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Sympathetic Nervous System (sympathetic + nervous_system)
Terms modified by Sympathetic Nervous System Selected AbstractsRegulation and Role of the Presynaptic and Myocardial Na+/H+ Exchanger NHE1: Effects on the Sympathetic Nervous System in Heart FailureCARDIOVASCULAR THERAPEUTICS, Issue 2 2007Kirsten Leineweber ABSTRACT In acute myocardial ischemia and in chronic heart failure, sympathetic activation with excessive norepinephrine (NE) release from and reduced NE reuptake into sympathetic nerve endings is a prominent cause of arrhythmias and cardiac dysfunction. The Na+/H+ exchanger NHE1 is the predominant isoform in the heart. It contributes to cellular acid,base balance, and electrolyte, and volume homeostasis, and is activated in response to intracellular acidosis and/or activation of guanine nucleotide binding (G) protein-coupled receptors. NHE1 mediates its signaling via protein kinases A (PKA) or C (PKC). In cardiomyocytes, NHE1 is restricted to specialized membrane domains, where it regulates the activity of pH-sensitive proteins and modulates the driving force of the Na+/Ca2+ exchanger. During acute ischemia/reperfusion and in heart failure the activity/amount of NHE1 is increased, leading to intracellular Ca2+ overload and promoting structural (apoptosis, hypertrophy) and functional (arrhythmias, hypercontraction) myocardial damage. In sympathetic nerve endings, increased NHE1 activity results in the accumulation of axoplasmic Na+ that diminishes the inward and/or favors the outward transport of NE via the neuronal norepinephrine transporter (NET). The increased NE levels within the nerve,muscle junction facilitate the sustained stimulation of myocardial ,- and ,-adrenoceptors (ARs), which in turn aggravate the increases in myocardial NHE1 activity and the associated deleterious effects. Furthermore, the responsiveness of the ,-AR declines overtime, which results in further release of NE, initiating a vicious cycle. Accordingly, NHE1 is a potential candidate for targeted intervention to suppress this feedback loop. [source] Evaluation of sympathetic vasoconstrictor response following nociceptive stimulation of latent myofascial trigger points in humansACTA PHYSIOLOGICA, Issue 4 2009Y. Kimura Abstract Aim:, Myofascial trigger points (MTrPs) are a major cause of musculoskeletal pain. It has been reported that stimulation of a latent MTrP increases motor activity and facilitates muscle pain via activation of the sympathetic nervous system. However, the magnitude of the sympathetic vasoconstrictor response following stimulation of MTrP has not been studied in healthy volunteers. The aims of this study were to (1) evaluate the magnitude of the vasoconstrictor response following a nociceptive stimulation (intramuscular glutamate) of MTrPs and a breath-hold manoeuvre (activation of sympathetic outflow) and (2) assess whether the vasoconstrictor response can be further modulated by combining a nociceptive stimulation of MTrPs and breath-hold. Methods:, Fourteen healthy subjects were recruited in this study. This study consisted of four sessions (normal breath group as control, breath-hold group, glutamate MTrP injection group and glutamate MTrP injection + breath-hold group). Skin blood flow and skin temperature in both forearms were measured with laser Doppler flowmetry and infrared thermography, respectively, in each session (before the treatment, during the treatment and after the treatment). Results:, Glutamate injection into MTrPs decreased skin temperature and blood flow in the peripheral area. The magnitudes of the reduction were comparable to those induced by the breath-hold manoeuvre, which has been used to induce sympathetic vasoconstrictor response. Conclusion:, The combination of glutamate injection into latent MTrPs together with the breath-hold manoeuvre did not result in further decrease in skin temperature and blood flow, indicating that sympathetic vasoconstrictor activity is fully activated by nociceptive stimulation of MTrPs. [source] The basic helix-loop-helix factor Hand2 regulates autonomic nervous system developmentDEVELOPMENTAL DYNAMICS, Issue 3 2005Yuka Morikawa Abstract Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash1, Phox2b, and GATA3. Here we show that the bHLH transcription factor, Hand2 (dHAND), is expressed concurrently with Mash1 during sympathetic nervous system (SNS) development and that the expression of Hand2 is not dependent on Mash1. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash1. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand2 functions to promote ANS development as part of a larger transcriptional complex. Developmental Dynamics 234:613,621, 2005. © 2005 Wiley-Liss, Inc. [source] Distributions of estrogen receptors alpha and beta in sympathetic neurons of female rats: Enriched expression by uterine innervationDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2002Elena V. Zoubina Abstract Estrogen modulates many features of the sympathetic nervous system, including cell numbers and ganglion synapses, and can induce uterine sympathetic nerve degeneration. However, distributions of estrogen receptors , and , within sympathetic neurons have not been described, and their regulation by target tissue or estrogen levels has not been explored. We used immunofluorescence and retrograde tracing to define estrogen receptor expression in sympathetic neurons at large in pre- and paravertebral ganglia and in those projecting to the uterine horns. Estrogen receptor , immunoreactivity was present in 29 ± 1%, while estrogen receptor , was expressed by 92 ± 1% of sympathetic neurons at large. The proportions of neurons expressing these receptors were comparable in the superior cervical and thoraco-lumbar paravertebral ganglia from T11 through L5, and in the suprarenal, celiac, and superior mesenteric prevertebral ganglia. Injections of FluoroGold into the uterine horns resulted in labeled neurons, with peak occurrences in T13, L1, and the suprarenal ganglion. Uterine-projecting neurons showed small but significantly greater incidence of estrogen receptor , expression relative to the neuronal population at large, whereas the proportion of uterine-projecting neurons with estrogen receptor ,-immunoreactivity was nearly threefold greater. Numbers of estrogen receptor-expressing neurons were not altered by acute estrogen administration. We conclude that the vast majority of sympathetic neurons express estrogen receptor , immunoreactive protein, whereas a smaller, presumably overlapping subset expresses the estrogen receptor ,. Expression of the latter apparently can be enhanced by target-mediated mechanisms. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 14,23, 2002 [source] Physiological effects of separation and reunion in relation to attachment and temperament in young childrenDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2007Mirjam Oosterman Abstract This study examined physiological effects of separation and reunion in a sample 3- to 6-year-old children. Using continuous ambulatory recording, changes in heart rate (HR), respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) were compared across the episodes of a separation,reunion procedure based on the strange situation. RSA decreased significantly over the course of the procedure as well as on separation from the parent and not the stranger, supporting that separation from the attachment figure elicited vagal withdrawal in young children. The absence of significant PEP effects suggest that the separation,reunion procedure, and more specifically separation from the parent, was not threatening enough to activate the sympathetic nervous system, even if children were insecure attached and inhibited with regard to strangers. Some of the variability in HR increases to reunion was explained by younger age. The findings highlight the role of the ANS as a regulatory process in the parent,child relationship. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 119,128, 2007. [source] The ontogeny of autonomic measures in 6- and 12-month-old infantsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2006Abbey Alkon Abstract The purpose of this study was to develop a standardized protocol to measure preejection period (PEP), a measure of sympathetic nervous system, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system, during resting and challenging states for 6- and 12-month-old infants and to determine developmental changes and individual stability of these measures. A 7-min reactivity protocol was administered to Latino infants at 6 months (n,=,194) and 12 months (n,=,181). Results showed: (1) it is feasible to measure PEP and RSA in infants, (2) the protocol elicited significant autonomic changes, (3) individual resting autonomic measures were moderately stable from 6 to 12 months, but reactivity measures were not stable, and (4) heart rate and RSA resting and challenge group means changed significantly from 6 to 12 months. Findings suggest that although infants' autonomic responses show developmental changes, individuals' rank order is stable from 6 to 12 months of age. © 2006 Wiley Periodicals, Inc. Dev Psyshobiol 48: 197,208, 2006. [source] Acupuncture: is it effective for treatment of insulin resistance?DIABETES OBESITY & METABOLISM, Issue 7 2010F. Liang Insulin resistance (IR) is closely associated with obesity, type 2 diabetes mellitus (T2DM), hypertension, polycystic ovary syndrome (PCOS), non-alcohol fatty liver diseases (NAFLD) and metabolic syndrome and is also a risk factor for serious diseases such as cardiovascular diseases. Pharmacological treatments available for IR are limited by drug adverse effects. Because acupuncture has been practiced for thousands of years in China, it has been increasingly used worldwide for IR-related diseases. This review analyses 234 English publications listed on the PubMed database between 1979 and 2009 on the effectiveness of acupuncture as a treatment for IR. These publications provide clinical evidence, although limited, in support of the effectiveness of acupuncture in IR. At this stage, well-designed, evidence-based clinical randomized controlled trial studies are therefore needed to confirm the effects of acupuncture on IR. Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycemia, overweight, hyperphagia, hyperlipidemia, inflammation, altered activity of the sympathetic nervous system and insulin signal defect, all of which contribute to the development of IR. In addition, acupuncture has the potential to improve insulin sensitivity. The evidence has revealed the mechanisms responsible for the beneficial effects of acupuncture, though further investigations are warranted. [source] Treatment of diabetic hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2009David S. H. Bell Insulin resistance and hyperglycaemia combine to make hypertension more prevalent in the type 2 diabetic patient. Blood pressure goals below those for the non-diabetic subject have been shown to be more effective in lowering mortality and cardiovascular events in the diabetic patient. To achieve these goals in most cases, three to five antihypertensives from different therapeutic groups need to be utilized. Suppression of the renin,angiotensin system (RAS) with angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers or a renin inhibitor should be the primary therapy. A second goal should be suppression of the sympathetic nervous system utilizing a beta-blocker that does not increase insulin resistance. The addition of a diuretic, calcium channel blocker or a vasodilator to suppressors of the RAS and sympathetic nervous system aid in achieving hypertensive goals in the diabetic patient. Achieving hypertensive goals with suppression of the RAS and sympathetic nervous system should result in a decrease in mortality and cardiovascular events in the diabetic hypertensive patient. In this review article, the benefits and disadvantages of the different antihypertensive therapies in the diabetic patient are discussed. [source] Effects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Mechanisms of renal hyporesponsiveness to ANP in heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2003A. Charloux Abstract The atrial natriuretic peptide (ANP) plays an important role in chronic heart failure (CHF), delaying the progression of the disease. However, despite high ANP levels, natriuresis falls when CHF progresses from a compensated to a decompensated state, suggesting emergence of renal resistance to ANP. Several mechanisms have been proposed to explain renal hyporesponsiveness, including decreased renal ANP availability, down-regulation of natriuretic peptide receptors and altered ANP intracellular transduction signal. It has been demonstrated that the activity of neutral endopeptidase (NEP) is increased in CHF, and that its inhibition enhances renal cGMP production and renal sodium excretion. In vitro as well as in vivo studies have provided strong evidence of an increased degradation of intracellular cGMP by phosphodiesterase in CHF. In experimental models, ANP-dependent natriuresis is improved by phosphodiesterase inhibitors, which may arise as new therapeutic agents in CHF. Sodium-retaining systems likely contribute to renal hyporesponsiveness to ANP through different mechanisms. Among these systems, the renin-angiotensin-aldosterone system has received particular attention, as angiotensin II and ANP have renal actions at the same sites and inhibition of angiotensin-converting enzyme and angiotensin-receptor blockade improve ANP hyporesponsiveness. Less is known about the interactions between the sympathetic nervous system, endothelin or vasopressin and ANP, which may also blunt ANP-induced natriuresis. To summarize, renal hyporesponsiveness to ANP is probably multifactorial. New treatments designed to restore renal ANP efficiency should limit sodium retention in CHF patients and thus delay the progression to overt heart failure. [source] ,2A and ,2C -adrenoceptor regulation in the brain: ,2A changes persist after chronic stressEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2003G. Flügge Abstract Stress-induced activation of the central nervous noradrenergic system has been suspected to induce depressive disorders. As episodes of depression often occur some time after a stress experience we investigated whether stress-induced changes in the ,2 -adrenoceptor (,2 -AR) system persist throughout a post-stress recovery period. Brains of male tree shrews were analysed after 44 days of chronic psychosocial stress and after a subsequent 10-day recovery period. Expression of RNA for ,2A and ,2C -adrenoceptors was quantified