibroblasts and prostate CAFs directly, as well as indirectly by targeting PCA cells. The observed increase in α-SMA and CAF-like phenotype was transforming growth factor (TGF) β2 dependent, which was strongly inhibited by silibinin. Furthermore, induction of α-SMA and CAF phenotype by CCM were also strongly inhibited by a TGFβ2-neutralizing antibody. The inhibitory effect of silibinin on TGFβ2 expression and CAF-like biomarkers was also observed in PC3 tumors. Together, these findings highlight the potential usefulness of silibinin in PCA prevention through targeting the CAF phenotype in the prostate TM. © 2014 Wiley Periodicals, Inc.

  12. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  13. Cardiac sympathetic nervous system imaging with (123)I-meta-iodobenzylguanidine: Perspectives from Japan and Europe

    NARCIS (Netherlands)

    Nakajima, K.; Scholte, A.; Nakata, T.; Dimitriu-Leen, A.C.; Chikamori, T.; Vitola, J.V.; Yoshinaga, K.

    2017-01-01

    Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging,

  14. Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies

    DEFF Research Database (Denmark)

    Henriksen, J H; Ring-Larsen, H; Christensen, N J

    1985-01-01

    in this condition. This may especially apply to the sympathetic tone in the kidney, as evaluated by regional measurements of noradrenaline overflow. Hepatic elimination of catecholamines is only slightly reduced. Activation of the sympathetic nervous system seems to play an important role in the avid sodium-water...

  15. Arrhythmogenic effect of sympathetic histamine in mouse hearts subjected to acute ischemia.

    Science.gov (United States)

    He, Gonghao; Hu, Jing; Li, Teng; Ma, Xue; Meng, Jingru; Jia, Min; Lu, Jun; Ohtsu, Hiroshi; Chen, Zhong; Luo, Xiaoxing

    2012-02-10

    The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell-deficient mice (MCDM) and histidine decarboxylase knockout (HDC(-/-)) mice were used to exclude the potential involvement of mast cells. Electrical field stimulation and acute ischemia-reperfusion evoked chemical sympathectomy-sensitive histamine release from the hearts of both MCDM and wild-type (WT) mice but not from HDC(-/-) mice. The release of histamine from the hearts of MCDM and WT mice was associated with the development of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. The incidence and duration of induced ventricular arrhythmias were found to decrease in the presence of the selective histamine H(2) receptor antagonist famotidine. Additionally, the released histamine facilitated the arrhythmogenic effect of simultaneously released norepinephrine. We conclude that, under acute ischemic conditions, cardiac sympathetic histamine released by overactive sympathetic nerve terminals plays a certain arrhythmogenic role via H(2) receptors. These findings provided novel insight into the pathophysiological roles of sympathetic histamine, which may be a new therapeutic target for acute ischemia-induced arrhythmias.

  16. Reflex sympathetic dystrophy in a child; Wspolczulna dystrofia odruchowa u dziecka

    Energy Technology Data Exchange (ETDEWEB)

    Napiontek, M.; Krasny, I. [Akademia Medyczna, Poznan (Poland)

    1993-12-31

    A case of reflex sympathetic dystrophy in 11 years old girl was described. The acute pain of the left food was preceded by loss of consciousness of unknown origin. Patchy osteopenia, very rare and non characteristic X-ray changes in children`s reflex sympathetic dystrophy, was observed, mimicking osteomyelitis, bone malignant tumor or Sudeck disease. (author). 5 refs, 2 figs.

  17. Reflex sympathetic dystrophy associated with squamous cell carcinoma of the lung.

    Science.gov (United States)

    Prowse, M; Higgs, C M; Forrester-Wood, C; McHugh, N

    1989-01-01

    Reflex sympathetic dystrophy was the presenting feature in an otherwise occult case of non-metastatic squamous cell carcinoma of the lung which improved on surgical removal of the primary tumour. Reflex sympathetic dystrophy, therefore, should be considered an occasional manifestation of a paraneoplastic syndrome warranting a thorough search for underlying malignancy. Images PMID:2712617

  18. The Sympathetic Release Test: A Test Used to Assess Thermoregulation and Autonomic Control of Blood Flow

    Science.gov (United States)

    Tansey, E. A.; Roe, S. M.; Johnson, C. J.

    2014-01-01

    When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the…

  19. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia A. Thorp

    2015-01-01

    Full Text Available Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS. Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.

  20. Sympathetic Vasoconstrictor Responsiveness of the Leg Vasculature During Experimental Endotoxemia and Hypoxia in Humans

    DEFF Research Database (Denmark)

    Brassard, Patrice; Zaar, Morten; Thaning, Pia

    2016-01-01

    OBJECTIVE: Sympathetic vasoconstriction regulates peripheral circulation and controls blood pressure, but sepsis is associated with hypotension. We evaluated whether apparent loss of sympathetic vasoconstrictor responsiveness relates to distended smooth muscles or to endotoxemia and/or hypoxia......: Endotoxemia increased body temperature from 36.9 ± 0.4°C to 38.6 ± 0.5°C (p

  1. Angiotensin II in the paraventricular nucleus stimulates sympathetic outflow to the cardiovascular system and make vasopressin release in rat.

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Nasimi, Ali

    2016-10-06

    The hypothalamic paraventricular nucleus (PVN) plays essential roles in neuroendocrine and autonomic functions, including cardiovascular regulation. It was shown that microinjection of angiotensin II (AngII) into the PVN produced a pressor response. In this study, we explored the probable mechanisms of this pressor response. AngII was microinjected into the PVN and cardiovascular responses were recorded. Then, the responses were re-tested after systemic injection of a ganglionic blocker, Hexamethonium, or a vasopressin V1 receptor blocker. Hexamethonium pretreatment (i.v.) greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that the sympathetic system is involved in the cardiovascular effect of AngII in the PVN. Systemic pretreatment (i.v.) with V1 antagonist greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that vasopressin release is involved in the cardiovascular effect of AngII in the PVN. Overall, we found that AngII microinjected into the PVN produced a pressor response mediated by the sympathetic system and vasopressin release, indicating that other than circulating AngII, endogenous AngII of the PVN increases the vasopressin release from the PVN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Simultaneous storage of lithium and cesium in a quasi-electrostatic dipole trap. Spinchanging collisions and sympathetic evaporation

    International Nuclear Information System (INIS)

    Wohlleben, W.

    2000-01-01

    This work reports on both inelastic and elastic cold ground state collisions of cesium (Cs) and lithium (Li) in the conservative potential of a quasi-electrostatic optical dipole trap. We make for the first time dedicated measurements of the ground state interaction between atoms of different elements. We study the process of thermalisation by sympathetic cooling in a finite potential. We determine the rate coefficients of hyperfine-changing collisions with regard to three different processes: homonuclear collisions of Cs with Cs, with both of them being in the upper hyperfine ground state; equally for collisions of Li with Li, with both of them being in the upper hyperfine state. For the first time an estimate of the heteronuclear rate coefficient could be given for the collision of Cs in the (F = 4) state with Li in the (F = 1) ground state. We find that elastic interaction in the atomic ground state leads to fast particle losses of Li, which is initially the less abundant in the trap. After transfer into the trap, the Li athermically occupies high energy states just beneath the trap edge. With the well known small LiLi scattering rate alone the distribution cannot thermalize. We believe that LiCs collisions mediate Li thermalisation and subsequent evaporation. The sympathetic evaporation of Li carries away part of the energy of the combined ensemble. We have first experimental indication that this process can cool further down the initially colder of the two gases. (orig.)

  3. Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Sarvari Velaga

    Full Text Available In our previous work we could identify defects in human regulatory T cells (Tregs likely favoring the development of graft-versus-host disease (GvHD following allogeneic stem cell transplantation (SCT. Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.

  4. Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fengbo [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Graduate School of Tianjin Medical University, No. 22, Qixiangtai Street, Heping District, Tianjin 300070 (China); Sun, Xiaolei; Ma, Jianxiong [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Ma, Xinlong, E-mail: gengxiao502@163.com [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Zhao, Bin; Zhang, Yang; Tian, Peng [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Li, Yanjun [Graduate School of Tianjin Medical University, No. 22, Qixiangtai Street, Heping District, Tianjin 300070 (China); Han, Zhe [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China)

    2014-09-26

    Highlights: • Naringin possesses many pharmacological activities, promotes the proliferation of osteoblast. • Undecalcified histological obtain dynamic parameters of callus formation and remodeling. • Naringin regulate osteoclast apoptosis by mitochondrial pathway. - Abstract: Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.

  5. Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway

    International Nuclear Information System (INIS)

    Li, Fengbo; Sun, Xiaolei; Ma, Jianxiong; Ma, Xinlong; Zhao, Bin; Zhang, Yang; Tian, Peng; Li, Yanjun; Han, Zhe

    2014-01-01

    Highlights: • Naringin possesses many pharmacological activities, promotes the proliferation of osteoblast. • Undecalcified histological obtain dynamic parameters of callus formation and remodeling. • Naringin regulate osteoclast apoptosis by mitochondrial pathway. - Abstract: Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats

  6. Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy.

    Directory of Open Access Journals (Sweden)

    Angelica Vaccaro

    Full Text Available BACKGROUND: The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC remains unknown but a role for sympathetic hyperactivity has been suggested. Up to now, no direct evidence of sympathetic nerve hyperactivity has been established nor involvement of sympathetic baroreflex identified. The aim of our study was to determine, by direct sympathetic nerve activity (SNS recording if sympathetic nervous system activity is increased and spontaneous baroreflex control of sympathetic activity reduced in patients with TTC. METHODS: We included 13 patients who presented with TTC and compared their SNS activity and spontaneous baroreflex control of sympathetic activity with that of 13 control patients with acutely decompensated chronic heart failure. SNS activity was evaluated by microneurography, a technique assessing muscle sympathetic nerve activity (MSNA. Spontaneous baroreflex control of sympathetic activity was evaluated as the absolute value of the slope of the regression line representing the relationship between spontaneous diastolic blood pressure values and concomitant SNS activity. Control patients were matched for age, sex, left ventricular ejection fraction and creatinine clearance. RESULTS: The mean age of the patients with TTC was 80 years, all patients were women. There were no significant differences between the two groups of patients for blood pressure, heart rate or oxygen saturation level. TTC patients presented a significant increase in sympathetic nerve activity (MSNA median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7 bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089 and a decrease in spontaneous baroreflex control of sympathetic activity compared to matched control patients (spontaneous baroreflex control of sympathetic activity median 0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg [interquartile range 1.8 to 2.9]; p = 0.005. CONCLUSIONS: We report for the first time, through

  7. Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy.

    Science.gov (United States)

    Vaccaro, Angelica; Despas, Fabien; Delmas, Clement; Lairez, Olivier; Lambert, Elisabeth; Lambert, Gavin; Labrunee, Marc; Guiraud, Thibaut; Esler, Murray; Galinier, Michel; Senard, Jean Michel; Pathak, Atul

    2014-01-01

    The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC) remains unknown but a role for sympathetic hyperactivity has been suggested. Up to now, no direct evidence of sympathetic nerve hyperactivity has been established nor involvement of sympathetic baroreflex identified. The aim of our study was to determine, by direct sympathetic nerve activity (SNS) recording if sympathetic nervous system activity is increased and spontaneous baroreflex control of sympathetic activity reduced in patients with TTC. We included 13 patients who presented with TTC and compared their SNS activity and spontaneous baroreflex control of sympathetic activity with that of 13 control patients with acutely decompensated chronic heart failure. SNS activity was evaluated by microneurography, a technique assessing muscle sympathetic nerve activity (MSNA). Spontaneous baroreflex control of sympathetic activity was evaluated as the absolute value of the slope of the regression line representing the relationship between spontaneous diastolic blood pressure values and concomitant SNS activity. Control patients were matched for age, sex, left ventricular ejection fraction and creatinine clearance. The mean age of the patients with TTC was 80 years, all patients were women. There were no significant differences between the two groups of patients for blood pressure, heart rate or oxygen saturation level. TTC patients presented a significant increase in sympathetic nerve activity (MSNA median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7 bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089) and a decrease in spontaneous baroreflex control of sympathetic activity compared to matched control patients (spontaneous baroreflex control of sympathetic activity median 0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg [interquartile range 1.8 to 2.9]; p = 0.005). We report for the first time, through direct measurement of sympathetic nerve activity, that

  8. Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.

    Science.gov (United States)

    Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C

    2014-01-01

    Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

  9. [Reflex sympathetic dystrophy involving the ankle in pregnancy: characteristics and therapeutic management].

    Science.gov (United States)

    Sergent, F; Mouroko, D; Sellam, R; Marpeau, L

    2003-06-01

    We report the case of a multigravida presenting in the first trimester of pregnancy with reflex sympathetic dystrophy involving both ankles. Preferential location of reflex sympathetic dystrophy in pregnancy is classically the hip (9 times out of 10). Symptoms develop mostly with primipara in the third trimester of pregnancy or in post-partum. Fracture is the major risk of reflex sympathetic dystrophy. Peculiarities of reflex sympathetic dystrophy's treatment in the course of pregnancy are evoked. The end of the pregnancy can be shortened with the aim of stabilizing disease even to activate its healing. Pathophysiologic mechanisms of reflex sympathetic dystrophy in pregnancy seem multiple and complex. Our observation, by its atypical characteristics, recalls it.

  10. Protective phenotypes of club cells and alveolar macrophages are favored as part of endotoxin-mediated prevention of asthma

    Science.gov (United States)

    García, Luciana N; Leimgruber, Carolina; Uribe Echevarría, Elisa M; Acosta, Patricio L; Brahamian, Jorge M; Polack, Fernando P; Miró, María S; Quintar, Amado A; Sotomayor, Claudia E

    2014-01-01

    Atopic asthma is a chronic allergic disease that involves T-helper type 2 (Th2)-inflammation and airway remodeling. Bronchiolar club cells (CC) and alveolar macrophages (AM) are sentinel cells of airway barrier against inhaled injuries, where allergy induces mucous metaplasia of CC and the alternative activation of AM, which compromise host defense mechanisms and amplify Th2-inflammation. As there is evidence that high levels of environmental endotoxin modulates asthma, the goal of this study was to evaluate if the activation of local host defenses by Lipopolysaccharide (LPS) previous to allergy development can contribute to preserving CC and AM protective phenotypes. Endotoxin stimulus before allergen exposition reduced hallmarks of allergic inflammation including eosinophil influx, Interleukin-4 and airway hyperreactivity, while the T-helper type 1 related cytokines IL-12 and Interferon-γ were enhanced. This response was accompanied by the preservation of the normal CC phenotype and the anti-allergic proteins Club Cell Secretory Protein (CCSP) and Surfactant-D, thereby leading to lower levels of CC metaplasia and preventing the increase of the pro-Th2 cytokine Thymic stromal lymphopoietin. In addition, classically activated alveolar macrophages expressing nitric oxide were promoted over the alternatively activated ones that expressed arginase-1. We verified that LPS induced a long-term overexpression of CCSP and the innate immune markers Toll-like receptor 4, and Tumor Necrosis Factor-α, changes that were preserved in spite of the allergen challenge. These results demonstrate that LPS pre-exposition modifies the local bronchioalveolar microenvironment by inducing natural anti-allergic mechanisms while reducing local factors that drive Th2 type responses, thus modulating allergic inflammation. PMID:25504013

  11. Extensive protein hydrolyzation is indispensable to prevent IgE-mediated poultry allergen recognition in dogs and cats.

    Science.gov (United States)

    Olivry, Thierry; Bexley, Jennifer; Mougeot, Isabelle

    2017-08-17

    similar to that of the beef meat negative control. Altogether, these results suggest that an extensive-but not partial-hydrolyzation of the poultry feather extract is necessary to prevent the recognition of allergenic epitopes by poultry-specific IgE.

  12. Production and sympathetic cooling of complex molecular ions

    International Nuclear Information System (INIS)

    Zhang, Chaobo

    2008-01-01

    This thesis reports on experimental and theoretical studies of the sympathetic cooling of complex molecular ions demonstrating that this general method for cooling atomic and molecular ions is reliable and efficient. For this purpose, complex molecular ions and barium ions have been confined simultaneously in a linear Paul trap. The complex molecular ions are generated in an electrospray ionization system and transferred to the trap via a 2 m long octopole ion guide. These molecular ions are pre-cooled by room temperature helium buffer gas so that they can be captured by the trap. The atomic barium ions are loaded from a barium evaporator oven and are laser-cooled by a 493 nm cooling laser and a 650 nm repumping laser. Due to the mutual Coulomb interaction among these charged particles, the kinetic energy of the complex molecular ions can be reduced significantly. In our experiments we have demonstrated the sympathetic cooling of various molecules (CO 2 , Alexa Fluor 350, glycyrrhetinic acid, cytochrome c) covering a wide mass range from a few tens to 13000 amu. In every case the molecular ions could be cooled down to millikelvin temperatures. Photo-chemical reactions of the 138 Ba + ions in the ( 2 P 1/2 ) excited state with gases such as O 2 , CO 2 , or N 2 O, could be observed. If the initial 138 Ba + ion ensemble is cold, the produced 138 BaO + ions are cold as well, with a similar temperature as the laser-cooled barium ions (a few tens of millikelvin). The back-reaction of 138 BaO + ions with neutral CO to 138 Ba + is possible and was observed in our experiments as well. A powerful molecular dynamics (MD) simulation program has been developed. With this program dynamic properties of ion ensembles, such as sympathetic interactions or heating effects, have been investigated and experimental results have been analyzed to obtain, for example, ion numbers and temperatures. Additionally, the feasibility of nondestructive spectroscopy via an optical dipole excitation

  13. Production and sympathetic cooling of complex molecular ions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chaobo

    2008-06-24

    This thesis reports on experimental and theoretical studies of the sympathetic cooling of complex molecular ions demonstrating that this general method for cooling atomic and molecular ions is reliable and efficient. For this purpose, complex molecular ions and barium ions have been confined simultaneously in a linear Paul trap. The complex molecular ions are generated in an electrospray ionization system and transferred to the trap via a 2 m long octopole ion guide. These molecular ions are pre-cooled by room temperature helium buffer gas so that they can be captured by the trap. The atomic barium ions are loaded from a barium evaporator oven and are laser-cooled by a 493 nm cooling laser and a 650 nm repumping laser. Due to the mutual Coulomb interaction among these charged particles, the kinetic energy of the complex molecular ions can be reduced significantly. In our experiments we have demonstrated the sympathetic cooling of various molecules (CO{sub 2}, Alexa Fluor 350, glycyrrhetinic acid, cytochrome c) covering a wide mass range from a few tens to 13000 amu. In every case the molecular ions could be cooled down to millikelvin temperatures. Photo-chemical reactions of the {sup 138}Ba{sup +} ions in the ({sup 2}P{sub 1/2}) excited state with gases such as O{sub 2}, CO{sub 2}, or N{sub 2}O, could be observed. If the initial {sup 138}Ba{sup +} ion ensemble is cold, the produced {sup 138}BaO{sup +} ions are cold as well, with a similar temperature as the laser-cooled barium ions (a few tens of millikelvin). The back-reaction of {sup 138}BaO{sup +} ions with neutral CO to {sup 138}Ba{sup +} is possible and was observed in our experiments as well. A powerful molecular dynamics (MD) simulation program has been developed. With this program dynamic properties of ion ensembles, such as sympathetic interactions or heating effects, have been investigated and experimental results have been analyzed to obtain, for example, ion numbers and temperatures. Additionally, the

  14. Gender Differences in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia

    Directory of Open Access Journals (Sweden)

    Yujuan Wang

    2014-01-01

    Full Text Available Vogt-Koyanagi-Harada disease (VKH and sympathetic ophthalmia (SO are types of T-cell mediated autoimmune granulomatous uveitis. Although the two diseases share common clinical features, they have certain differences in gender predilections. VKH classically has been reported as more prevalent in females than males, yet some studies in Japan and China have not found differences in gender prevalence. Male patients have a higher risk of chorioretinal degeneration, vitiligo, and worse prognosis. Conversely, the changing levels of estrogen/progesterone during pregnancy and the menstrual cycle as well as higher levels of TGF-β show a protective role in females. Potential causes of female predilection for VKH are associated with HLA-DR and HLA-DQ alleles. SO, a bilateral granulomatous uveitis, occurs in the context of one eye after a penetrating injury due to trauma or surgery. In contrast to the female dominance in VKH, males are more frequently affected by SO due to a higher incidence of ocular injury, especially during wartime. However, no gender predilection of SO has been reported in postsurgical cases. No clinically different manifestations are revealed between males and females in SO secondary to either ocular trauma or surgery. The potential causes of the gender difference may provide hints on future treatment and disease evaluation.

  15. Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

    Science.gov (United States)

    Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique

    2018-03-01

    Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. [The renin-angiotensin system and the sympathetic nervous system in essential hypertension].

    Science.gov (United States)

    Vincent, M; Milon, H; Revol, T; Annat, G; Froment, A; Sassard, J; Cier, J F

    1982-06-01

    In 112 patients with essential hypertension (HTA), free of any therapeutic and receiving the standard ward, a significant inverse relationship was found between age and plasma renin activity (PRA) and plasma aldosterone (PA), measured in the supine and upright position. Urinary epinephrine and norepinephrine were not related with age. When dividing the patients in 4 different age groups, it appeared that those younger than 30 years exhibited a significantly higher PRA and PA values and a higher frequency of borderline hypertension (45 p. 100) than the older ones (12 p. 100). So as to determine the characteristics associated with borderline HTA, it was necessary to eliminate the influence of age. This was achieved by comparing two groups of carefully age-matched patients, one with borderline HTA and the other with stable HTA. The only significant difference found was a significantly more marked increase in PRA in response to orthostatism, in patients with borderline HTA. Since renin responses to an orthostatic stress are largely mediated by renal nerves, this result suggest that borderline HTA could be associated with an increased reactivity of the sympathetic nervous system.

  17. Prospects for sympathetic cooling of optically stark decelerated molecules

    Science.gov (United States)

    Barletta, Paolo; Tennyson, Jonathan; Barker, Peter F.

    2009-05-01

    A novel approach has recently been proposed for producing ultra-cold molecules by sympathetic cooling with optically co-trapped rare gas (Rg) atoms [1]. For an efficient planning and realization of the experiment theoretical determination of atom-molecule cross sections at ultra-low energies is very important. In this contribution I will present calculations of scattering lengths and cross sections for he Rg-H2 and Rg-benzene complexes (Rg=He,Ne,Ar,Kr,Xe), with particular emphasis on Ar and Kr. H2 and benzene are considered in their lowest vibrational-rotational states. A direct Monte Carlo simulation of the dynamics of the cooling process has been made by means of the Bird method. This simulation will enable the optimization of the experimental apparatus, and to test the cooling capability of the different Rg gases. [1] P. Barletta, J. Tennyson, P.F. Barker, Phys. Rev. A, 78, 052707 (2008).

  18. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  19. Dynamics of neuro-effector coupling at 'cardiac sympathetic' synapses.

    Science.gov (United States)

    Prando, Valentina; Da Broi, Francesca; Franzoso, Mauro; Plazzo, Anna Pia; Pianca, Nicola; Francolini, Maura; Basso, Cristina; Kay, Matthew W; Zaglia, Tania; Mongillo, Marco

    2018-03-10

    Cardiac sympathetic neurons (SNs) finely tune the rate and strength of heart contractions to match the blood demand, both at rest and during acute stresses, through the release of norepinephrine (NE). Junctional sites at the interface between the two cell types have been observed, but whether direct neuro-cardiac coupling has a role in heart physiology has not thus far been clearly demonstrated. We investigated the dynamics of SN/cardiomyocyte intercellular signalling, both by FRET-based imaging of cAMP in co-cultures, as a readout of cardiac β-AR activation, and in vivo, using optogenetics in transgenic mice with SN-specific expression of Channelrhodopsin-2. We demonstrate that SNs and cardiomyocytes interact at specific sites both in the human and rodent heart, and in co-cultures. Accordingly, neuronal activation elicited intracellular cAMP increases only in directly contacted myocytes and cell-cell coupling utilized a junctional extracellular signalling domain with elevated NE concentration. In the living mouse, optogenetic activation of cardiac SNs innervating the sino-atrial node resulted in an instantaneous chronotropic effect, which shortened the heartbeat interval with single beat precision. Remarkably, inhibition of the optogenetically elicited chronotropic responses required a high dose of propranolol (20-50 mg/Kg), suggesting that sympathetic neurotransmission in the heart occurs at locally elevated NE concentration. Our in vitro and in vivo data suggest that the control of cardiac function, by SNs, occurs via direct intercellular coupling due to the establishment of a specific junctional-site. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

    International Nuclear Information System (INIS)

    Guimarães, Sarita Lígia Pessoa de Melo Machado; Brandão, Simone Cristina Soares; Andrade, Luciana Raposo; Maia, Rafael José Coelho; Markman Filho, Brivaldo

    2015-01-01

    Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 ( 123 I-mIBG) seems to precede the drop in left ventricular ejection fraction. To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline. Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of 123 I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2). Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of 123 I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of 123 I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of 123 I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of 123 I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02). In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with 123 I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity

  1. Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

    Energy Technology Data Exchange (ETDEWEB)

    Guimarães, Sarita Lígia Pessoa de Melo Machado [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Brandão, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Andrade, Luciana Raposo [Hospital Santa Joana, Recife, PE (Brazil); Maia, Rafael José Coelho [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Markman Filho, Brivaldo [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil)

    2015-09-15

    Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 ({sup 123}I-mIBG) seems to precede the drop in left ventricular ejection fraction. To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline. Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2). Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02). In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with {sup 123}I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity.

  2. Sympathetic activation and baroreflex function during intradialytic hypertensive episodes.

    Directory of Open Access Journals (Sweden)

    Dvora Rubinger

    Full Text Available BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI and systolic blood pressure (SBP were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS in the low (LF and high (HF frequency ranges were assessed using the complex demodulation technique (CDM. Intradialytic hypertensive episodes were associated with an increased (n = 45 or decreased (n = 17 heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes

  3. Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Elvas, Filipe; Martins, Tiago; Cunha, Rodrigo A; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-03-01

    Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 μL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.

    Directory of Open Access Journals (Sweden)

    Xu Zhang

    Full Text Available Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs, most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2>0.6 for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.

  5. Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Jianguo Cheng

    2012-01-01

    Full Text Available The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic blocks over a 26-month period provided sustained pain relief in his legs. Additional thoracic paravertebral blocks further provided control of the pain in the trunk which can occasionally be seen in severe diabetic neuropathy cases, consequent to extensive involvement of the intercostal nerves. These blocks provided sustained and significant pain relief and improvement of quality of life over a period of more than two years. We thus provided the first clinical evidence supporting the notion that sympathetic nervous system plays a critical role in painful diabetic neuropathy and sympathetic blocks can be an effective management modality of painful diabetic neuropathy. We concluded that the sympathetic nervous system is a valuable therapeutic target of pharmacological and interventional modalities of treatments in painful diabetic neuropathy patients.

  6. The Nucleus of the Solitary Tract and the coordination of respiratory and sympathetic activities

    Directory of Open Access Journals (Sweden)

    Daniel B. Zoccal

    2014-06-01

    Full Text Available It is well known that breathing introduces rhythmical oscillations in the heart rate and arterial pressure levels. Sympathetic oscillations coupled to the respiratory activity have been suggested as an important homeostatic mechanism optimizing tissue perfusion and blood gas uptake/delivery. This respiratory-sympathetic coupling is strengthened in conditions of blood gas challenges (hypoxia and hypercapnia as a result of the synchronized activation of brainstem respiratory and sympathetic neurons, culminating with the emergence of entrained cardiovascular and respiratory reflex responses. Studies have proposed that the ventrolateral region of the medulla oblongata is a major site of synaptic interaction between respiratory and sympathetic neurons. However, other brainstem regions also play a relevant role in the patterning of respiratory and sympathetic motor outputs. Recent findings suggest that the neurons of the nucleus of the solitary tract (NTS, in the dorsal medulla, are essential for the processing and coordination of respiratory and sympathetic responses to hypoxia. The NTS is the first synaptic station of the cardiorespiratory afferent inputs, including peripheral chemoreceptors, baroreceptors and pulmonary stretch receptors. The synaptic profile of the NTS neurons receiving the excitatory drive from afferent inputs is complex and involves distinct neurotransmitters, including glutamate, ATP and acetylcholine. In the present review we discuss the role of the NTS circuitry in coordinating sympathetic and respiratory reflex responses. We also analyze the neuroplasticity of NTS neurons and their contribution for the development of cardiorespiratory dysfunctions, as observed in neurogenic hypertension, obstructive sleep apnea and metabolic disorders.

  7. Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

    Science.gov (United States)

    Wilson, Thad E

    2017-05-01

    Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures.

    Directory of Open Access Journals (Sweden)

    Dalian Ding

    Full Text Available Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects.In this study, we show that the coenzyme NAD(+, known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+ protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+ reduced the levels of these oxidative stress and apoptosis markers.Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+ suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment.

  9. 1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

    Science.gov (United States)

    Liu, Xiuting; Zhou, Wei; Zhang, Xin; Ding, Yang; Du, Qianming; Hu, Rong

    2018-04-01

    Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC. © 2018 UICC.

  10. Smoking-associated lung cancer prevention by blockade of the beta-adrenergic receptor-mediated insulin-like growth factor receptor activation.

    Science.gov (United States)

    Min, Hye-Young; Boo, Hye-Jin; Lee, Ho Jin; Jang, Hyun-Ji; Yun, Hye Jeong; Hwang, Su Jung; Smith, John Kendal; Lee, Hyo-Jong; Lee, Ho-Young

    2016-10-25

    Activation of receptor tyrosine kinases (RTKs) is associated with carcinogenesis, but its contribution to smoking-associated lung carcinogenesis is poorly understood. Here we show that a tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced insulin-like growth factor 1 receptor (IGF-1R) activation via β-adrenergic receptor (β-AR) is crucial for smoking-associated lung carcinogenesis. Treatment with NNK stimulated the IGF-1R signaling pathway in a time- and dose-dependent manner, which was suppressed by pharmacological or genomic blockade of β-AR and the downstream signaling including a Gβγ subunit of β-AR and phospholipase C (PLC). Consistently, β-AR agonists led to increased IGF-1R phosphorylation. The increase in IGF2 transcription via β-AR, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-kappa B (NF-κB) was associated with NNK-induced IGF-1R activation. Finally, treatment with β-AR antagonists suppressed the acquisition of transformed phenotypes in lung epithelial cells and lung tumor formation in mice. These results suggest that blocking β-AR-mediated IGF-1R activation can be an effective strategy for lung cancer prevention in smokers.

  11. Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures.

    Science.gov (United States)

    Ding, Dalian; Qi, Weidong; Yu, Dongzhen; Jiang, Haiyan; Han, Chul; Kim, Mi-Jung; Katsuno, Kana; Hsieh, Yun Hua; Miyakawa, Takuya; Salvi, Richard; Tanokura, Masaru; Someya, Shinichi

    2013-01-01

    Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects. In this study, we show that the coenzyme NAD(+), known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+) protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+) reduced the levels of these oxidative stress and apoptosis markers. Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+) suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment.

  12. Substitution of the precursor peptide prevents anti-prM antibody-mediated antibody-dependent enhancement of dengue virus infection.

    Science.gov (United States)

    Wang, Ying; Si, Lu-Lu; Guo, Xiao-Lan; Cui, Guo-Hui; Fang, Dan-Yun; Zhou, Jun-Mei; Yan, Hui-Jun; Jiang, Li-Fang

    2017-02-02

    Antibody-dependent enhancement (ADE) is currently considered as the mechanism underlying the pathogenesis of severe dengue disease. Many studies have shown that precursor (pr) peptide-specific antibodies do not efficiently neutralize infection but potently promote ADE of dengue virus (DENV) infection. To explore the effect of pr peptide substitution on neutralization and ADE of DENV infection, the rabbit anti-prM polyclonal antibodies (pAbs) and anti-JEVpr/DENV-M pAbs were prepared, and the neutralization and ADE of these two pAbs were further compared. Here, we report that both anti-JEVpr/DENV-M and anti-prM pAbs exhibited broad cross-reactivity and only partial neutralization with four DENV serotypes and immature DENV. Rabbit anti-prM pAbs showed a significant enhancement in a broad range of serum dilutions. However, there was no statistically significant difference in the enhancing activity of rabbit anti-JEVpr/DENV-M pAbs at various levels of dilution. These results demonstrate that anti-prM antibody-mediated ADE can be prevented by JEV pr peptide replacement. The present study contribute further to research on the pathogenesis of DENV infection. Copyright © 2016. Published by Elsevier B.V.

  13. Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system.

    Science.gov (United States)

    Molkov, Yaroslav I; Zoccal, Daniel B; Baekey, David M; Abdala, Ana P L; Machado, Benedito H; Dick, Thomas E; Paton, Julian F R; Rybak, Ilya A

    2014-01-01

    Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states. © 2014 Elsevier B.V. All rights reserved.

  14. Vibration sense and sympathetic vasoconstrictor activity in patients with occlusive arterial disease

    DEFF Research Database (Denmark)

    Bjerre-Jepsen, K; Henriksen, O; Parm, Martin Lehnsbo

    1983-01-01

    The function of sympathetic vasoconstrictor fibres was studied in 18 patients with occlusive arterial disease of the legs and somatic neuropathy, as evidenced as an increased vibration perception threshold. Nine patients suffered from long-term diabetes mellitus. Sympathetic vasoconstrictor...... of vibration sense, abnormal vasoconstrictor function was found. In three of these patients, the abnormal response most likely could be ascribed to impaired function of the vascular smooth muscle cells. Neither in diabetics nor in non-diabetics could an abnormal vibration sense be taken as evidence for loss...... of sympathetic vasoconstrictor function. It is suggested that this is studied by a simple postural test as used in the present study....

  15. ACE INHIBITION ATTENUATES SYMPATHETIC CORONARY VASOCONSTRICTION IN PATIENTS WITH CORONARY-ARTERY DISEASE

    NARCIS (Netherlands)

    PERONDI, R; SAINO, A; TIO, RA; POMIDOSSI, G; GREGORINI, L; ALESSIO, P; MORGANTI, A; ZANCHETTI, A; MANCIA, G

    Background. In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however. Methods and Results. In nine normotensive

  16. Sympathetic neural adaptation to hypocaloric diet with or without exercise training in obese metabolic syndrome subjects

    DEFF Research Database (Denmark)

    Straznicky, Nora E; Lambert, Elisabeth A; Nestel, Paul J

    2010-01-01

    Sympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function....

  17. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

    NARCIS (Netherlands)

    Kienbaum, P.; Heuter, T.; Michel, M. C.; Peters, J.

    2000-01-01

    BACKGROUND: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent

  18. Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report.

    Science.gov (United States)

    Nwaejike, Nnamdi; Archbold, Hap; Wilson, Darrin S

    2008-06-24

    Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

  19. Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Nwaejike Nnamdi

    2008-06-01

    Full Text Available Abstract Introduction Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. Case presentation We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Conclusion Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

  20. Baroreflex gain and vasomotor sympathetic modulation in resistant hypertension.

    Science.gov (United States)

    Freitas, Isabelle Magalhães Guedes; de Almeida, Leonardo Barbosa; Pereira, Natália Portela; Mira, Pedro Augusto de Carvalho; de Paula, Rogério Baumgratz; Martinez, Daniel Godoy; Toschi-Dias, Edgar; Laterza, Mateus Camaroti

    2017-06-01

    The aim of this study was to determine the gain and latency of arterial baroreflex control of heart rate in patients with resistant hypertension compared to patients with essential hypertension and normotensive subjects. Eighteen patients with resistant hypertension (56 ± 10 years, mean of four antihypertensive drugs), 17 patients with essential hypertension (56 ± 11 years, mean of two antihypertensive drugs), and 17 untreated normotensive controls (50 ± 15 years) were evaluated by spectral analysis of the spontaneous fluctuations of arterial pressure (beat-to-beat) and heart rate (ECG). This analysis estimated vasomotor and cardiac autonomic modulations, respectively. The transfer function analysis quantified the gain and latency of the response of output signal (RR interval) per unit of spontaneous change of input signal (systolic arterial pressure). The gain was similarly lower in patients with resistant hypertension and patients with essential hypertension in relation to normotensive subjects (4.67 ± 2.96 vs. 6.60 ± 3.30 vs. 12.56 ± 8.81 ms/mmHg; P baroreflex control of heart rate was significantly higher only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (-4.01 ± 3.19 vs. -2.91 ± 2.10 vs. -1.82 ± 1.09 s; P = 0.04, respectively). In addition, the index of vasomotor sympathetic modulation was significantly increased only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (4.04 ± 2.86 vs. 2.65 ± 1.88 vs. 2.06 ± 1.70 mmHg 2 ; P baroreflex control of heart rate. These patients also have increased vasomotor sympathetic modulation.

  1. Design methodology for understanding the sympathetic detonation characteristics of insensitive high explosives

    OpenAIRE

    Raghavan, Dinesh.

    2005-01-01

    The understanding of sympathetic detonation of energetic materials is important from the stand point of safety, shelf life, storage requirements and handling. The objective of this thesis is to introduce a methodology to assess performance and sensitivity levels of insensitive munitions to sympathetic detonations. AUTODYN code was utilized to validate the shock sensitivity results for Composition B explosives. Upon code validation, simulations were conducted to evaluate small scale sympat...

  2. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    Science.gov (United States)

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  3. Spinal Cord Injury-Induced Dysautonomia via Plasticity in Paravertebral Sympathetic Postganglionic

    Science.gov (United States)

    2016-10-01

    therefore assume that our new whole cell recordings are closer to physiological reality . (B) Synaptic and anatomical properties of thoracic...2015) Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in...Neurosci. Abst. 42 (2016). 2. Halder, M.C., M.; MacDowell, C.; McKinnon, M.; Sawchuk,M.; Hochman,S. (2016). Anatomy of mouse thoracic sympathetic chain

  4. Causalgic form of postphlebitic syndrome. A variety of reflex sympathetic dystrophy caused by acute deep thrombophlebitis.

    Science.gov (United States)

    Massell, T B

    1988-01-01

    The causalgic form of the postphlebitic syndrome or reflex sympathetic dystrophy resulting from acute deep thrombophlebitis is a relatively uncommon and, unfortunately, frequently unrecognized form of the postphlebitic syndrome. The usual signs of venous insufficiency are minimal, but severe burning pain is characteristic, usually increased by dependency. The diagnosis is confirmed by phlebography and the response to a lumbar sympathetic block. A lumbar sympathectomy produces permanent pain relief. PMID:3176488

  5. Muscle Sympathetic Nerve Activity During Intense Lower Body Negative Pressure to Presyncope in Humans

    Science.gov (United States)

    2009-08-24

    maximal LBNP tolerance. Using this approach , absolute LBNP levels corresponded well to these ranges of percentages if subjects were able to continue at... patients with spinal cord injury display spontaneous bursts of MSNA, but activity is significantly lower than that of neurologically intact patients , and is...over sympathetic neural activity, and that this reduced baroreflex sensitivity is associated with syncope . We reasoned that if sympathetic baroreflexes

  6. Baroreflex physiology studied in healthy subjects with very infrequent muscle sympathetic bursts

    Science.gov (United States)

    Diedrich, André; Crossman, Alexandra A.; Beightol, Larry A.; Tahvanainen, Kari U. O.; Kuusela, Tom A.; Ertl, Andrew C.

    2013-01-01

    Because it is likely that, in healthy human subjects, baroreflex mechanisms operate continuously, independent of experimental interventions, we asked the question, In what ways might study of unprovoked, very infrequent muscle sympathetic bursts inform baroreflex physiology? We closely examined arterial pressure and R-R interval responses of 11 supine healthy young subjects to arterial pressure ramps triggered by large isolated muscle sympathetic bursts. We triggered data collection sweeps on the beginnings of sympathetic bursts and plotted changes of arterial pressure (finger volume clamp or intra-arterial) and R-R intervals occurring before as well as after the sympathetic triggers. We estimated baroreflex gain from regression of R-R intervals on systolic pressures after sympathetic bursts and from the transfer function between cross-spectra of systolic pressure and R-R intervals at low frequencies. Isolated muscle sympathetic bursts were preceded by arterial pressure reductions. Baroreflex gain, calculated with linear regression of R-R intervals on systolic pressures after bursts, was virtually identical to baroreflex gain, calculated with the cross-spectral modulus [mean and (range): 24 (7–43) vs. 24 (8–45) ms/mmHg], and highly significant, according to linear regression (r2 = 0.91, P = 0.001). Our results indicate that 1) since infrequent human muscle sympathetic bursts are almost deterministically preceded by arterial pressure reductions, their occurrence likely reflects simple baroreflex physiology, and 2) the noninvasive low-frequency modulus reliably reproduces gains derived from R-R interval responses to arterial pressure ramps triggered by infrequent muscle sympathetic bursts. PMID:23195626

  7. Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Møller, Søren; Mortensen, Christian; Bendtsen, Flemming

    2012-01-01

    Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in pati......Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake...

  8. Glyceraldehyde-3-Phosphate Dehydrogenase–Monoamine Oxidase B-Mediated Cell Death-Induced by Ethanol is Prevented by Rasagiline and 1-R-Aminoindan

    Science.gov (United States)

    Ou, Xiao-Ming; Lu, Deyin; Johnson, Chandra; Chen, Kevin; Youdim, Moussa B. H.; Rajkowska, Grazyna; Shih, Jean C.

    2010-01-01

    The inhibitors of monoamine oxidase B (MAO B) are effectively used as therapeutic drugs for neuropsychiatric and neurodegenerative diseases. However, their mechanism of action is not clear, since the neuroprotective effect of MAO B inhibitors is associated with the blockage of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-death cascade, rather than the inhibition of MAO B. Here, we provide evidence that GAPDH potentiates the ethanol-induced activity of MAO B and brain cell toxicity. The levels of nuclear GAPDH and MAO B activity are significantly increased in brain-derived cell lines upon 75 mM ethanol-induced cell death. Over-expression of GAPDH in cells enhances ethanol-induced cell death, and also increases the ethanol-induced activation of MAO B. In contrast, the MAO B inhibitors rasagiline and selegiline (0.25 nM) and the rasagiline metabolite, 1-R-aminoindan (1 μM) decreases the ethanol-induced MAO B, prevents nuclear translocation of GAPDH and reduces cell death. In addition, GAPDH interacts with transforming growth factor-beta-inducible early gene (TIEG2), a transcriptional activator for MAO B, and this interaction is increased in the nucleus by ethanol but reduced by MAO B inhibitors and 1-R-aminoindan. Furthermore, silencing TIEG2 using RNAi significantly reduces GAPDH-induced MAO B upregulation and neurotoxicity. In summary, ethanol-induced cell death, attenuated by MAO B inhibitors, may result from disrupting the movement of GAPDH with the transcriptional activator into the nucleus and secondly inhibit MAO B gene expression. Thus, the neuroprotective effects of rasagiline or 1-R-aminoindan on ethanol-induced cell death mediated by a novel GAPDH-MAO B pathway may provide a new insight in the treatment of neurobiological diseases including alcohol-use disorders. PMID:19526291

  9. ACE2-mediated reduction of oxidative stress in the central nervous system is associated with improvement of autonomic function.

    Directory of Open Access Journals (Sweden)

    Huijing Xia

    Full Text Available Oxidative stress in the central nervous system mediates the increase in sympathetic tone that precedes the development of hypertension. We hypothesized that by transforming Angiotensin-II (AngII into Ang-(1-7, ACE2 might reduce AngII-mediated oxidative stress in the brain and prevent autonomic dysfunction. To test this hypothesis, a relationship between ACE2 and oxidative stress was first confirmed in a mouse neuroblastoma cell line (Neuro2A cells treated with AngII and infected with Ad-hACE2. ACE2 overexpression resulted in a reduction of reactive oxygen species (ROS formation. In vivo, ACE2 knockout (ACE2(-/y mice and non-transgenic (NT littermates were infused with AngII (10 days and infected with Ad-hACE2 in the paraventricular nucleus (PVN. Baseline blood pressure (BP, AngII and brain ROS levels were not different between young mice (12 weeks. However, cardiac sympathetic tone, brain NADPH oxidase and SOD activities were significantly increased in ACE2(-/y. Post infusion, plasma and brain AngII levels were also significantly higher in ACE2(-/y, although BP was similarly increased in both genotypes. ROS formation in the PVN and RVLM was significantly higher in ACE2(-/y mice following AngII infusion. Similar phenotypes, i.e. increased oxidative stress, exacerbated dysautonomia and hypertension, were also observed on baseline in mature ACE2(-/y mice (48 weeks. ACE2 gene therapy to the PVN reduced AngII-mediated increase in NADPH oxidase activity and normalized cardiac dysautonomia in ACE2(-/y mice. Altogether, these data indicate that ACE2 gene deletion promotes age-dependent oxidative stress, autonomic dysfunction and hypertension, while PVN-targeted ACE2 gene therapy decreases ROS formation via NADPH oxidase inhibition and improves autonomic function. Accordingly, ACE2 could represent a new target for the treatment of hypertension-associated dysautonomia and oxidative stress.

  10. Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

    Science.gov (United States)

    Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

    2017-08-01

    Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

  11. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

  12. Recovery of sympathetic nerve function after lumbar sympathectomy is slower in the hind limbs than in the torso.

    Science.gov (United States)

    Zheng, Zhi-Fang; Liu, Yi-Shu; Min, Xuan; Tang, Jian-Bing; Liu, Hong-Wei; Cheng, Biao

    2017-07-01

    Local sympathetic denervation by surgical sympathectomy is used in the treatment of lower limb ulcers and ischemia, but the restoration of cutaneous sympathetic nerve functions is less clear. This study aims to explore the recovery of cutaneous sympathetic functions after bilateral L 2-4 sympathectomy. The skin temperature of the left feet, using a point monitoring thermometer, increased intraoperatively after sympathectomy. The cytoplasm of sympathetic neurons contained tyrosine hydroxylase and dopamine β-hydroxylase, visualized by immunofluorescence, indicated the accuracy of sympathectomy. Iodine starch test results suggested that the sweating function of the hind feet plantar skin decreased 2 and 7 weeks after lumbar sympathectomy but had recovered by 3 months. Immunofluorescence and western blot assay results revealed that norepinephrine and dopamine β-hydroxylase expression in the skin from the sacrococcygeal region and hind feet decreased in the sympathectomized group at 2 weeks. Transmission electron microscopy results showed that perinuclear space and axon demyelination in sympathetic cells in the L 5 sympathetic trunks were found in the sympathectomized group 3 months after sympathectomy. Although sympathetic denervation occurred in the sacrococcygeal region and hind feet skin 2 weeks after lumbar sympathectomy, the skin functions recovered gradually over 7 weeks to 3 months. In conclusion, sympathetic functional recovery may account for the recurrence of hyperhidrosis after sympathectomy and the normalization of sympathetic nerve trunks after incomplete injury. The recovery of sympathetic nerve function was slower in the limbs than in the torso after bilateral L 2-4 sympathectomy.

  13. Recovery of sympathetic nerve function after lumbar sympathectomy is slower in the hind limbs than in the torso

    Directory of Open Access Journals (Sweden)

    Zhi-fang Zheng

    2017-01-01

    Full Text Available Local sympathetic denervation by surgical sympathectomy is used in the treatment of lower limb ulcers and ischemia, but the restoration of cutaneous sympathetic nerve functions is less clear. This study aims to explore the recovery of cutaneous sympathetic functions after bilateral L2–4 sympathectomy. The skin temperature of the left feet, using a point monitoring thermometer, increased intraoperatively after sympathectomy. The cytoplasm of sympathetic neurons contained tyrosine hydroxylase and dopamine β-hydroxylase, visualized by immunofluorescence, indicated the accuracy of sympathectomy. Iodine starch test results suggested that the sweating function of the hind feet plantar skin decreased 2 and 7 weeks after lumbar sympathectomy but had recovered by 3 months. Immunofluorescence and western blot assay results revealed that norepinephrine and dopamine β-hydroxylase expression in the skin from the sacrococcygeal region and hind feet decreased in the sympathectomized group at 2 weeks. Transmission electron microscopy results showed that perinuclear space and axon demyelination in sympathetic cells in the L5 sympathetic trunks were found in the sympathectomized group 3 months after sympathectomy. Although sympathetic denervation occurred in the sacrococcygeal region and hind feet skin 2 weeks after lumbar sympathectomy, the skin functions recovered gradually over 7 weeks to 3 months. In conclusion, sympathetic functional recovery may account for the recurrence of hyperhidrosis after sympathectomy and the normalization of sympathetic nerve trunks after incomplete injury. The recovery of sympathetic nerve function was slower in the limbs than in the torso after bilateral L2–4 sympathectomy.

  14. POLYETHYLENEIMINE (PEI)-MEDIATED TRANSFECTION OF SYMPATHETIC NEURONS IN VITRO. (R826248)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. Sympathetic and parasympathetic regulation of rectal motility in rats.

    Science.gov (United States)

    Ridolfi, Timothy J; Tong, Wei-Dong; Takahashi, Toku; Kosinski, Lauren; Ludwig, Kirk A

    2009-11-01

    The colon and rectum are regulated by the autonomic nervous system (ANS). Abnormalities of the ANS are associated with diseases of the colon and rectum while its modulation is a putative mechanism for sacral nerve stimulation. The purpose of this study is to establish a rat model elucidating the role of the efferent ANS on rectal motility. Rectal motility following transection or stimulation of parasympathetic pelvic nerves (PN) or sympathetic hypogastric nerves (HGN) was measured with rectal strain gauge transducers and quantified as a motility index (MI). Colonic transit was measured 24 hours after transection by calculating the geometric center (GC) of distribution of (51)Cr Transection of PN and HGN decreased MI to 518 +/- 185 g*s (p < 0.05) and increased MI to 5,029 +/- 1,954 g*s (p < 0.05), respectively, compared to sham (975 +/- 243 g*s). Sectioning of PN and HGN decreased transit with GC = 4.9 +/- 0.2 (p < 0.05) and increased transit with GC = 8.1 +/- 0.7 (p < 0.02), respectively, compared to sham (GC = 5.8 +/- 0.3). Stimulation of PN and HGN increased MI to 831 +/- 157% (p < 0.01) and decreased MI to 251 +/- 24% (p < 0.05), respectively. Rectal motility is significantly altered by sectioning or stimulating either HGN or PN. This model may be useful in studying how sacral nerve stimulation exerts its effects and provide insight into the maladies of colonic motility.

  16. [Progressive hemifacial atrophy with sympathetic nerve dysfunction of central origin].

    Science.gov (United States)

    Tsuchiya, I; Sahashi, K; Ibi, T; Iwase, S; Mano, T

    1989-09-01

    A 37-year-old unmarried man was admitted because of gait disturbance and right hemifacial atrophy. Family history was unremarkable. He had an unconscious attack at age 13 and had writer's cramp since age 15. He was thin and lipodystrophic. In reviewing his portraits, hemifacial atrophy was considered to develop in his early teens and to be progressive since then. Pigmented gum, high arched palate, mild mental retardation, pseudo-Argyll Robertson's pupil, sexual impotence, amyotrophy of the left thigh and the right calf, and a limp due to bony abnormalities was detected. Serological tests for syphilis were negative. Bone X-rays disclosed coxa-deformance. Cerebrospinal fluid. EMG, EEG, muscle biopsy and brain CT were normal. Hearing was decreased to 20-35 dB bilaterally. Plasma norepinephrine levels were 450 pg/ml in the supine position and 539 pg/ml in standing. Plasma renin activity was 5.1-5.4 ng/ml/hr. Microneurography revealed highly accentuated muscle and skin sympathetic nerve activities. Hypothermia on the feet, reduced CVR-R and decreased mydriatic response to 5% cocaine instillation were present. Intravenous infusion of norepinephrine and intradermal injection of either acetylcholine or histamine revealed normal results. In the case, sympathicotonia due to dysfunction in the central nervous system is considered to be related to the pathogenesis of hemifacial atrophy.

  17. Reflex sympathetic dystrophy/complex regional pain syndrome, type 1

    Directory of Open Access Journals (Sweden)

    S.H. Botha

    2004-06-01

    Full Text Available Complex regional pain syndrome (CPRS, type 1 is a pain disorder that develops unpredictably and can follow a minor injury. A 12-year-old boy presented with severe pain in the feet and could not walk or stand weight bearing. Normal X-rays showed osteopenic changes and radiolucent lines, which appeared to be stress fractures. Three-phase bone scintigraphy showed no uptake in the left lower leg on the blood pool phase or on the immediate or delayed images. This indicated typical CPRS type 1 in children. The uptake in the right foot was increased and the stress fracture and other illness could not be differentiated. Computed tomography was done to exclude stress fractures. Only osteopenic changes in both calcaneus bones were found and there was no evidence of cortical stress fractures. Magnetic resonance images revealed oedema in the calcaneus and talus bones of both feet. The patient received epidural narcotic infusion with sympathetic blockage for 1 week combined with extensive physiotherapy. The blood pool phase of the bone scan became normal within 2 weeks, and increased uptake in both feet was noticed. The patient was followed up with MRI every 3 months and the bone marrow oedema disappeared after 6 months.

  18. Reflex sympathetic dystrophy: a retrospective epidemiological study of 168 patients.

    Science.gov (United States)

    Duman, Iltekin; Dincer, Umit; Taskaynatan, Mehmet Ali; Cakar, Engin; Tugcu, Ilknur; Dincer, Kemal

    2007-09-01

    This is a retrospective epidemiological study. The objective is to determine the epidemiological characteristics including the patient demographics, etiological factors, duration of symptoms, treatment modalities applied and clinical outcome of the treatment in reflex sympathetic dystrophy (RSD). Medical records of the 168 patients managed in two tertiary hospitals with the diagnosis of RSD that was made according to both IASP criteria and three-phase bone scan were reviewed. The upper limb was affected 1.5 times as commonly as the lower limb. Of the 168 cases, 10.7% were non-traumatic. In 89.3% of the patients, RSD developed after a traumatic inciting event with a predominance of fracture. In 75.6% of the patients, RSD developed due to job-related injuries. The percentage of successful clinical outcome was 72%. The percentage of the patients that did not respond to therapy was 28%. The management period is long and this causes higher therapeutic costs in addition to loss of productive effort. However, response to therapy is good. On the other hand, in approximately one third of the patients, RSD does not improve despite all therapeutic interventions. In addition to compensation costs, this potentially debilitating feature causes RSD to appear as a socioeconomic problem.

  19. Acceptance of the different denominations for reflex sympathetic dystrophy

    Science.gov (United States)

    Alvarez-Lario, B; Aretxabala-Alciba..., I; Alegre-Lopez, J; Alonso-Valdiviels..., J

    2001-01-01

    OBJECTIVE—To elucidate the real impact in the medical literature of the different denominations for reflex sympathetic dystrophy (RSD).
METHODS—A search was performed through the Medline database (WinSPIRS, SilverPlatter International, NS), from 1995 to 1999, including the following descriptors: RSD, complex regional pain syndrome (CRPS), CRPS type I, algodystrophy, Sudeck, shoulder-hand syndrome, transient osteoporosis, causalgia, and CRPS type II.
RESULTS—The descriptor RSD was detected in 576 references, algodystrophy in 54, transient osteoporosis in 42, CRPS type I in 24, Sudeck in 16, and shoulder-hand syndrome in 11. One hundred records were obtained for the descriptor causalgia and five for CRPS type II. The descriptor RSD was detected in the title of 262 references, algodystrophy in 29, transient osteoporosis in 29, CRPS type I in 15, Sudeck in 3, shoulder-hand syndrome in 5, causalgia in 17, and CRPS type II in 3 references.
CONCLUSIONS—The new CRPS terminology has not effectively replaced the old one. RSD and causalgia are the most used denominations.

 PMID:11114289

  20. Reflex sympathetic dystrophy--a complex regional pain syndrome.

    Science.gov (United States)

    Turner-Stokes, L

    2002-12-15

    Reflex sympathetic dystrophy (RSD) is a complex and poorly-understood condition characterized by: (a) pain and altered sensation; (b) motor disturbance and soft tissue change; (c) vasomotor and autonomic changes; and (d) psychosocial disturbance. Neurological symptoms typically do not conform to any particular pattern of nerve damage. Many different names have been ascribed to this condition and most recently the term 'complex regional pain syndrome' has been coined to emphasize the complex interaction of somatic, psychological and behavioural factors. Diagnostic criteria have been proposed by the International Association for the Study of Pain, but are still subject to debate. This review article describes the clinical features which may present as part of the condition, and the patho-physiology and pre-disposing factors so far identified. The evidence for effectiveness of different interventions is presented and a treatment approach outlined for inter-disciplinary management. While RSD is traditionally associated with pain in the extremities, the possibility is raised that the same process may underlie chronic pain syndromes affecting more central structures, such as testicular or pelvic pain.

  1. [Reflex sympathetic dystrophy secondary to piriformis syndrome: a case report].

    Science.gov (United States)

    Akçali, Didem; Taş, Ayça; Cizmeci, Pelin; Oktar, Suna; Zinnuroğlu, Murat; Arslan, Emre; Köseoğlu, Hüseyin; Babacan, Avni

    2009-04-01

    Piriformis syndrome is a rare cause of hip and foot pain which may be due to sciatic nerve irritation because of anatomic abnormalities of sciatic nerve and piriformis muscle or herniated disc, facet syndrome, trochanteric bursit, sacroiliac joint dysfunction, endometriosis and other conditions where sciatic nerve is irritated. There has been no reflex sympathetic dystrophy (RSD) case presented due to piriformis syndrome before. A sixty-two-year-old female patient had right foot and hip pain (VNS: 8), redness and swelling in the foot since 15 days. Her history revealed long walks and travelling 3 weeks ago and sitting on the foot for a long time for a couple of days. Physical examination revealed painful hip movement, positive straight leg rise. Erythema and hyperalgesia was present in dorsum of the right foot. Right foot dorsiflexion was weak and hyperesthesia was found in right L4-5 dermatome. Medical treatment and ultrasound treatment to piriformis muscle was not effective. The patient was injected 40 mg triamcinolon and local anesthetic in right piriformis muscle under floroscopy by diagnosis of piriformis syndrome, neuropathic pain and RSD. Pain and hyperalgesia resolved and motor weakness was better. During follow-up right foot redness resolved and pain decreased (VNS: 1). In this case report, there was vascular, muscle and skeletal signs supporting RSD, which shows us the therapoetic effect of diagnostic piriformis injection. The patient history, physical examination and diagnostic tests were evaluated by a multidisciplinary team which contributed to the treatment.

  2. High-resolution Observations of Sympathetic Filament Eruptions by NVST

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shangwei; Su, Yingna; Zhou, Tuanhui; Ji, Haisheng [Key Laboratory for Dark Matter and Space Science, Purple Mountain Observatory, CAS, Nanjing 210008 (China); Van Ballegooijen, Adriaan [5001 Riverwood Avenue, Sarasota, FL 34231 (United States); Sun, Xudong, E-mail: ynsu@pmo.ac.cn [W. W. Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305 (United States)

    2017-07-20

    We investigate two sympathetic filament eruptions observed by the New Vacuum Solar Telescope on 2015 October 15. The full picture of the eruptions is obtained from the corresponding Solar Dynamics Observatory ( SDO )/Atmospheric Imaging Assembly (AIA) observations. The two filaments start from active region NOAA 12434 in the north and end in one large quiescent filament channel in the south. The left filament erupts first, followed by the right filament eruption about 10 minutes later. Clear twist structure and rotating motion are observed in both filaments during the eruption. Both eruptions failed, since the filaments first rise up, then flow toward the south and merge into the southern large quiescent filament. We also observe repeated activations of mini filaments below the right filament after its eruption. Using magnetic field models constructed based on SDO /HMI magnetograms via the flux rope insertion method, we find that the left filament eruption is likely to be triggered by kink instability, while the weakening of overlying magnetic fields due to magnetic reconnection at an X-point between the two filament systems might play an important role in the onset of the right filament eruption.

  3. Blockade of the MEK/ERK pathway with a raf inhibitor prevents activation of pro-inflammatory mediators in cerebral arteries and reduction in cerebral blood flow after subarachnoid hemorrhage in a rat model

    DEFF Research Database (Denmark)

    Maddahi, Aida; Ansar, Saema; Chen, Qingwen

    2011-01-01

    /ERK (MEK)/extracellular signal-regulated kinase (ERK) pathway upstream with a specific raf inhibitor would prevent SAH-induced activation of the cerebrovascular inflammatory response. The raf inhibitor SB-386023-b was injected intracisternally in our rat model at 0, 6, or 12 hours after the SAH. After 48...... normalized CBF and prevented SAH-induced upregulation of MMPs, pro-inflammatory cytokines, and pERK1/2 proteins. These results suggested that inhibition of MEK/ERK signal transduction by a specific raf inhibitor administered up to 6 hours after SAH normalized the expression of pro-inflammatory mediators...

  4. Influences of Vestibular System on Sympathetic Nervous System. Implications for countermeasures.

    Science.gov (United States)

    Denise, Pr Pierre

    As gravity is a direct and permanent stress on body fluids, muscles and bones, it is not surpris-ing that weightlessness has important effects on cardiovascular and musculo-skeletal systems. However, these harmful effects do not totally result from the removal of the direct stress of gravity on these organs, but are also partially and indirectly mediated by the vestibular sys-tem. Besides its well known crucial role in spatial orientation and postural equilibrium, it is now clear that the vestibular system is also involved in the regulation of other important physi-ological systems: respiratory and cardiovascular systems, circadian regulation, food intake and even bone mineralization. The neuroanatomical substrate for these vestibular-mediated reg-ulations is still poorly defined, but there is much evidence that vestibular system has strong impacts not only on brainstem autonomic centers but on many hypothalamic nuclei as well. As autonomic nervous system controls almost all body organs, bringing into play the vestibular system by hypergravity or microgravity could virtually affects all major physiological func-tions. There is experimental evidence that weightlessness as well as vestibular lesion induce sympathetic activation thus participating in space related physiological alterations. The fact that some effects of weightlessness on biological systems are mediated by the vestibular system has an important implication for using artificial gravity as a countermeasure: artificial gravity should load not only bones and the cardiovascular system but the vestibular system as well. In short-arm centrifuges, the g load at the head level is low because the head is near the axis of rotation. If the vestibular system is involved in cardiovascular deconditioning and bone loss during weightlessness, it would be more effective to significantly stimulate it and thus it would be necessary to place the head off-axis. Moreover, as the otolithic organs are non longer stimu-lated in

  5. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    Science.gov (United States)

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  6. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart

    Directory of Open Access Journals (Sweden)

    James Winter

    2018-01-01

    Full Text Available Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS.Objective: To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s by which the effects of SNS are mediated.Methods and Results: Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (IKs, sufficient to abolish IKs-mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endoplasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca

  7. Investigating the Effects of Mass Media Exposure on the Uptake of Preventive Measures by Hong Kong Residents during the 2015 MERS Outbreak: The Mediating Role of Interpersonal Communication and the Perception of Concern.

    Science.gov (United States)

    Ludolph, Ramona; Schulz, Peter J; Chen, Ling

    2018-01-01

    In 2015, South Korea experienced the largest outbreak to date of the Middle East Respiratory Syndrome (MERS-CoV) outside the Middle East. Fears related to a potential spread of the disease led to an increased alert level as well as heightened media coverage in the neighboring Hong Kong. A cross-sectional survey (N = 533) among residents of Hong Kong was conducted to assess the relationships between the effects of outbreak-related mass media coverage, interpersonal communication, the perceived level of concern in one's close environment, and the uptake of preventive measures. A serial multiple mediator model finds that interpersonal communication and higher perceived concern indirectly influence the effects of media coverage on the engagement in preventive actions. These results expand previous research on the mediating role of interpersonal communication and support assumptions about a modified two-step flow of communication in the context of a public health emergency.

  8. The Aqueous Calyx Extract of Hibiscus sabdariffa Lowers Blood Pressure and Heart Rate via Sympathetic Nervous System Dependent Mechanisms.

    Science.gov (United States)

    Aliyu, B; Oyeniyi, Y J; Mojiminiyi, F B O; Isezuo, S A; Alada, A R A

    2014-12-29

    The antihypertensive effect of Hibiscus sabdariffa (HS) has been validated in animals and man. This study tested the hypothesis that its hypotensive effect may be sympathetically mediated. The cold pressor test (CPT) and handgrip exercise (HGE) were performed in 20 healthy subjects before and after the oral administration of 15mg/Kg HS. The blood pressure (BP) and heart rate (HR) responses were measured digitally. Mean arterial pressure (MAP; taken as representative BP) was calculated. Results are expressed as mean ±SEM. P<0.05 was considered significant. CPT without HS resulted in a significant rise in MAP and HR (111.1±2.1mmHg and 100.8±2.0/min) from the basal values (97.9±1.9mmHg and 87.8±2.1/min; P<0.0001 respectively). In the presence of HS, CPT-induced changes (ΔMAP=10.1±1.7mmHg; ΔHR= 8.4±1.0/min) were significantly reduced compared to its absence (ΔMAP= 13.2±1.2mmHg; ΔHR= 13.8±1.6/min; P<0.0001 respectively). The HGE done without HS also resulted in an increase in MAP and HR (116.3±2.1mmHg and 78.4±1.2/min) from the basal values (94.8±1.6mmHg and 76.1±1.0/min; p<0.0001 respectively). In the presence of HS the HGE-induced changes (ΔMAP= 11.5±1.0mmHg; ΔHR= 3.3±1.0/min) were significantly decreased compared to its absence (ΔMAP=21.4±1.2mmHg; ΔHR= 12.8±2.0/min; P<0.0001 respectively). The CPT and HGE -induced increases in BP and HR suggest Sympathetic nervous system activation. These increases were significantly dampened by HS suggesting, indirectly, that its hypotensive effect may be due to an attenuation of the discharge of the sympathetic nervous system.

  9. TNF-α receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats.

    Science.gov (United States)

    Yu, Yang; Wei, Shun-Guang; Weiss, Robert M; Felder, Robert B

    2017-10-01

    In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA or a scrambled shRNA lentiviral vector carrying green fluorescent protein, or vehicle. One week later, some rats were euthanized to confirm the accuracy of the SFO microinjections and the transfection potential of the lentiviral vector. Other rats underwent coronary artery ligation (CL) to induce HF or a sham operation. Four weeks after CL, vehicle- and scrambled shRNA-treated HF rats had significant increases in TNFR1 mRNA and protein, NF-κB activity, and mRNA for inflammatory mediators, RAS components and c-Fos protein in the SFO and downstream in the hypothalamic paraventricular nucleus, along with increased plasma norepinephrine levels and impaired cardiac function, compared with vehicle-treated sham-operated rats. In HF rats treated with TNFR1 shRNA, TNFR1 was reduced in the SFO but not paraventricular nucleus, and the central and peripheral manifestations of HF were ameliorated. In sham-operated rats treated with TNFR1 shRNA, TNFR1 expression was also reduced in the SFO but there were no other effects. These results suggest a key role for TNFR1 in the SFO in the pathophysiology of systolic HF. NEW & NOTEWORTHY Activation of TNF-α receptor 1 in the subfornical organ (SFO) contributes to sympathetic excitation in heart failure rats by increasing inflammation and renin-angiotensin system activity in the SFO and downstream in the hypothalamic

  10. Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

    Science.gov (United States)

    Ramchandra, Rohit; Hood, Sally G; May, Clive N

    2014-08-01

    Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

  11. Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

    Directory of Open Access Journals (Sweden)

    Luis I Angel-Chavez

    Full Text Available In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV. Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

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

    Directory of Open Access Journals (Sweden)

    Jihong Xing

    2016-11-01

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

  13. Altered Sympathetic-to-Immune Cell Signaling via β2-Adrenergic Receptors in Adjuvant Arthritis

    Directory of Open Access Journals (Sweden)

    Dianne Lorton

    2013-01-01

    Full Text Available Adjuvant-induced arthritic (AA differentially affects norepinephrine concentrations in immune organs, and in vivo β-adrenergic receptor (β-AR agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered β-AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined β2-AR expression in spleen and draining lymph nodes (DLNs for the arthritic limbs using radioligand binding and western blots and splenocyte β-AR-stimulated cAMP production using enzyme-linked immunoassay (EIA. During severe disease, β-AR agonists failed to induce splenocyte cAMP production, and β-AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte β2-AR phosphorylation (pβ2-AR by protein kinase A (pβ2-ARPKA decreased in severe disease, and pβ2-AR by G protein-coupled receptor kinases (pβ2-ARGRK increased in chronic disease. Conversely, in DLN cells, pβ2-ARPKA rose during severe disease, but fell during chronic disease, and pβ2-ARGRK increased during both disease stages. A similar pβ2-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund’s adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors are important for DLN pβ2-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in β2-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis.

  14. Altered Sympathetic-to-Immune Cell Signaling via β 2-Adrenergic Receptors in Adjuvant Arthritis

    Science.gov (United States)

    Bellinger, Denise L.; Schaller, Jill A.; Osredkar, Tracy

    2013-01-01

    Adjuvant-induced arthritic (AA) differentially affects norepinephrine concentrations in immune organs, and in vivo β-adrenergic receptor (β-AR) agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered β-AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined β 2-AR expression in spleen and draining lymph nodes (DLNs) for the arthritic limbs using radioligand binding and western blots and splenocyte β-AR-stimulated cAMP production using enzyme-linked immunoassay (EIA). During severe disease, β-AR agonists failed to induce splenocyte cAMP production, and β-AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte β 2-AR phosphorylation (pβ 2-AR) by protein kinase A (pβ 2-ARPKA) decreased in severe disease, and pβ 2-AR by G protein-coupled receptor kinases (pβ 2-ARGRK) increased in chronic disease. Conversely, in DLN cells, pβ 2-ARPKA rose during severe disease, but fell during chronic disease, and pβ 2-ARGRK increased during both disease stages. A similar pβ 2-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund's adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors) are important for DLN pβ 2-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in β 2-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis. PMID:24194774

  15. Magnitude of Morning Surge in Blood Pressure Is Associated with Sympathetic but Not Cardiac Baroreflex Sensitivity.

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    Johnson, Aaron W; Hissen, Sarah L; Macefield, Vaughan G; Brown, Rachael; Taylor, Chloe E

    2016-01-01

    The ability of the arterial baroreflex to regulate blood pressure may influence the magnitude of the morning surge in blood pressure (MSBP). The aim was to investigate the relationships between sympathetic and cardiac baroreflex sensitivity (BRS) and the morning surge. Twenty-four hour ambulatory blood pressure was recorded in 14 young individuals. The morning surge was defined via the pre-awakening method, which is calculated as the difference between mean blood pressure values 2 h before and 2 h after rising from sleep. The mean systolic morning surge, diastolic morning surge, and morning surge in mean arterial pressures were 15 ± 2, 13 ± 1, and 11 ± 1 mmHg, respectively. During the laboratory protocol, continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made over a 10-min period of rest. Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified using the sequence method. The mean values for sympathetic BRSinc, sympathetic BRStotal and cardiac BRS were -1.26 ± 0.26 bursts/100 hb/mmHg, -1.60 ± 0.37 AU/beat/mmHg, and 13.1 ± 1.5 ms/mmHg respectively. Significant relationships were identified between sympathetic BRSinc and the diastolic morning surge (r = 0.62, p = 0.02) and the morning surge in mean arterial pressure (r = 0.57, p = 0.03). Low sympathetic BRS was associated with a larger morning surge in mean arterial and diastolic blood pressure. Trends for relationships were identified between sympathetic BRStotal and the diastolic morning surge (r = 0.52, p = 0.066) and the morning surge in mean arterial pressure (r = 0.48, p = 0.095) but these did not reach significance. There were no significant relationships between cardiac BRS and the morning surge. These findings indicate that the ability of the baroreflex to buffer increases in blood pressure

  16. Anatomical variations of rami communicantes in the upper thoracic sympathetic trunk.

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    Cho, Hyun Min; Lee, Doo Yun; Sung, Sook Whan

    2005-02-01

    The aim of this study was to clearly delineate the anatomical variations of the communicating rami in the upper thoracic sympathetic nervous system and to help develop better surgical method for essential palmar hyperhidrosis. Anatomical dissections of the upper thoracic sympathetic chains with sympathetic ganglia and communicating rami have been carried out in 42 adult Korean cadavers (male 26, female 16). The rami communicantes were classified into three types (Normal: transverse or oblique rami connected to the intercostal nerve of the same level; AR: ascending rami connected to the higher level; DR: descending rami to the lower level) based on the anatomical relationship of the thoracic sympathetic ganglia to the intercostal nerves. Both sides of the upper thoracic sympathetic nervous system were compared in the same individual. The number of the communicating rami was recorded in 32 cadavers (64 sides). The distance from the rami communicantes to the sympathetic trunk was measured in 26 cadavers (52 sides). The incidence of AR (ascending rami) and DR (descending rami) arising from the second sympathetic ganglion was 53.6% (45/84), 46.4% (39/84). From the third thoracic sympathetic ganglion, the incidence of AR was 5.9% (5/84) and that of DR was 26.2% (22/84). And in the fourth thoracic sympathetic ganglion, the incidence of AR was 4.8% (4/84) and DR was 8.3% (7/84), respectively. When we compared anatomical structures of both sides among the 42 cadavers dissected, only 14.3% (6/42) had similar anatomy of the rami communicantes bilaterally. Among 32 cadavers (64 sides), the mean number of rami communicantes at the second thoracic sympathetic ganglion was 2.1/2.5 in the left and the right side. At the third and the fourth thoracic sympathetic ganglion, the mean number was 1.9/1.6 and 1.7/1.7 in each side. The mean distance from the thoracic sympathetic chain to the most distal communicating rami of the left and right side at the second intercostal nerve was 7

  17. Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

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    Yrsa Bergmann Sverrisdóttir

    Full Text Available BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m, (age 37+/-11 yrs, (BMI 24+/-3 kg/m(2 direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index, was within the normal range (1.9-3.3 and MSNA was as expected for age and gender (13-44 burst/minute. RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005. RH-PAT index and MSNA were reciprocally related to time (h/week spent on physical activity (p = 0.005 and p = 0.006 respectively and platelet concentration (PLT (p = 0.02 and p = 0.004 respectively. CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular

  18. Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

    Science.gov (United States)

    Sverrisdóttir, Yrsa Bergmann; Jansson, Linda Marie; Hägg, Ulrika; Gan, Li-Ming

    2010-02-17

    Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. In 10 healthy normotensive subjects (3 f/7 m), (age 37+/-11 yrs), (BMI 24+/-3 kg/m(2)) direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA) were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT) technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index), was within the normal range (1.9-3.3) and MSNA was as expected for age and gender (13-44 burst/minute). RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005). RH-PAT index and MSNA were reciprocally related to time (h/week) spent on physical activity (p = 0.005 and p = 0.006 respectively) and platelet concentration (PLT) (p = 0.02 and p = 0.004 respectively). Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular health.

  19. Anterior cervical discectomy and fusion to treat cervical spondylosis with sympathetic symptoms.

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    Hong, Liu; Kawaguchi, Yoshiharu

    2011-02-01

    Retrospective study. To investigate the clinical effectiveness of polytheretherketone (PEEK) cages-assisted anterior cervical discectomy and fusion (ACDF) to treat cervical spondylosis with sympathetic symptoms. The diagnosis and treatment of cervical spondylosis with sympathetic symptoms has remained controversial. To date, few reports have focused on the surgical efficacy of cervical spondylosis with sympathetic symptoms. Retrospective analysis was undertaken for 39 patients who were diagnosed as cervical spondylosis with sympathetic symptoms and underwent ACDF with PEEK cages. They were followed up for at least 1 year. The mean follow-up was 15.6 months. Radiographs obtained before surgery, after surgery, and at the final follow-up were assessed for quality of fusion. The sympathetic symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb, hypomnesia, and gastroenterologic discomfort were scored by 20-point system preoperatively, 2 months postoperatively, and at the final follow-up. The recovery rate and clinical satisfaction rate were also evaluated. Surgical complications were also assessed. Radiographs of the cervical spine at the last follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases. In 2 patients delayed union and bony fusion were achieved at 9 and 11 months. Pseudoarthrosis was found in 1 case but the patient had no symptoms. The sympathetic symptoms improved in all patients and the score was significantly improved after surgery. There was one patient who had cerebral spinal fluid leakage but he recovered 1 week after surgery. Two patients felt a mild swallowing discomfort, but it disappeared within 1 month after surgery. Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was cleared 2 days after surgery. Cervical spondylosis patients with sympathetic symptoms may be managed successfully with ACDF using PEEK cages. Successful clinical results regarding symptom improvement

  20. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

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    Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi; hide

    2002-01-01

    Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

  1. Differential effects of defibrillation on systemic and cardiac sympathetic activity

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    Bode, F; Wiegand, U; Raasch, W; Richardt, G; Potratz, J

    1998-01-01

    Objective—To assess the effect of defibrillation shocks on cardiac and circulating catecholamines.
Design—Prospective examination of myocardial catecholamine balance during dc shock by simultaneous determination of arterial and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were applied in 30 patients after initiation of ventricular fibrillation for a routine implantable cardioverter defibrillator test. Another 10 patients were externally cardioverted (50-360 J) for atrial fibrillation.
Main outcome measures—Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after the shock.
Results—After internal shock, arterial noradrenaline increased from a mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01), reflecting a shift from cardiac net release to net uptake. After external shock delivery, there was a similar increase in arterial noradrenaline, from 260 (112) to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01), outlasting the threefold rise following internal shock (p = 0.001). In both groups, a negative transmyocardial adrenaline gradient at baseline decreased further, indicating enhanced myocardial uptake. Cardiac lactate production occurred after ventricular fibrillation and internal shock, but not after external cardioversion, so the neurohumoral changes resulted from the defibrillation process and not from alterations in oxidative metabolism.
Conclusions—A dc shock induces marked systemic sympathoadrenal and sympathoneuronal activation, but attenuates cardiac sympathetic activity. This might promote the transient myocardial depression observed after electrical discharge to the heart.

 Keywords: defibrillation;  autonomic cardiac function;  catecholamines;  lactate

  2. Increased vascular sympathetic modulation in mice with Mas receptor deficiency

    Science.gov (United States)

    Rabello Casali, Karina; Ravizzoni Dartora, Daniela; Moura, Marina; Bertagnolli, Mariane; Bader, Michael; Haibara, Andrea; Alenina, Natalia; Irigoyen, Maria Claudia; Santos, Robson A

    2016-01-01

    Introduction: The angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1–7)/Mas axis could modulate the heart rate (HR) and blood pressure variabilities (BPV) which are important predictors of cardiovascular risk and provide information about the autonomic modulation of the cardiovascular system. Therefore we investigated the effect of Mas deficiency on autonomic modulation in wild type and Mas-knockout (KO) mice. Methods: Blood pressure was recorded at high sample rate (4000 Hz). Stationary sequences of 200–250 beats were randomly chosen. Frequency domain analysis of HR and BPV was performed with an autoregressive algorithm on the pulse interval sequences and on respective systolic sequences. Results: The KO group presented an increase of systolic arterial pressure (SAP; 127.26±11.20 vs 135.07±6.98 mmHg), BPV (3.54±1.54 vs 5.87±2.12 mmHg2), and low-frequency component of systolic BPV (0.12±0.11 vs 0.47±0.34 mmHg2). Conclusions: The deletion of Mas receptor is associated with an increase of SAP and with an increased BPV, indicating alterations in autonomic control. Increase of sympathetic vascular modulation in absence of Mas evidences the important role of Ang-(1–7)/Mas on cardiovascular regulation. Moreover, the absence of significant changes in HR and HRV can indicate an adaptation of autonomic cardiac balance. Our results suggest that the Ang-(1–7)/Mas axis seems more important in autonomic modulation of arterial pressure than HR. PMID:27080540

  3. A new organellar complex in rat sympathetic neurons.

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    Matt S Ramer

    Full Text Available Membranous compartments of neurons such as axons, dendrites and modified primary cilia are defining features of neuronal phenotype. This is unlike organelles deep to the plasma membrane, which are for the most part generic and not related directly to morphological, neurochemical or functional specializations. However, here we use multi-label immunohistochemistry combined with confocal and electron microscopy to identify a very large (approximately 6 microns in diameter, entirely intracellular neuronal organelle which occurs singly in a ubiquitous but neurochemically distinct and morphologically simple subset of sympathetic ganglion neurons. Although usually toroidal, it also occurs as twists or rods depending on its intracellular position: tori are most often perinuclear whereas rods are often found in axons. These 'loukoumasomes' (doughnut-like bodies bind a monoclonal antibody raised against beta-III-tubulin (SDL.3D10, although their inability to bind other beta-III-tubulin monoclonal antibodies indicate that the responsible antigen is not known. Position-morphology relationships within neurons and their expression of non-muscle heavy chain myosin suggest a dynamic structure. They associate with nematosomes, enigmatic nucleolus-like organelles present in many neural and non-neural tissues, which we now show to be composed of filamentous actin. Loukoumasomes also separately interact with mother centrioles forming the basal body of primary cilia. They express gamma tubulin, a microtubule nucleator which localizes to non-neuronal centrosomes, and cenexin, a mother centriole-associated protein required for ciliogenesis. These data reveal a hitherto undescribed organelle, and depict it as an intracellular transport machine, shuttling material between the primary cilium, the nematosome, and the axon.

  4. Abnormal Cardiovascular Sympathetic and Parasympathetic Responses to Physical and Emotional Stimuli in Depersonalization Disorder.

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    Andrew Paul Owens

    2015-03-01

    Full Text Available Depersonalization disorder (DPD is characterized by subjective unreality, disembodiment, emotional numbing and reduced psychogenic sympathoexcitation. 3 related experiments used physical and emotional challenges in 14 DPD participants and 16 controls to elucidate whether the cardiovascular sympathetic (SNS and parasympathetic (PNS nervous systems are implicated in DPD and if blunted DPD sympathoexcitation is peripherally or centrally mediated. Participants completed the Beck Anxiety Inventory (BAI, Dissociative Experience Scale (DES and Cambridge Depersonalization Scale (CDS. Study I recorded heart rate (HR and blood pressure (BP during 5mins supine baseline, 3mins handgrip (HG, 3mins cold pressor (CP and 5mins 60°head-up tilt (HUT. Study II recorded HR, BP and heart rate variability (HRV during 5mins HUT and unpleasant images. Study III examined HR and BP orienting responses (ORs to HUT and unpleasant, neutral and pleasant images. DPD BAI (p=0.0004, DES (p=.0002 and CDS (p=< 0.0001 scores were higher than controls. The DPD group produced diminished diastolic BP (DBP (p=0.045 increases to HG. Other indices were comparable between groups. DPD participants produced diminished systolic BP (SBP (p=0.003 and DBP (p=0.002 increases, but greater (p=0.004 HR increases to CP. In study II, DPD high frequency HRV (HF-HRV – indicating parasympathetic vagal activity - was reduced (p=0.029. In study III, DPD DBP was higher throughout the 5s duration of HUT/pseudorandom unpleasant image presentation (1s [p=0.002], 2s [p=0.033], 3s [p=0.001], 4s [p=0.009], 5s [p=0.029]. Study I’s BP pressor data supports previous findings of suppressed sympathoexcitatioin DPD. The greater HR increases to CP, decreased HF-HRV in study II, and increased DBP during unpleasant ORs in study III implicates the SNS and PNS in DPD pathophysiology. These studies suggest the cardiovascular autonomic dysregulation in DPD is likely to be centrally-mediated

  5. Change in sympathetic nerve firing pattern associated with dietary weight loss in the metabolic syndrome

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    Elisabeth Annie Lambert

    2011-08-01

    Full Text Available Sympathetic activation in subjects with the metabolic syndrome (MS plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the firing behavior of single-unit sympathetic nerve fibres. Fourteen subjects (57±2 years, 9 men, 5 females fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters and multi-unit and single unit muscle sympathetic nerve activity (MSNA, microneurography were assessed prior to and at the end of the diet. Patients’ weight dropped from 96±4 to 88±3 kg (P<0.001. This was associated with a decrease in systolic and diastolic blood pressure (-12 ±3 and -5±2 mmHg, P<0.05, and in heart rate (-7±2 bpm, P<0.01 and an improvement in all metabolic parameters (fasting glucose: -0.302.1±0.118 mmol/l, total cholesterol: -0.564±0.164 mmol/l, triglycerides: -0.414±0.137 mmol/l, P<0.05. Multi-unit MSNA decreased from 68±4 to 59±5 bursts per 100 heartbeats (P<0.05. Single-unit MSNA indicated that the firing rate of individual vasoconstrictor fibres decreased from 59±10 to 32±4 spikes per 100 heart beats (P<0.05. The probability of firing decreased from 34±5 to 23±3 % of heartbeats (P<0.05, and the incidence of multiple firing decreased from 14±4 to 6±1 % of heartbeats (P<0.05. Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57±0.69 to 9.57±1.20 msec.mmHg-1; sympathetic slope: -3.86±0.34 to -5.05±0.47 bursts per 100 heartbeats.mmHg-1 P<0.05 for both. Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the firing pattern of

  6. Control of ketogenesis in the perfused rat liver by the sympathetic innervation.

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    Beuers, U; Beckh, K; Jungermann, K

    1986-07-01

    The regulation of ketogenesis by the hepatic nerves was investigated in the rat liver perfused in situ. Electrical stimulation of the hepatic nerves around the portal vein and the hepatic artery caused a reduction of basal ketogenesis owing to a decrease in acetoacetate release to 30% with essentially no change in 3-hydroxybutyrate release. At the same time, as observed before [Hartmann et al. (1982) Eur. J. Biochem. 123, 521-526], nerve stimulation increased glucose output, shifted lactate uptake to output and decreased perfusion flow. Ketogenesis from oleate, which enters the mitochondria via the carnitine system, was also lowered after nerve stimulation owing to a decrease of acetoacetate release to 30% with no alteration in 3-hydroxybutyrate release. Ketogenesis from octanoate, which enters the mitochondria independently of the carnitine system, was decreased after nerve stimulation as a result of a drastic decrease of acetoacetate output to 15% and a less pronounced decrease of 3-hydroxybutyrate release to 65%. Noradrenaline mimicked the metabolic nerve effects on ketogenesis only at the highly unphysiological concentration of 0.1 microM under basal conditions and in the presence of oleate as well as partly in the presence of octanoate. It was essentially not effective at a concentration of 0.01 microM, which might be reached in the sinusoids owing to overflow from the hepatic vasculature. Sodium nitroprusside prevented the hemodynamic changes after nerve stimulation; it did not affect the nerve-dependent reduction of ketogenesis under basal conditions and in the presence of oleate, yet it diminished the nerve effect on octanoate-dependent ketogenesis. Phentolamine clearly reduced the metabolic and hemodynamic nerve effects, while propranolol was without effect. The present data suggest that hepatic ketogenesis was inhibited by stimulation of alpha-sympathetic liver nerves directly rather than indirectly via hemodynamic changes or noradrenaline overflow from

  7. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

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    Yumie Morimoto-Kobayashi

    Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

  8. Effects of renal sympathetic denervation on post-myocardial infarction cardiac remodeling in rats.

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    Jialu Hu

    Full Text Available OBJECTIVE: To investigate the therapeutic effects of renal denervation (RD on post- myocardial infarction (MI cardiac remodeling in rats, the most optimal time for intervention and the sustainability of these effects. METHODS: One hundred SPF male Wistar rats were randomly assigned to N group (Normal, n=10, MI group(MI, n=20,RD group (RD, n=10, RD3+MI (MI three days after RD, n=20, MI1+RD (RD one day after MI, n=20, MI7+RD (RD seven days after MI, n=20. MI was produced through thoracotomic ligation of the anterior descending artery. RD was performed through laparotomic stripping of the renal arteriovenous adventitial sympathetic nerve. Left ventricular function, hemodynamics, plasma BNP, urine volume, urine sodium excretion and other indicators were measured four weeks after MI. RESULTS: (1 The left ventricular function of the MI group significantly declined (EF<40%, plasma BNP was elevated, urine output was significantly reduced, and 24-hour urine sodium excretion was significantly reduced. (2 Denervation can be achieved by surgically stripping the arteriovenous adventitia, approximately 3 mm from the abdominal aorta. (3 In rats with RD3+MI, MI1+RD and MI7+RD, compared with MI rats respectively, the LVEF was significantly improved (75 ± 8.4%,69 ± 3.8%,73 ± 5.5%, hemodynamic indicators were significantly improved, plasma BNP was significantly decreased, and the urine output was significantly increased (21.3 ± 5 ml,23.8 ± 5.4 ml,25.2 ± 8.7 ml. However, the urinary sodium excretion also increased but without significant difference. CONCLUSIONS: RD has preventive and therapeutic effects on post-MI cardiac remodeling.These effects can be sustained for at least four weeks, but there were no significant differences between denervation procedures performed at different times in the course of illness. Cardiac function, hemodynamics, urine volume and urine sodium excretion in normal rats were not affected by RD.

  9. Renal denervation in male rats with heart failure improves ventricular sympathetic nerve innervation and function.

    Science.gov (United States)

    Pinkham, Maximilian I; Loftus, Michael T; Amirapu, Satya; Guild, Sarah-Jane; Quill, Gina; Woodward, William R; Habecker, Beth A; Barrett, Carolyn J

    2017-03-01

    Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart. Copyright © 2017 the American Physiological Society.

  10. Changes in the Skin Conductance Monitor as an End Point for Sympathetic Nerve Blocks.

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    Gungor, Semih; Rana, Bhumika; Fields, Kara; Bae, James J; Mount, Lauren; Buschiazzo, Valeria; Storm, Hanne

    2017-11-01

    There is a lack of objective methods for determining the achievement of sympathetic block. This study validates the skin conductance monitor (SCM) as an end point indicator of successful sympathetic blockade as compared with traditional monitors. This interventional study included 13 patients undergoing 25 lumbar sympathetic blocks to compare time to indication of successful blockade between the SCM indices and traditional measures, clinically visible hyperemia, clinically visible engorgement of veins, subjective skin temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography, within a 30-minute observation period. Differences in the SCM indices were studied pre- and postblock to validate the SCM. SCM showed substantially greater odds of indicating achievement of sympathetic block in the next moment (i.e., hazard rate) compared with all traditional measures (clinically visible hyperemia, clinically visible engorgement of veins, subjective temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography; P ≤ 0.011). SCM indicated successful block for all (100%) procedures, while the traditional measures failed to indicate successful blocks in 16-84% of procedures. The SCM indices were significantly higher in preblock compared with postblock measurements (P SCM is a more reliable and rapid response indicator of a successful sympathetic blockade when compared with traditional monitors. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  11. Alterations of sympathetic nerve fibers in avascular necrosis of femoral head.

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    Li, Deqiang; Liu, Peilai; Zhang, Yuankai; Li, Ming

    2015-01-01

    Avascular necrosis of the femoral head (ANFH) was mainly due to alterations of bone vascularity. And noradrenaline (NA), as the neurotransmitter of the sympathetic nervous system (SNS), leads to the vasoconstriction by activating its α-Receptor. This study was to explore the nerve fiber density of the femoral head in the rabbit model of ANFH. Twenty New Zealand white rabbits were used in this study. The rabbit model of ANFH was established by the injection of methylprednisolone acetate. The nerve fiber density and distribution in the femoral head was determined using an Olympus BH2 microscope. Significant fewer sympathetic nerve fibers was found in the ANFH intertrochanteric bone samples (P = 0.036) with osteonecrosis. The number of sympathetic nerve fibers was compared between the two groups. And less sympathetic nerve fibers were found in later stage ANFH samples in comparison with those of early stages. ANFH might be preceded by an inflammatory reaction, and an inflammatory response might lead to arthritic changes in tissue samples, which in turn reduces the number of sympathetic nerve fibers.

  12. Identification of human sympathetic neurovascular control using multivariate wavelet decomposition analysis.

    Science.gov (United States)

    Saleem, Saqib; Teal, Paul D; Kleijn, W Bastiaan; Ainslie, Philip N; Tzeng, Yu-Chieh

    2016-09-01

    The dynamic regulation of cerebral blood flow (CBF) is thought to involve myogenic and chemoreflex mechanisms, but the extent to which the sympathetic nervous system also plays a role remains debated. Here we sought to identify the role of human sympathetic neurovascular control by examining cerebral pressure-flow relations using linear transfer function analysis and multivariate wavelet decomposition analysis that explicitly accounts for the confounding effects of dynamic end-tidal Pco2 (PetCO2 ) fluctuations. In 18 healthy participants randomly assigned to the α1-adrenergic blockade group (n = 9; oral Prazosin, 0.05 mg/kg) or the placebo group (n = 9), we recorded blood pressure, middle cerebral blood flow velocity, and breath-to-breath PetCO2 Analyses showed that the placebo administration did not alter wavelet phase synchronization index (PSI) values, whereas sympathetic blockade increased PSI for frequency components ≤0.03 Hz. Additionally, three-way interaction effects were found for PSI change scores, indicating that the treatment response varied as a function of frequency and whether PSI values were PetCO2 corrected. In contrast, sympathetic blockade did not affect any linear transfer function parameters. These data show that very-low-frequency CBF dynamics have a composite origin involving, not only nonlinear and nonstationary interactions between BP and PetCO2 , but also frequency-dependent interplay with the sympathetic nervous system. Copyright © 2016 the American Physiological Society.

  13. Neural correlates of fear-induced sympathetic response associated with the peripheral temperature change rate.

    Science.gov (United States)

    Yoshihara, Kazufumi; Tanabe, Hiroki C; Kawamichi, Hiroaki; Koike, Takahiko; Yamazaki, Mika; Sudo, Nobuyuki; Sadato, Norihiro

    2016-07-01

    Activation of the sympathetic nervous system is essential for coping with environmental stressors such as fearful stimuli. Recent human imaging studies demonstrated that activity in some cortical regions, such as the anterior cingulate cortex (ACC) and anterior insula cortex (aIC), is related to sympathetic activity. However, little is known about the functional brain connectivity related to sympathetic response to fearful stimuli. The participants were 32 healthy, right-handed volunteers. Functional magnetic resonance imaging (fMRI) was used to examine brain activity when watching horror and control movies. Fingertip temperature was taken during the scanning as a measure of sympathetic response. The movies were watched a second time, and the degree of fear (9-point Likert-type scale) was evaluated every three seconds. The brain activity of the ACC, bilateral aIC, and bilateral anterior prefrontal cortex (aPFC) was correlated with the change rate of fingertip temperature, with or without fearful stimuli. Functional connectivity analysis revealed significantly greater positive functional connectivity between the amygdala and the ACC and between the amygdala and the aIC when watching the horror movie than when watching the control movie. Whole-brain psycho-physiological interaction (PPI) analysis revealed that the functional connectivity between the left amygdala and the ACC was modulated according to the fear rating. Our results indicate that the increased functional connectivity between the left amygdala and the ACC represents a sympathetic response to fearful stimuli. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.

    Science.gov (United States)

    Mousa, Shaaban A; Shaqura, Mohammed; Brendl, Ute; Al-Khrasani, Mahmoud; Fürst, Susanna; Schäfer, Michael

    2010-11-01

    Endogenous opioids are known to be released within certain brain areas following stressful stimuli. Recently, it was shown that also leukocytes are a potential source of endogenously released opioid peptides following stress. They activate sensory neuron opioid receptors and result in the inhibition of local inflammatory pain. An important prerequisite for the recruitment of such leukocytes is the expression of intracellular adhesion molecule-1 (ICAM-1) in blood vessels of inflamed tissue. Here, we investigated the contribution of peripheral sensory and/or sympathetic nerves to the enhanced expression of ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes to promote the inhibition of inflammatory pain. Selective degeneration of either peripheral sensory or sympathetic nerve fibers by their respective neurotoxins, capsaicin or 6-hydroxydopamime, significantly reduced the subcutaneous immigration of β-endorphin- (END-) and met-enkephalin- (ENK-)-containing polymorphonuclear leukocytes (PMN) (in the early phase) and mononuclear cells (in the late phase) during painful Freund's complete adjuvant (FCA) rat hind paw inflammation. In contrast, this treatment did not alter the percentage of opioid peptide-containing leukocytes in the circulation. Calcitonin gene-related peptide- (CGRP-) and tyrosine hydroxylase- (TH-) immunoreactive (IR) nerve fibers were in close contact to ICAM-1 IR blood vessels within inflamed subcutaneous tissue. The selective degeneration of sensory or sympathetic nerve fibers attenuated the enhanced expression of vascular endothelial ICAM-1 after intraplantar (i.pl.) FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results suggest that, during localized inflammatory pain, peripheral sensory and sympathetic nerve fibers augment the expression of vascular endothelial ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes which consequently

  15. Sympathetic nerve activity and whole body heat stress in humans.

    Science.gov (United States)

    Low, David A; Keller, David M; Wingo, Jonathan E; Brothers, R Matthew; Crandall, Craig G

    2011-11-01

    We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ∼0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress. Thirteen subjects, dressed in a water-perfused suit, underwent at least one passive heat stress that increased internal temperature ∼1.3°C, while either MSNA (n = 8) or SSNA (n = 8) was continuously recorded. Heat stress significantly increased mean skin temperature (Δ∼5°C, P heat stress (Δ core temperature 0.63 ± 0.01°C) when expressed as burst frequency (26 ± 14 to 45 ± 16 bursts/min, P = 0.001), burst incidence (39 ± 13 to 48 ± 14 bursts/100 cardiac cyles, P = 0.03), or total activity (317 ± 170 to 489 ± 150 units/min, P = 0.02) and continued to increase until the end of heat stress (burst frequency: 61 ± 15 bursts/min, P = 0.01; burst incidence: 56 ± 11 bursts/100 cardiac cyles, P = 0.04; total activity: 648 ± 158 units/min, P = 0.01) relative to the mid-heating stage. Similarly, SSNA (total activity) increased midway through the heat stress (normothermia; 1,486 ± 472 to mid heat stress 6,467 ± 5,256 units/min, P = 0.03) and continued to increase until the end of heat stress (11,217 ± 6,684 units/min, P = 0.002 vs. mid-heat stress). These results indicate that both MSNA and SSNA continue to increase as internal temperature is elevated above previously reported values.

  16. Initiation of unconfined gas detonations in hydrocarbon-air mixtures by a sympathetic mechanism

    International Nuclear Information System (INIS)

    Bull, D.C.; Elsworth, J.E.

    1981-01-01

    The considered investigation is concerned with the study of the factors which influence detonation propagation in a gas of heterogeneous composition. The conducted experiments assess the ability of a blast wave, emerging from a donor gas detonation and crossing an air gap, to initiate detonation in a second, similar, acceptor gas mixture. Stoichiometric mixtures of both ethylene-air and propane-air are found to exhibit 'sympathetic' gas detonation only across small air gaps. Conditions critical to sympathetic gas detonation agree with predictions of a simple theory taking account of the net shock decay occurring across two acoustic interfaces bounded by an air gap. Sympathetic detonation occurs only if the strength of the shock upon entering the acceptor exceeds a threshold value for the particular gas mixture. Reinitiation of detonation is not satisfactorily explained by planar blast wave decay and autoignition considerations

  17. Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin

    Directory of Open Access Journals (Sweden)

    Theofilos M. Kolettis, MD, PhD

    2017-04-01

    Full Text Available We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ETB-deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ETB-deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.

  18. Mediational effects of self-efficacy dimensions in the relationship between knowledge of dengue and dengue preventive behaviour with respect to control of dengue outbreaks: a structural equation model of a cross-sectional survey.

    Science.gov (United States)

    Isa, Affendi; Loke, Yoon K; Smith, Jane R; Papageorgiou, Alexia; Hunter, Paul R

    2013-01-01

    Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2) = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

  19. Mediational effects of self-efficacy dimensions in the relationship between knowledge of dengue and dengue preventive behaviour with respect to control of dengue outbreaks: a structural equation model of a cross-sectional survey.

    Directory of Open Access Journals (Sweden)

    Affendi Isa

    Full Text Available Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour.We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963. Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

  20. Mediational Effects of Self-Efficacy Dimensions in the Relationship between Knowledge of Dengue and Dengue Preventive Behaviour with Respect to Control of Dengue Outbreaks: A Structural Equation Model of a Cross-Sectional Survey

    Science.gov (United States)

    Isa, Affendi; Loke, Yoon K.; Smith, Jane R.; Papageorgiou, Alexia; Hunter, Paul R.

    2013-01-01

    Background Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. Methods and Findings We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. Conclusions To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy. PMID:24086777

  1. [Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats].

    Science.gov (United States)

    Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Dong, Tao; Zhang, Guo-Xing

    2015-06-25

    The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P blood pressure induced by foot shock. Levels of TBARS, renin and AngII in plasma were increased significantly in foot shock group compared with that of control group (P oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.

  2. Differentiated baroreflex modulation of sympathetic nerve activity during deep brain stimulation in humans.

    Science.gov (United States)

    Sverrisdóttir, Yrsa B; Green, Alexander L; Aziz, Tipu Z; Bahuri, Nor Faizal A; Hyam, Jonathan; Basnayake, Shanika D; Paterson, David J

    2014-05-01

    Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.

  3. The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction

    Science.gov (United States)

    Floras, John S.; Ponikowski, Piotr

    2015-01-01

    Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. PMID:25975657

  4. Role of myocardial hypertrophy in trophic stimulation of indices of sympathetic cardiac innervation.

    Science.gov (United States)

    Lindpaintner, K; Lund, D D; Schmid, P G

    1987-01-01

    Indices of cardiac sympathetic innervation have commonly been found depressed in the failing, hypertrophied heart. In contrast, we have recently demonstrated that hemodynamically compensated, very gradually developing right ventricular hypertrophy is associated with an increase in sympathetic nervous markers. The present experiments were performed to corroborate these findings in a model of acutely induced right ventricular hypertrophy, and to further characterize changes in markers of autonomic innervation associated with cardiac hypertrophy. Male guinea pigs underwent either pulmonary artery banding (P) with an acutely constricting ligature, or bilateral stellate ganglionectomy (S), or both (PS). Appropriate sham procedures were performed in animals subjected to only one intervention; controls (C) underwent sham-S and sham-P. Groups of animals were sacrificed at 10 and 20 days after surgery. Cardiac tissues were weighed and subsequently analyzed for activities of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), two enzymes catalyzing the biosynthesis of catecholamines (CAs), and of choline acetyltransferase (CAT), a marker of parasympathetic activity, as well as for norepinephrine (NE). S resulted in profound depletions of cardiac NE of 88-92% and in significant decreases in the activities of DBH and TH. Marked right ventricular hypertrophy developed rapidly following P, and was not modified by S. Similar to our previous results, acute right ventricular hypertrophy was associated with moderate increases (10-20%) of sympathetic markers; following S, these increases (of presumably residual sympathetic innervation) were greatly enhanced, amounting to 171% and 105% for NE at 10 and 20 days, respectively. In contrast, sympathetic markers in the left ventricle of stellatectomized animals were not affected by P. Activity of CAT remained unaltered by the experimental interventions. Our experiments indicate that increases in markers of sympathetic

  5. Sympathetic reflex dystrophy with hypofixation of technetium 99 m pyrophosphates on bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Doury, P.; Pattin, S. (Hopital d' Instruction des Armees Begin, 94 - Saint-Mande (France)); Granier, R.; Metges, P.J. (Hopital d' Instruction des Armees du Val-de-Grace, 75 - Paris (France))

    1981-09-01

    A patient with sympathetic reflex dystrophy following injury to the right foot presented fairly typical clinical and radiological signs, though the hot phase was particularly short. Bone scan with technetium 99 m pyrophosphates demonstrated hypofixation, which, though extremely rare, has been previously reported in the published literature. The fact that isotopic bone hypofixation can occur during sympathetic reflex dystrophy should be recognised, as far from constituting an argument against the early diagnosis of this affection, it should enable the organic nature of the disorder to be confirmed, and assist the physician in making an early diagnosis.

  6. How a Simple Ankle Sprain Turned Into Neuropathic Pain: Complex Reflex Sympathetic Dystrophy Versus Erythromelalgia.

    Science.gov (United States)

    Lurati, Ann Regina

    2018-04-01

    A 36-year-old woman sustained a Grade 2 ankle sprain at work. Two days after the injury, the ankle and foot became red and she complained of "intense burning pain." First diagnosed with complex reflex sympathetic dystrophy, the employee was prescribed medications that provided some pain relief; a subsequent temporary nerve block provided additional relief. However, the symptoms returned and she was treated unsuccessfully with surgical sympathectomy. The employee was referred to a neurologist and diagnosed with primary erythromelalgia, a rare pain disorder that can be mistaken as complex reflex sympathetic dystrophy.

  7. Treatment of Reflex sympathetic dystrophy with Bee venom -Using Digital Infrared Thermographic Imaging-

    Directory of Open Access Journals (Sweden)

    Myung-jang Lim

    2006-12-01

    Full Text Available Objectives : The purpose of this case is to report the patient with Reflex sympathetic dystrophy, who is improved by Bee venom. Method : We treated the patient with Bee venom who was suffering from Reflex sympathetic dystrophy, using Digital Infrared Thermographic Imaging and Verbal Numerical Rating Scale(VNRS to evaluate the therapeutic effects. We compared the temperature of the patient body before and after treatment. Result and Conclusion : We found that Bee venom had excellent outcome to relieve pain, atrophy and ankle joint ROM, and that Bee venom also had clinical effect on hypothermia on the Digital Infrared Thermographic Imaging.

  8. Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

    DEFF Research Database (Denmark)

    Christensen, Tomas M; Simonsen, Lene; Holstein, Per E

    2011-01-01

    was the patients with acute Charcot foot (n=17) or chronic Charcot foot (n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients......: The patients with acute Charcot foot and first toe amputation had an increased blood flow in the affected foot and weakened but not absent venoarteriolar sympathetic axon reflex. In the other patient groups, a normal venoarteriolar sympathetic axon reflex in the feet was found. CONCLUSIONS: Peripheral...

  9. Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans

    DEFF Research Database (Denmark)

    Mitchell, D.A.; Lambert, G.; Secher, Niels H.

    2009-01-01

    A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A d...

  10. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    Jessica M. F. Hall

    2012-01-01

    Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  11. Leptin acts in the forebrain to differentially influence baroreflex control of lumbar, renal and splanchnic sympathetic nerve activity and heart rate

    Science.gov (United States)

    Li, Baoxin; Shi, Zhigang; Cassaglia, Priscila A.; Brooks, Virginia L.

    2013-01-01

    While leptin is known to increase sympathetic nerve activity (SNA), we tested the hypothesis that leptin also enhances baroreflex control of SNA and HR. Using α-chloralose anesthetized male rats, mean arterial pressure (MAP), HR, lumbar SNA (LSNA), splanchnic SNA (SSNA), and renal SNA (RSNA) were recorded before and for 2 hr after lateral cerebroventricular (LV) leptin or aCSF administration. Baroreflex function was assessed using a four parameter sigmoidal fit of HR and SNA responses to slow ramp (3-5 min) changes in MAP, induced by iv infusion of nitroprusside and phenylephrine. Leptin (3 μg) increased (Pbaroreflex maxima. Leptin also increased gain of baroreflex control of LSNA and RSNA, but not of SSNA or HR. The elevations in HR were eliminated by pretreatment with methscopalamine, to block parasympathetic nerve activity; however, after cardiac sympathetic blockade with atenolol, leptin still increased basal HR and MAP and the HR baroreflex maximum and minimum. Leptin (1.5 μg) also increased LSNA and enhanced LSNA baroreflex gain and maximum, but did not alter MAP, HR, or the HR baroreflex. LV aCSF had no effects. Finally, to test if leptin acts in the brainstem, leptin (3 μg) was infused into the 4th ventricle; however, no significant changes were observed. In conclusion, leptin acts in the forebrain to differentially influence baroreflex control of LSNA, RSNA, SSNA and HR, with the latter action mediated via suppression of parasympathetic nerve activity. PMID:23424232

  12. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats.

    Science.gov (United States)

    Perez, Christina M; Hazari, Mehdi S; Ledbetter, Allen D; Haykal-Coates, Najwa; Carll, Alex P; Cascio, Wayne E; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2015-01-01

    Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.).

  13. Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients: Prospective Case Series

    NARCIS (Netherlands)

    Brinkmann, J.; Heusser, K.; Schmidt, B.M.; Menne, J.; Klein, G.; Bauersachs, J.; Haller, H.; Sweep, F.C.; Diedrich, A.; Jordan, J.; Tank, J.

    2012-01-01

    Endovascular renal nerve ablation has been developed to treat resistant hypertension. In addition to lowering efferent renal sympathetic activation, the intervention may attenuate central sympathetic outflow through decreased renal afferent nerve traffic, as evidenced by a recent case report. We

  14. Entrainment pattern between sympathetic and phrenic nerve activities in the Sprague-Dawley rat: hypoxia-evoked sympathetic activity during expiration.

    Science.gov (United States)

    Dick, Thomas E; Hsieh, Y-H; Morrison, Shaun; Coles, Sharon K; Prabhakar, Nanduri

    2004-06-01

    Sympathetic and respiratory motor activities are entrained centrally. We hypothesize that this coupling may partially underlie changes in sympathetic activity evoked by hypoxia due to activity-dependent changes in the respiratory pattern. Specifically, we tested the hypothesis that sympathetic nerve activity (SNA) expresses a short-term potentiation in activity after hypoxia similar to that expressed in phrenic nerve activity (PNA). Adult male, Sprague-Dawley (Zivic Miller) rats (n = 19) were anesthetized (Equithesin), vagotomized, paralyzed, ventilated, and pneumothoracotomized. We recorded PNA and splanchnic SNA (sSNA) and generated cycle-triggered averages (CTAs) of rectified and integrated sSNA before, during, and after exposures to hypoxia (8% O(2) and 92% N(2) for 45 s). Inspiration (I) and expiration (E) were divided in half, and the average and area of integrated sSNA were calculated and compared at the following time points: before hypoxia, at the peak breathing frequency during hypoxia, immediately before the end of hypoxia, immediately after hypoxia, and 60 s after hypoxia. In our animal model, sSNA bursts consistently followed the I-E phase transition. With hypoxia, sSNA increased in both halves of E, but preferentially in the second rather than the first half of E, and decreased in I. After hypoxia, sSNA decreased abruptly, but the coefficient of variation in respiratory modulation of sSNA was significantly less than that at baseline. The hypoxic-evoked changes in sympathetic activity and respiratory pattern resulted in sSNA in the first half of E being correlated negatively to that in the second half of E (r = -0.65, P hypoxia, the variability in the entrainment pattern had returned to baseline. The preferential recruitment of late expiratory sSNA during hypoxia results from either activation by expiratory-modulated neurons or by non-modulated neurons whose excitatory drive is not gated during late E.

  15. Acute effects of angiotensin-converting enzyme inhibition versus angiotensin II receptor blockade on cardiac sympathetic activity in patients with heart failure.

    Science.gov (United States)

    Azevedo, Eduardo R; Mak, Susanna; Floras, John S; Parker, John D

    2017-10-01

    The beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (ANG II) receptor antagonists in patients with heart failure secondary to reduced ejection fraction (HFrEF) are felt to result from prevention of the adverse effects of ANG II on systemic afterload and renal homeostasis. However, ANG II can activate the sympathetic nervous system, and part of the beneficial effects of ACE inhibitors and ANG II antagonists may result from their ability to inhibit such activation. We examined the acute effects of the ACE inhibitor captopril (25 mg, n = 9) and the ANG II receptor antagonist losartan (50 mg, n = 10) on hemodynamics as well as total body and cardiac norepinephrine spillover in patients with chronic HFrEF. Hemodynamic and neurochemical measurements were made at baseline and at 1, 2, and 4 h after oral dosing. Administration of both drugs caused significant reductions in systemic arterial, cardiac filling, and pulmonary artery pressures ( P < 0.05 vs. baseline). There was no significant difference in the magnitude of those hemodynamic effects. Plasma concentrations of ANG II were significantly decreased by captopril and increased by losartan ( P < 0.05 vs. baseline for both). Total body sympathetic activity increased in response to both captopril and losartan ( P < 0.05 vs. baseline for both); however, there was no change in cardiac sympathetic activity in response to either drug. The results of the present study do not support the hypothesis that the acute inhibition of the renin-angiotensin system has sympathoinhibitory effects in patients with chronic HFrEF. Copyright © 2017 the American Physiological Society.

  16. Enlarged superior cervical sympathetic ganglion mimicking a metastatic lymph node in the retropharyngeal space: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Min; Kim, Jin Na; Kim, Se Hoon; Choi, Eun Chang [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    The superior cervical sympathetic ganglion, the largest and most cranial of the three cervical sympathetic ganglia, transfers sympathetic signals to specific targets on the head and neck. This ganglion is located just lateral to the retropharyngeal space along the medial margin of the carotid sheath. Located thus, an enlarged superior cervical sympathetic ganglion can mimic a metastatic lymph node in the retropharyngeal space of the suprahyoid neck in head and neck cancer patients. However, this is often disregarded by radiologists due to lack of interest in its anatomic location. We present a case of an enlarged superior cervical sympathetic ganglion mimicking a retropharyngeal metastatic lymph node in a 42-year-old man with oral tongue cancer.

  17. Why target early adolescents and parents in alcohol prevention? The mediating effects of self-control, rules and attitudes about alcohol use

    NARCIS (Netherlands)

    Koning, I.M.; Eijnden, R.J.J.M. van den; Engels, R.C.M.E.; Verdurmen, J.E.E.; Vollebergh, W.A.M.

    2011-01-01

    Aims To examine the effects of a parent and student intervention offered separately and simultaneously (PAS) on onset of weekly drinking via its putative mediators. Design A randomized trial with four conditions; (1) parent intervention, (2) student intervention, (3) combined parent-student

  18. The impact of information about the prevalence of aids-preventive behavior among men and women : The mediating role of social norms

    NARCIS (Netherlands)

    van den Eynden, R.J.J.M.; Buunk, Abraham (Bram); Bakker, A.B.; Siero, F.W.

    1998-01-01

    The present study was designed to examine the effect of information about the high prevalence of safe sex on condom use intention, and to investigate the possible mediating role of the perceived social norm of friends, and the perceived social norm of future sexual partners. Participants were

  19. The Effectiveness of the Life Skills Program IPSY for the Prevention of Adolescent Tobacco Use: The Mediating Role of Yielding to Peer Pressure

    Science.gov (United States)

    Weichold, Karina; Tomasik, Martin J.; Silbereisen, Rainer K.; Spaeth, Michael

    2016-01-01

    In this study, the effectiveness of a life skills program to impede tobacco use in early adolescence was scrutinized. The focus was on the mediating role of yielding to peer pressure. The universal school-based life skills program IPSY (Information + Psychosocial Competence = Protection) against adolescent substance use was implemented over 3…

  20. Effects of a combined parent-student alcohol prevention program on intermediate factors and adolescents’ drinking behavior: a sequential mediation model

    NARCIS (Netherlands)

    Koning, I.; Maric, M.; MacKinnon, D.; Vollebergh, W.A.M.

    2015-01-01

    OBJECTIVE: Previous work revealed that the combined parent-student alcohol prevention program (PAS) effectively postponed alcohol initiation through its hypothesized intermediate factors: increase in strict parental rule setting and adolescents' self-control (Koning, van den Eijnden, Verdurmen,

  1. Protective effect of sanguinarine on ultraviolet B-mediated damages in SKH-1 hairless mouse skin: implications for prevention of skin cancer.

    Science.gov (United States)

    Ahsan, Haseeb; Reagan-Shaw, Shannon; Eggert, David M; Tan, Thomas C; Afaq, Farrukh; Mukhtar, Hasan; Ahmad, Nihal

    2007-01-01

    Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280-320 nm), to human skin is the major cause of skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 micromol 0.3 mL(-1) ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer. However, further detailed studies are needed to support this suggestion.

  2. Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients.

    NARCIS (Netherlands)

    Courtar, D.A.; Spaanderman, M.E.A.; Aardenburg, R.; Janssen, B.J.; Peeters, L.L.

    2006-01-01

    BACKGROUND: Preeclampsia is associated with enhanced sympathetic activity as well as subnormal plasma volume. Meanwhile, in over 50% of these complicated pregnancies, the subnormal plasma volume has been found to persist for a prolonged period after pregnancy. The objective of this study is to test

  3. Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

    DEFF Research Database (Denmark)

    Neves, S R S; Machado, C R S; Pinto, A M T

    2006-01-01

    The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

  4. Angiotensin-dependent sympathetic vasoconstriction in SHR: The effect of captopril treatment in young animals

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2005-01-01

    Roč. 23, č. S2 (2005), S234-S234 ISSN 0263-6352. [European Meeting on Hypertension /15./. 17.06.2005-21.06.2005, Milan] R&D Projects: GA ČR(CZ) GA305/03/0769; GA MZd(CZ) NR7786 Keywords : angiotensin * sympathetic vasoconstriction * captopril * young animals Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. Acute electromyostimulation decreases muscle sympathetic nerve activity in patients with advanced chronic heart failure (EMSICA Study.

    Directory of Open Access Journals (Sweden)

    Marc Labrunée

    Full Text Available Muscle passive contraction of lower limb by neuromuscular electrostimulation (NMES is frequently used in chronic heart failure (CHF patients but no data are available concerning its action on sympathetic activity. However, Transcutaneous Electrical Nerve Stimulation (TENS is able to improve baroreflex in CHF. The primary aim of the present study was to investigate the acute effect of TENS and NMES compared to Sham stimulation on sympathetic overactivity as assessed by Muscle Sympathetic Nerve Activity (MSNA.We performed a serie of two parallel, randomized, double blinded and sham controlled protocols in twenty-two CHF patients in New York Heart Association (NYHA Class III. Half of them performed stimulation by TENS, and the others tested NMES.Compare to Sham stimulation, both TENS and NMES are able to reduce MSNA (63.5 ± 3.5 vs 69.7 ± 3.1 bursts / min, p < 0.01 after TENS and 51.6 ± 3.3 vs 56.7 ± 3.3 bursts / min, p < 0, 01 after NMES. No variation of blood pressure, heart rate or respiratory parameters was observed after stimulation.The results suggest that sensory stimulation of lower limbs by electrical device, either TENS or NMES, could inhibit sympathetic outflow directed to legs in CHF patients. These properties could benefits CHF patients and pave the way for a new non-pharmacological approach of CHF.

  6. Sympathetic Nervous Regulation in Patients with Cirrhosis: Pathogenesis of Fluid Retention and Formation of Ascites

    Directory of Open Access Journals (Sweden)

    Jens H Henriksen

    1991-01-01

    also be present. The authors conclude that the sympathetic nervous system, in concert with other regulatory systems, plays an important role in sodium-water homeostasis and fluid retention, as well as in the systemic and hepatosplanchnic circulatory derangement seen in patients with cirrhosis.

  7. Sympathetic skin response in incomplete spinal cord injury with urinary incontinence

    Directory of Open Access Journals (Sweden)

    Reza Emad

    2013-01-01

    Full Text Available Objectives: Sympathetic skin response (SSR is a test for evaluation of the sympathetic sweat gland pathways, and it has been used to study the central sympathetic pathways in spinal cord injury (SCI. This study aimed to assess the autonomic pathways according to normal or abnormal SSR in urinary incontinence patients due to incomplete spinal cord injury. Materials and Methods: Suprapubic, palmar, and plantar SSR to the peripheral nerve electrical stimulation were recorded in 16 urinary incontinence patients with incomplete spinal cord injury at various neurological levels and in 30 healthy control subjects. Results: All the recordings of SSR from the incomplete SCI patients with urinary incontinence as compared with their counterparts in the control group showed significantly reduced amplitudes with more prominent reduction in the suprapubic area recording site (P value < 0.0004. SSR with significantly prolonged latencies were recorded from palm and plantar areas in response to suprapubic area and tibial N stimuli, respectively (P value < 0.02. In this study, a significantly higher stimulus intensity (P value < 0.01 was needed to elicit SSR in the cases compared with the control group. Conclusion: This study showed abnormal SSR in urinary incontinence patients due to incomplete SCI. In addition, for the first time we have described recording of abnormal SSR from the suprapubic area as another way to show bladder sympathetic system involvement.

  8. Scintigraphic evaluation of regional myocardial sympathetic activity in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Eno, Shin; Takeo, Eiichiro; Katsumoto, Masayuki; Sasaki, Satoshi; Fujii, Hideaki; Kanazawa, Ikuo [Chugoku Rosai General Hospital, Kure, Hiroshima (Japan)

    1998-09-01

    Qualitative and quantitative analyses of sympathetic activity of heart and nervous sympathetic dysfunction in myocardium were investigated by using {sup 123}I-MIBG myocardial scintigraphy. Twelve normal persons (4 males, 8 females, mean age 61.3{+-}7.4) and 13 cases of dilated cardiomyopathy (11 males, 2 females, mean age 62.5{+-}14.2) were selected. Decrease of uptake rate to myocardium of I-MIBG (delayed image) and increase of washout rate were observed. Myocardial sympathetic hyperactivity was regarded as a main reason of these phenomena. Low uptake rate to myocardium of I-MIBG (delayed image) and high washout rate were observed in the whole left ventricle, and no difference of sympathetic activity according to locus of left ventricle was found. Correlation coefficient of left ventricular end-diastolic dimension with the washout rate of I-MIBG was 0.52 (p<0.05). It was suggested that washout rate may increase with progress of disease stage. (K.H.)

  9. Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

    DEFF Research Database (Denmark)

    Neves, S R S; Machado, C R S; Pinto, A M T

    2006-01-01

    The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions...

  10. Fostering College-Going Expectations of Immigrant Students through the Sympathetic Touch of School Leadership

    Science.gov (United States)

    Liou, Daniel D.

    2016-01-01

    This article intends to support the efforts of administrators, teachers, and community activists to center race, equity, and anti-deficit perspectives within the practice of school leadership. By drawing upon methods of critical race studies, and Du Bois's 1935 concept of the sympathetic touch, the author provides examples of anti-deficit…

  11. A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2017-01-01

    Full Text Available Accumulated evidence indicates that obesity-induced type 2 diabetes (T2D is associated with enhanced sympathetic activation. The present study was conducted to investigate the role for leptin-glutamate signaling within the hypothalamus in regulating sympathetic nerve activity. In anesthetized rats, microinjections of leptin (5 ng ~ 100 ng into the arcuate nucleus (ARCN and paraventricular nucleus (PVN induced increases in renal sympathetic nerve activity (RSNA, blood pressure (BP, and heart rate (HR. Prior microinjections of NMDA receptor antagonist AP5 (16 pmol into the ARCN or PVN reduced leptin-induced increases in RSNA, BP, and HR in both ARCN and PVN. Knockdown of a leptin receptor with siRNA inhibited NMDA-induced increases in RSNA, BP, and HR in the ARCN but not in the PVN. Confocal calcium imaging in the neuronal NG108 and astrocytic C6 cells demonstrated that preincubation with leptin induced an increase in intracellular calcium green fluorescence when the cells were challenged with glutamate. In high-fat diet and low-dose streptozotocin-induced T2D rats, we found that leptin receptor and NMDA NR1 receptor expressions in the ARCN and PVN were significantly increased. In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D.

  12. Standardization of I-123-meta-iodobenzylguanidine myocardial sympathetic activity imaging: phantom calibration and clinical applications

    NARCIS (Netherlands)

    Nakajima, Kenichi; Verschure, Derk O.; Okuda, Koichi; Verberne, Hein J.

    2017-01-01

    Purpose Myocardial sympathetic imaging with I-123-meta-iodobenzylguanidine (I-123-mIBG) has gained clinical momentum. Although the need for standardization of I-123-mIBG myocardial uptake has been recognized, the availability of practical clinical standardization approaches is limited. The need for

  13. Central sympathetic activation and arrhythmogenesis during acute myocardial infarction: modulating effects of endothelin-B receptors

    Directory of Open Access Journals (Sweden)

    Theofilos M Kolettis

    2015-02-01

    Full Text Available Sympathetic activation during acute myocardial infarction is an important arrhythmogenic mechanism, but the role of central autonomic inputs and their modulating factors remain unclear. Using the in vivo rat-model, we examined the effects of clonidine, a centrally-acting sympatholytic agent, in the presence or absence of myocardial endothelin-B (ETB receptors. We studied wild-type (n=20 and ETB-deficient rats (n=20 after permanent coronary ligation, with or without pretreatment with clonidine. Cardiac rhythm was continuously recorded for 24 hours by implantable telemetry devices, coupled by the assessment of autonomic and heart failure indices. Sympathetic activation and arrhythmogenesis were more prominent in ETB-deficient rats during the early phase post-ligation. Clonidine improved these outcomes throughout the observation period in ETB-deficient rats, but only during the delayed phase in wild-type rats. However, this benefit was counterbalanced by atrioventricular conduction abnormalities and by higher incidence of heart failure, the latter particularly evident in ETB-deficient rats. Myocardial ETB-receptors attenuate the arrhythmogenic effects of central sympathetic activation during acute myocardial infarction. ETB-receptor deficiency potentiates the sympatholytic effects of clonidine and aggravates heart failure. The interaction between endothelin and sympathetic responses during myocardial ischemia/infarction and its impact on arrhythmogenesis and left ventricular dysfunction merit further investigation.

  14. Enhanced sympathetic arousal in response to FMRI scanning correlates with task induced activations and deactivations.

    Directory of Open Access Journals (Sweden)

    Markus Muehlhan

    Full Text Available It has been repeatedly shown that functional magnetic resonance imaging (fMRI triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA, as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults.

  15. The Suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons

    NARCIS (Netherlands)

    Buijs, Ruud M.; la Fleur, Susanne E.; Wortel, Joke; van Heyningen, Caroline; Zuiddam, Laura; Mettenleiter, Thomas C.; Kalsbeek, Andries; Nagai, Katsuya; Niijima, Akira

    2003-01-01

    Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep-wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the

  16. Central Gi(2) proteins, sympathetic nervous system and blood pressure regulation

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef

    2016-01-01

    Roč. 216, č. 3 (2016), s. 258-259 ISSN 1748-1708 Institutional support: RVO:67985823 Keywords : inhibitory G proteins * sympathetic nervous system * central blood pressure control Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.867, year: 2016

  17. Cardiac sympathetic activity in hypertrophic cardiomyopathy and Tako-tsubo cardiomyopathy

    NARCIS (Netherlands)

    Verschure, Derk O.; van Eck-Smit, Berthe L. F.; Somsen, G. Aernout; Verberne, Hein J.

    2015-01-01

    (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy has been established as an important technique to evaluate cardiac sympathetic function and it has been shown to be of clinical value, especially for the assessment of prognosis, in many cardiac diseases. The majority of (123)I-mIBG

  18. Spinal Cord Injury-Induced Dysautonomia via Plasticity in Paravertebral Sympathetic Postganglionic

    Science.gov (United States)

    2015-10-01

    the dominant sympathetic control of vascular function in the trunk and upper extremities. Given their strategic nodal site in autonomic signaling to...across the motoneuron pool. Progress in brain research 143, 77-95 (2004). 16 Lujan, H. L., Janbaih, H. & DiCarlo, S. E. Dynamic interaction between the

  19. Cortisol and Children's Adjustment: The Moderating Role of Sympathetic Nervous System Activity

    Science.gov (United States)

    El-Sheikh, Mona; Erath, Stephen A.; Buckhalt, Joseph A.; Granger, Douglas A.; Mize, Jacquelyn

    2008-01-01

    We examined relations among cortisol, markers of sympathetic nervous system (SNS) activity (including salivary alpha-amylase and skin conductance level), and children's adjustment. We also tested the Bauer et al. ("Journal of Developmental and Behavioral Pediatrics," 23(2), 102-113, 2002) hypothesis that interactions between the SNS and cortisol…

  20. Dynamic scintigraphic study of the reflex sympathetic dystrophy syndrome and of osteonecrosis of the femoral condyle

    Energy Technology Data Exchange (ETDEWEB)

    Laurin, J.; Acquaviva, P.C.; Siles, P.C.; Kaphan, G.

    1985-01-01

    Bone scintigraphy associated with a dynamic study is being increasingly used in order to improve the specificity of the method. This dynamic study is performed with the injection of a bone seeker 99mTc-methylene diphosphonate. The method is found to be valuable for early identification of patients with suspected reflex sympathetic distrophy syndrome and with osteonecrosis of the femoral condyle.

  1. Lawsuit verdicts and settlements involving reflex sympathetic dystrophy and complex regional pain syndrome.

    Science.gov (United States)

    Crick, Brian C; Crick, John C

    2011-01-01

    Litigation involving Reflex Sympathetic Dystrophy (RSD) or Complex Regional Pain Syndrome (CRPS), because of its complexities, is often difficult to prove or defend. In our review of 56 verdicts and settlements in the state of Florida, in cases involving a diagnosis or misdiagnosis of RSD or CRPS, over half resulted in a substantial verdict or settlement for the plaintiff.

  2. [Polytopic and recurrent reflex sympathetic dystrophy in lower limbs in two siblings].

    Science.gov (United States)

    Bruscas Izu, C; Beltrán Auderá, C H; Jiménez Zorzo, F

    2004-04-01

    Reflex sympathetic dystrophy (RSD) has been related to a variety of inciting and predisposing factors. However, there are few reports of a familiar or genetic background in RSD. This paper describes two cases of RSD polytopic and recurrent in lower limbs of two brothers with similar HLA.

  3. The role of the pain psychologist, trigger point injections, reflex sympathetic dystrophy.

    Science.gov (United States)

    Fishman, Scott M

    2006-01-01

    This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are the role of the pain psychologist, trigger point injections, and reflex sympathetic dystrophy.

  4. Reflex sympathetic dystrophy syndrome associated with burns of the upper extremity

    Science.gov (United States)

    Balakrishnan, Chenicheri; Bradt, Lisa M; Rankin, David; Pane, Thomas A

    2004-01-01

    Reflex sympathetic dystrophy syndrome is an ill-defined symptom complex with clinical manifestations of excessive pain, joint stiffness and soft tissue changes. It rarely manifests following burns. Diagnosis is usually made from clinical symptoms and ganglion block. Early diagnosis and institution of conservative management is required to control symptoms and disability. PMID:24115872

  5. Predictors of Pain Relieving Response to Sympathetic Blockade in Complex Regional Pain Syndrome Type 1

    NARCIS (Netherlands)

    van Eijs, F.; Geurts, J.; van Kleef, M.; Faber, C.G.; Perez, R.S.G.M.; Kessels, A.G.; van Zundert, J.

    2012-01-01

    BACKGROUND:: Sympathetic blockade with local anesthetics is used frequently in the management of complex regional pain syndrome type 1(CRPS-1), with variable degrees of success in pain relief. The current study investigated which signs or symptoms of CRPS-1 could be predictive of outcome. The

  6. Dynamic scintigraphic study of the reflex sympathetic dystrophy syndrome and of osteonecrosis of the femoral condyle

    International Nuclear Information System (INIS)

    Laurin, J.; Acquaviva, P.C.; Siles, P.C.; Kaphan, G.

    1985-01-01

    Bone scintigraphy associated with a dynamic study is being increasingly used in order to improve the specificity of the method. This dynamic study is performed with the injection of a bone seeker 99mTc-methylene diphosphonate. The method is found to be valuable for early identification of patients with suspected reflex sympathetic distrophy syndrome and with osteonecrosis of the femoral condyle [fr

  7. Evidence for a local sympathetic venoarteriolar "reflex" in the dog hindleg

    DEFF Research Database (Denmark)

    Henriksen, O; Amtorp, O; Faris, I

    1983-01-01

    The study was performed in order to determine whether a local sympathetic venoarteriolar "reflex" is present in the dog hindleg. Femoral artery blood flow was measured by an electromagnetic flowmeter probe, and blood flow in the thigh muscle and subcutaneous tissue distally in the paw was measure...

  8. Sex Comparisons in Muscle Sympathetic Nerve Activity and Arterial Pressure Oscillations During Progressive Central Hypovolemia

    Science.gov (United States)

    2015-01-01

    Specifically, the ‘reserve’ for autonomic responses associated with blood pressure-sympathetic nerve activity (MSNA) coherence and vasoconstrictor reserves has...134. Convertino, V. A., C. A. Rickards, and K. L. Ryan. 2012. Autonomic mechanisms associated with heart rate and vasoconstrictor reserves. Clin. Auton

  9. Sympathetic activation by the cold pressor test does not increase the muscle force generation capacity.

    Science.gov (United States)

    Roatta, Silvestro; Farina, Dario

    2011-06-01

    A positive inotropic action by the sympathetic nervous system on skeletal muscles has been observed and investigated in animal and in vitro studies. This action provided a theoretical basis for the putative ergogenic action of catecholamines and adrenergic agonists, although there is no clear evidence of this effect in humans. The aim of this study was to investigate the occurrence of inotropic effects associated to physiological sympathetic activation in healthy subjects. The muscle force capacity was investigated in the tibialis anterior (n = 9 subjects) and in the soleus (n = 9) muscles electrically stimulated with single pulses and double pulses with variable interspike interval (4-1,000 ms) and short pulse trains (frequency: 5-14 Hz) before, during, and after sympathetic activation by the cold pressor test (CPT). CPT significantly decreased by 10.4 ± 7.2 and 10.6 ± 4.4% the force produced by single and double pulse stimulation, respectively, and produced smaller decreases in the force obtained by train stimulation in the tibialis anterior, while no significant changes were observed in either type of contraction in the soleus muscle. CPT failed to induce any increase in the force capacity of the investigated muscles. The prevalent decrease in force evidenced in this study supports the concept that the weakening sympathetic action on type I fiber, already shown to occur in humans, prevails over the putative potentiating action.

  10. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

    NARCIS (Netherlands)

    Kox, M.; Eijk, L.T.G.J. van; Zwaag, J.; Wildenberg, J. van den; Sweep, F.C.; Hoeven, J.G. van der; Pickkers, P.

    2014-01-01

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot

  11. Using a forehead reflectance pulse oximeter to detect changes in sympathetic tone.

    Science.gov (United States)

    Wendelken, Suzanne M; McGrath, Susan P; Akay, Metin; Blike, George T

    2004-01-01

    The extreme conditions of combat and multi-casualty rescue often make field triage difficult and put the medic or first responder at risk. In an effort to improve field triage, we have developed an automated remote triage system called ARTEMIS (automated remote triage and emergency management information system) for use in the battlefield or disaster zone. Common to field injuries is a sudden change in arterial pressure resulting from massive blood loss or shock. In effort to stabilize the arterial pressure, the sympathetic system is strongly activated and sympathetic tone is increased. This preliminary research seeks to empirically demonstrate that a forehead reflectance pulse oximeter is a viable sensor for detecting sudden changes in sympathetic tone. We performed the classic supine-standing experiment and collected the raw waveform, the photoplethysmogram (PPG), continuously using a forehead reflectance pulse oximeter. The resulting waveform was processed in Matlab using various spectral analysis techniques (FFT and AR). Our preliminary results show that a relative ratio analysis (low frequency power/high frequency power) for both the raw PPG signal and its derived pulse statistics (height, beat-to-beat interval) is a useful technique for detecting change in sympathetic tone resulting from positional change.

  12. Anatomic Variation of Rami Communicantes in the Upper Thoracic Sympathetic Chain: A Human Cadaveric Study.

    Science.gov (United States)

    Street, Elliot; Ashrafi, Mohammed; Greaves, Nicholas; Gouldsborough, Ingrid; Baguneid, Mohamed

    2016-07-01

    Hyperhidrosis is secondary to over activation of the sympathetic nervous system and surgical sympathectomy is the treatment of choice when other modalities have failed. This study investigated anatomic variation in the upper thoracic sympathetic chain and associated rami communicantes among cadaveric specimens. It considers the implications of these findings on surgical techniques to treat hyperhidrosis. The upper 4 thoracic sympathetic ganglia, intercostal nerves, and connecting rami were dissected, measured and mapped in 40 sides of 20 adult human cadavers. Ganglia location was recorded. The incidence, orientation, and distance travelled by rami communicantes was compared across different ganglionic levels and between sides. The percentage of ganglia located below their associated intercostal space was 6.25% with stellate ganglions present in 70% of specimens and Kuntz fibers noted in 40%. There was a stepwise reduction in incidence of rami from superior to inferior placed ganglia. The number of rami identified across all levels was significantly greater on the right (P = 0.03). The horizontal distance between the sympathetic chain and union of the rami on the intercostal nerves was significantly greater on the right across all levels (P = 0.04). There was substantial variation in the rami communicantes across the upper 4 ganglia and between right and left sides. Consideration of this variation should be given when planning surgical sympathectomy for hyperhidrosis particularly to avoid symptom recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

    Science.gov (United States)

    Moffitt, J. A.; Foley, C. M.; Schadt, J. C.; Laughlin, M. H.; Hasser, E. M.

    1998-01-01

    The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

  14. Sympathetic responses during saline infusion into the veins of an occluded limb.

    Science.gov (United States)

    Cui, Jian; McQuillan, Patrick; Moradkhan, Raman; Pagana, Charles; Sinoway, Lawrence I

    2009-07-15

    Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 +/- 1.2 bursts min(-1)), MSNA increased significantly during the saline infusion (22.5 +/- 2.6 bursts min(-1), P Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.

  15. Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity

    Science.gov (United States)

    El-Sheikh, Mona; Kouros, Chrystyna D.; Erath, Stephen; Cummings, E. Mark; Keller, Peggy; Staton, Lori

    2009-01-01

    Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS) activity were examined as moderators. PNS activity was indexed by respiratory sinus arrhythmia (RSA) and RSA reactivity (RSA-R) to lab…

  16. The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons

    NARCIS (Netherlands)

    K. Tsarovina (Konstantina); T. Reiff (Tobias); J. Stubbusch (Jutta); D. Kurek (Dorota); F.G. Grosveld (Frank); R. Parlato (Rosanna); G. Schütz (Günther); H. Rohrer (Hermann)

    2010-01-01

    textabstractThe transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional

  17. Adolescent sympathetic activity and salivary C-reactive protein: The effects of parental behavior.

    Science.gov (United States)

    Nelson, Benjamin W; Byrne, Michelle L; Simmons, Julian G; Whittle, Sarah; Schwartz, Orli S; Reynolds, Eric C; O'Brien-Simpson, Neil M; Sheeber, Lisa; Allen, Nicholas B

    2017-10-01

    This study utilized a novel multisystem approach to investigate the effect of observed parental behavior on the relationship between biological mechanisms associated with disease processes (i.e., autonomic physiology and immune response) among their adolescent children. Thirty-three adolescents (23 males), aged 11-13, and their parents participated in a laboratory session in which adolescents provided baseline measures of autonomic (sympathetic) activity, and adolescents and 1 parent participated in a laboratory based dyadic conflict resolution interaction task. This included 3 male parent/male adolescent dyads, 20 female parent/male adolescent dyads, 3 male parent/female adolescent dyads, and 7 female parent/female adolescent dyads. Approximately 3 years later, adolescents provided a salivary measure of C-Reactive Protein (sCRP) to index inflammation. Analyses revealed a positive association between sympathetic activity and sCRP, as well as a moderating role of positive parental behavior in this relationship, such that the association between sympathetic activity and sCRP was greater among adolescents whose parents displayed shorter duration of positive affect. Overall findings indicate parental behavior may influence the association between adolescent sympathetic activity and inflammatory processes. These findings have important implications for understanding the impact of psychosocial factors on biological mechanisms of disease. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Sympathetic neurotransmitters promote the process of recellularization in decellularized liver matrix via activating the IL-6/Stat3 pathway.

    Science.gov (United States)

    Wen, Xudong; Huan, Hongbo; Wang, Xiaojun; Chen, Xuejiao; Wu, Lili; Zhang, Yujun; Liu, Weihui; Bie, Ping; Xia, Feng

    2016-11-04

    Recellularized liver, as an approach for hepatic tissue engineering, is an effective alternative to orthotopic liver transplantation for end-stage hepatic failure. When compared with normal liver, recellularized liver has a disparity in hepatocyte viability and function, owing to the difficulty of fully simulating the microenvironment of liver. Although the sympathetic nervous system (SNS) is considered an important constituent of liver function, few studies have examined the effect of the SNS on hepatic tissue engineering. It is imperative to explore the regulation of the SNS on a tissue-like configuration to obtain an intact recellularized liver with better hepatic function. We have observed that various subtypes of adrenergic receptors (ARs) are expressed on the hepatocyte membrane. Salbutamol, an agonist of β2-AR, promoted cell proliferation, albumin secretion and urea synthesis in the recellularized liver. Cytokines were screened in isoprenaline/salbutamol-treated recellularized liver, and the expression of IL-6 was significantly increased. Isoprenaline or salbutamol especially promoted the expression of Stat 3 and phosphorylated Stat 3, contributing to the activation of IL-6/Stat 3 signalling in promoting hepatocyte proliferation and recellularized liver function. This study suggests that activation of β2-AR accelerated hepatocyte proliferation and improved recellularized liver function by mediating the IL-6/Stat 3 signalling pathway, indicating that nervous system regulation may be an essential component contributing to the complexity of recellularized liver in tissue engineering.

  19. Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans

    Science.gov (United States)

    Wilson, T. E.; Cui, J.; Crandall, C. G.

    2001-01-01

    1. Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2. In seven subjects mean arterial blood pressure was lowered (approximately 8 mmHg) and then raised (approximately 13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3. Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 +/- 3 to 92 +/- 4 beats x min(-1); P baroreflex function in these subjects. 4. Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5. These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals.

  20. Sympathetic modulation of muscle spindle afferent sensitivity to stretch in rabbit jaw closing muscles.

    Science.gov (United States)

    Roatta, S; Windhorst, U; Ljubisavljevic, M; Johansson, H; Passatore, M

    2002-04-01

    Previous reports showed that sympathetic stimulation affects the activity of muscle spindle afferents (MSAs). The aim of the present work is to study the characteristics of sympathetic modulation of MSA response to stretch: (i) on the dynamic and static components of the stretch response, and (ii) on group Ia and II MSAs to evaluate potentially different effects. In anaesthetised rabbits, the peripheral stump of the cervical sympathetic nerve (CSN) was stimulated at 10 impulses s(-1) for 45-90 s. The responses of single MSAs to trapezoidal displacement of the mandible were recorded from the mesencephalic trigeminal nucleus. The following characteristic parameters were determined from averaged trapezoidal responses: initial frequency (IF), peak frequency at the end of the ramp (PF), and static index (SI). From these, other parameters were derived: dynamic index (DI = PF - SI), dynamic difference (DD = PF - IF) and static difference (SD = SI - IF). The effects of CSN stimulation were also evaluated during changes in the state of intrafusal muscle fibre contraction induced by succinylcholine and curare. In a population of 124 MSAs, 106 units (85.4 %) were affected by sympathetic stimulation. In general, while changes in resting discharge varied among different units (Ia vs. II) and experimental conditions (curarised vs. non-curarised), ranging from enhancement to strong depression of firing, the amplitude of the response to muscle stretches consistently decreased. This was confirmed and detailed in a quantitative analysis performed on 49 muscle spindle afferents. In both the non-curarised (23 units) and curarised (26 units) condition, stimulation of the CSN reduced the response amplitude in terms of DD and SD, but hardly affected DI. The effects were equally present in both Ia and II units; they were shown to be independent from gamma drive and intrafusal muscle tone and not secondary to muscle hypoxia. Sympathetic action on the resting discharge (IF) was less

  1. Nonselective Blocking of the Sympathetic Nervous System Decreases Detrusor Overactivity in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Chang-Shin Park

    2012-04-01

    Full Text Available The involuntary dual control systems of the autonomic nervous system (ANS in the bladder of awake spontaneously hypertensive rats (SHRs were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO objectively as a core symptom of an overactive bladder. SHRs (n = 6 showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%. DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01, and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05. This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

  2. Morning blood pressure surge is associated with arterial stiffness and sympathetic baroreflex sensitivity in hypertensive seniors

    Science.gov (United States)

    Okada, Yoshiyuki; Galbreath, M. Melyn; Shibata, Shigeki; Jarvis, Sara S.; Bivens, Tiffany B.; Vongpatanasin, Wanpen; Levine, Benjamin D.

    2013-01-01

    Morning blood pressure (BP) surge is considered to be an independent risk factor for cardiovascular diseases. We tested the hypothesis that increased large-artery stiffness and impaired sympathetic baroreflex sensitivity (BRS) contribute to augmented morning surge in elderly hypertensive subjects. Morning surge was assessed as morning systolic BP averaged for 2 h just after waking up minus minimal sleeping systolic BP by using ambulatory BP monitoring (ABPM) in 40 untreated hypertensive [68 ± 1 (SE) yr] and 30 normotensive (68 ± 1 yr) subjects. Beat-by-beat finger BP and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and at 60° upright tilt. We assessed arterial stiffness with carotid-to-femoral pulse wave velocity (cfPWV) and sympathetic BRS during spontaneous breathing. Awake and asleep ABPM-BPs and morning surge were higher in hypertensive than normotensive subjects (all P morning surge ≥35 mmHg (median value) had higher cfPWV (11.9 ± 0.5 vs. 9.9 ± 0.4 m/s, P = 0.002) and lower sympathetic BRS (supine: −2.71 ± 0.25 vs. −3.73 ± 0.29, P = 0.011; upright: −2.62 ± 0.22 vs. −3.51 ± 0.35 bursts·100 beats−1·mmHg−1, P = 0.052) than those with morning surge 0.05), while upright total peripheral resistance was higher in hypertensive subjects with greater morning surge than those with lesser morning surge (P = 0.050). Morning surge was correlated positively with cfPWV (r = 0.59, P morning BP surge is associated with arterial stiffness and sympathetic BRS, as well as vasoreactivity during orthostasis in hypertensive seniors. PMID:23832695

  3. SYMPATHETIC STIMULATION OF THIAZIDE-SENSITIVE SODIUM-CHLORIDE COTRANSPORT IN THE GENERATION OF SALT-SENSITIVE HYPERTENSION

    Science.gov (United States)

    Terker, Andrew S.; Yang, Chao-Ling; McCormick, James A.; Meermeier, Nicholas P.; Rogers, Shaunessy L.; Grossmann, Solveig; Trompf, Katja; Delpire, Eric; Loffing, Johannes; Ellison, David H.

    2014-01-01

    Excessive renal efferent sympathetic nerve activity contributes to hypertension in many circumstances. While both hemodynamic and tubular effects likely participate, most evidence supports a major role for α-adrenergic receptors in mediating the direct epithelial stimulation of sodium retention. Recently, it was reported, however, that norepinephrine activates the thiazide-sensitive transporter, NCC, by stimulating β-adrenergic receptors. Here, we confirmed this effect and developed an acute adrenergic stimulation model to study the signaling cascade. The results show that norepinephrine increases the abundance of phosphorylated NCC rapidly (161% increase), an effect largely dependent on β-adrenergic receptors. This effect is not mediated by activation of angiotensin II receptors. We used immunodissected mouse distal convoluted tubule (DCT) to show that DCT cells are especially enriched for β1-adrenergic receptors, and that the effects of adrenergic stimulation can occur ex vivo (79% increase), suggesting they are direct. As two protein kinases, Ste20p-related Proline Alanine-rich kinase (SPAK) and Oxidative stress responsive 1 (OxSR1), phosphorylate and activate NCC, we examined their roles in norepinephrine effects. Surprisingly, norepinephrine did not affect SPAK abundance or its localization in the DCT; instead, we observed a striking activation of OxSR1. We confirmed that SPAK is not required for NCC activation, using SPAK knockout mice. Together, the data provide strong support for a signaling system involving β1- receptors in the DCT that activates NCC, at least in part via OxSR1. The results have implications regarding device- and drug-based treatment of hypertension. PMID:24799612

  4. Sympathetic stimulation of thiazide-sensitive sodium chloride cotransport in the generation of salt-sensitive hypertension.

    Science.gov (United States)

    Terker, Andrew S; Yang, Chao-Ling; McCormick, James A; Meermeier, Nicholas P; Rogers, Shaunessy L; Grossmann, Solveig; Trompf, Katja; Delpire, Eric; Loffing, Johannes; Ellison, David H

    2014-07-01

    Excessive renal efferent sympathetic nerve activity contributes to hypertension in many circumstances. Although both hemodynamic and tubular effects likely participate, most evidence supports a major role for α-adrenergic receptors in mediating the direct epithelial stimulation of sodium retention. Recently, it was reported, however, that norepinephrine activates the thiazide-sensitive NaCl cotransporter (NCC) by stimulating β-adrenergic receptors. Here, we confirmed this effect and developed an acute adrenergic stimulation model to study the signaling cascade. The results show that norepinephrine increases the abundance of phosphorylated NCC rapidly (161% increase), an effect largely dependent on β-adrenergic receptors. This effect is not mediated by the activation of angiotensin II receptors. We used immunodissected mouse distal convoluted tubule to show that distal convoluted tubule cells are especially enriched for β₁-adrenergic receptors, and that the effects of adrenergic stimulation can occur ex vivo (79% increase), suggesting they are direct. Because the 2 protein kinases, STE20p-related proline- and alanine-rich kinase (encoded by STK39) and oxidative stress-response kinase 1, phosphorylate and activate NCC, we examined their roles in norepinephrine effects. Surprisingly, norepinephrine did not affect STE20p-related proline- and alanine-rich kinase abundance or its localization in the distal convoluted tubule; instead, we observed a striking activation of oxidative stress-response kinase 1. We confirmed that STE20p-related proline- and alanine-rich kinase is not required for NCC activation, using STK39 knockout mice. Together, the data provide strong support for a signaling system involving β₁-receptors in the distal convoluted tubule that activates NCC, at least in part via oxidative stress-response kinase 1. The results have implications about device- and drug-based treatment of hypertension. © 2014 American Heart Association, Inc.

  5. The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

    Science.gov (United States)

    Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

    2014-01-01

    Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

  6. Resting sympathetic nerve activity is related to age, sex and arterial pressure but not to α2-adrenergic receptor subtype.

    Science.gov (United States)

    Maqbool, Azhar; West, Robert M; Galloway, Stacey L; Drinkhill, Mark J; Mary, David A S G; Greenwood, John P; Ball, Stephen G

    2010-10-01

    Sympathetic nerve hyperactivity has been associated with hypertension and heart failure and their cardiovascular complications. The α2-adrenergic receptors have been proposed to play a prominent role in the control of sympathetic neural output, and their malfunction to constitute a potential central mechanism for sympathetic hyperactivity of essential hypertension. Reports on the relationship between variant alleles of α2-adrenergic receptor subtypes and sympathetic drive or its effects, however, have not been consistent. Therefore, this study was planned to test the hypothesis that variant alleles of subtypes of α2-adrenergic receptors are associated with raised muscle sympathetic nerve activity (MSNA) in man. One hundred and seventy-two individuals, with a wide range of arterial pressure, were prospectively examined. Resting MSNA was quantified from multiunit bursts and from single units, and α2-adrenergic receptor subtypes were genotyped from DNA extracted from leucocytes and quantified by spectrophotometry. No significant relationships between variant alleles of any of the α2A, α2B or α2C subtypes and raised muscle sympathetic activity were found. In contrast, MSNA showed a marked significant curvilinear relationship with age and systolic pressure; sex had a small but statistically significant effect. The α2-adrenergic receptor variants had a similar frequency when hypertensive and normotensive individuals were compared. Variant alleles of three α2-adrenergic receptor subtypes were not related to resting muscle sympathetic nerve hyperactivity, indicating that their functional differences shown in vitro are not reflected in sympathetic activity in man. Age had a marked effect likely influencing arterial pressure through sympathetic activity.

  7. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation.

    Science.gov (United States)

    Barhwal, K; Hota, S K; Jain, V; Prasad, D; Singh, S B; Ilavazhagan, G

    2009-06-30

    Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex signaling pathways involved therewith limits the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. The present study was therefore aimed at investigating the potential of acetyl-l-carnitine (ALCAR), a known antioxidant that has been reported to augment neurotrophin-mediated survival mechanisms, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in the cellular defense mechanism against oxidative stress related to brain injury and neurological disorders. The study was designed to understand the mechanisms involving Nrf2 stabilization following exposure to hypobaric hypoxia. The results displayed reference memory impairment in Sprague-Dawley rats exposed to hypobaric hypoxia (7620 m) for 14 consecutive days which however improved on administration of ALCAR during hypoxic exposure. The study also revealed Nrf2 regulated augmented antioxidant response on administration of ALCAR which was through a novel tyrosine kinase A (TrkA) receptor-mediated mechanism. A decrease in free radical generation, lipid peroxidation and protein oxidation was also observed along with a concomitant increase in thioredoxin and reduced glutathione levels on administration of ALCAR during exposure to hypobaric hypoxia. The present study therefore reveals the therapeutic potential of ALCAR under conditions of hypobaric hypoxia and elucidates a novel mechanism of action of the drug.

  8. Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic nucleus

    Science.gov (United States)

    Askvig, Jason M.; Lo, David Y.; Sudbeck, Adam W.; Behm, Kathryn E.; Leiphon, Laura J.; Watt, John A.

    2012-01-01

    Previous studies have demonstrated that ciliary neurotrophic factor (CNTF) enhances survival and process outgrowth from magnocellular neurons in the paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by which CNTF facilitates these processes remain to be determined. Therefore, the aim of this study was to identify the immediate signal transduction events that occur within the rat SON following administration of exogenous rat recombinant CNTF (rrCNTF) and to determine the contribution of those intracellular signaling pathway(s) to neuronal survival and process outgrowth, respectively. Immunohistochemical and Western blot analysis demonstrated that axonal injury and acute unilateral pressure injection of 100 ng/μl of rrCNTF directly over the rat SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3) in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic organotypic explant cultures, we then demonstrated that administration of 25 ng/ml rrCNTF for 14 days significantly increased the survival and process outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the survival of OT magnocellular neurons in the SON and PVN; however, the contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains to be determined. Together, these data indicate that CNTF-induced survival of OT magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT signaling pathway. PMID:23123407

  9. Sympathetic activity of S-(+-ketamine low doses in the epidural space

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    Slobodan Mihaljevic

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: S-(+-ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S-(+-ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S-(+-ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block. METHODS: The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine was given to one group (control group while local anaesthesia and S-(+-ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non-competitive enzyme immunochemistry method (Cat Combi ELISA was used to determine the concentrations of catecholamines (adrenaline and noradrenaline. Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann-Whitney U-test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects. RESULTS: 40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S-(+-ketamine. Value p < 0.05 has been taken as a limit of statistical significance. CONCLUSIONS: Low dose of S-(+-ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S-(+-ketamine administered epidurally did not deepen sympathetic block. Adding 25 mg of S-(+-ketamine to 0

  10. Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

    Directory of Open Access Journals (Sweden)

    Lechin F

    2010-09-01

    Full Text Available Fuad Lechin1,2, Bertha van der Dijs1,2, Betty Pardey-Maldonado1, Jairo E Rivera1, Scarlet Baez1, Marcel E Lechin31Department of Pathophysiology, Sections of Neuroendocrinology, Neuropharmacology, and Neurochemistry, Instituto de Medicina Experimental, Faculty of Medicine, Universidad Central de Venezuela, Caracas; 2Instituto de Vias Digestivas Caracas, Centro Clínico Profesional, Caracas, Venezuela; 3Department of Internal Medicine, Texas A and M Health Science Center, College of Medicine, Texas, USAObjective: The aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome.Design: We measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin, using high-performance liquid chromatography with electrochemical detection, during supine resting, one minute of orthostasis, and after five minutes of exercise. In total, 22 AN patients (12 binge-eating/purging type and 10 restricting type and age-, gender-, and race-matched controls (70 ± 10.1% versus 98 ± 3.0% of ideal body weight were recruited.Results: We found that patients with AN had adrenal sympathetic overactivity and neural sympathetic underactivity, demonstrated by a predominance of circulating adrenaline over noradrenaline levels, not only during the supine resting state (52 ± 2 versus 29 ± 1 pg/mL but also during orthostasis (67 ± 3 versus 32 ± 2 pg/mL, P < 0.05 and after exercise challenge (84 ± 4 versus 30 ± 3 pg/mL, P < 0.01.Conclusion: Considering that this peripheral autonomic nervous system disorder depends on the absolute predominance of adrenomedullary C1 adrenergic nuclei over A5 noradrenergic pontine nucleus, let us ratify the abovementioned findings. The AN syndrome depends on the

  11. Revision on Renal Sympathetic Ablation in the Treatment of Resistant Hypertension.

    Science.gov (United States)

    Saraiva, Ana Filipa

    2016-01-01

    Hypertension is one of the most prevalent diseases in the world, with about 1 billion people affected and a possible increase to 1.5 billion by 2025. Despite advances in treatment, a proportion of patients remain resistant to conventional treatment and uncontrolled, and this can adversely affect future cardiovascular events and mortality. This alarming growth is already reflected in an important public health problem and one of the largest economic burdens of health, requiring new approaches and development of different strategies to fight this problem. This review will focus on the definition of resistant hypertension and its etiology, as well as in contemporary evidence supporting the usefulness of renal sympathetic denervation while addressing current and emerging devices, potential treatment indications in the future and unresolved issues that need to be addressed before renal sympathetic denervation can be adopted not only as a last resort exclusively for resistant hypertension. Finally an evaluation algorithm for patients with resistant hypertension which should be implemented before the execution of this technique will be proposed. Renal sympathetic denervation is a technique that possibly could have future implications in the population with hypertension, especially those with true resistant hypertension. This technique aims to reduce the renal sympathetic activation (a component in the pathophysiology of hypertension) through the destruction of the renal sympathetic nerves located in the adventitia of the renal arteries. There are several catheters that can be used; each with its specifications and therefore their selection should be made individually depending on the profile of the patient. However, a detailed pre-procedure evaluation is extremely important to exclude the large percentage of individuals with uncontrolled hypertension due to several factors that make it impossible to control blood pressure, but are likely to be corrected and as such should

  12. Mid-term Outcomes of An