by in situ hybridization, and receptor binding was determined by in vitro receptor autoradiography. Activities of the sympathetic nervous system and of the hypothalamo,pituitary,adrenal axis were increased during chronic stress but normalized during recovery. ,2A -AR RNA in the glutamatergic neurons of the lateral reticular nucleus was elevated significantly after stress and after recovery (by 29% and 17%). In the dorsal motor nucleus of the vagus, subtype A expression was enhanced after recovery (by 33%). In the locus coeruleus, subtype A autoreceptor expression was not changed significantly. Subtype C expression in the caudate nucleus and putamen was elevated by stress (by 5 and 4%, respectively) but normalized during recovery. Quantification of 3H-RX821002 binding revealed receptor upregulation during stress and/or recovery. Our data therefore show: (i) that chronic psychosocial stress differentially regulates expression of ,2 -adrenoceptor subtypes A and C; (ii) that subtype A heteroreceptor expression is persistently upregulated whereas (iii), subtype C upregulation is only transient. The present findings coincide with post mortem studies in depressed patients revealing upregulation of ,2A -ARs. [source] Region-specific changes in sympathetic nerve activity in angiotensin II,salt hypertension in the ratEXPERIMENTAL PHYSIOLOGY, Issue 1 2010John W. Osborn It is now well accepted that many forms of experimental hypertension and human essential hypertension are caused by increased activity of the sympathetic nervous system. However, the role of region-specific changes in sympathetic nerve activity (SNA) in the pathogenesis of hypertension has been difficult to determine because methods for chronic measurement of SNA in conscious animals have not been available. We have recently combined indirect, and continuous and chronic direct, assessment of region-specific SNA to characterize hypertension produced by administration of angiotensin II (Ang II) to rats consuming a high-salt diet (Ang II,salt hypertension). Angiotensin II increases whole-body noradrenaline (NA) spillover and depressor responses to ganglionic blockade in rats consuming a high-salt diet, but not in rats on a normal-salt diet. Despite this evidence for increased ,whole-body SNA' in Ang II,salt hypertensive rats, renal SNA is decreased in this model and renal denervation does not attenuate the steady-state level of arterial pressure. In addition, neither lumbar SNA, which largely targets skeletal muscle, nor hindlimb NA spillover is changed from control levels in Ang II,salt hypertensive rats. However, surgical denervation of the splanchnic vascular bed attenuates/abolishes the increase in arterial pressure and total peripheral resistance, as well as the decrease in vascular capacitance, observed in Ang II,salt hypertensive rats. We hypothesize that the ,sympathetic signature' of Ang II,salt hypertension is characterized by increased splanchnic SNA, no change in skeletal muscle SNA and decreased renal SNA, and this sympathetic signature creates unique haemodynamic changes capable of producing sustained hypertension. [source] Age-related analysis of insulin resistance, body weight and arterial pressure in the Zucker fatty ratEXPERIMENTAL PHYSIOLOGY, Issue 1 2009Francesco Di Nardo The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n= 22), between 7 and 16 weeks of age, compared with an age-matched control group of Zucker lean rats (ZLRs, n= 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, SG, and insulin sensitivity, SI, from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between SG and age in both ZFR and ZLR groups. No significant changes in mean SG between the two groups indicated no alteration of glucose-mediated glucose disposal. Estimates of SI from individual ZFRs were independent of age and, on average, showed 83% reduction (P < 0.001) compared with the ZLR group. Despite the lack of alteration of SI with age, the ZFR group showed an age-related increase of MAP, which correlated with increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin resistance is fully established at the age of 7 weeks and remains practically unaltered until at least the sixteenth week. An age-related increase in arterial pressure, observed in this strain, relates more properly to increasing BW, rather than insulin resistance. Development of hypertension with increasing age and BW may result from an enhanced insulin-mediated activity of the sympathetic nervous system, as observed in our previously reported study. [source] A sympathetic view of the sympathetic nervous system and human blood pressure regulationEXPERIMENTAL PHYSIOLOGY, Issue 6 2008Michael J. Joyner New ideas about the relative importance of the autonomic nervous system (and especially its sympathetic arm) in long-term blood pressure regulation are emerging. It is well known that mean arterial blood pressure is normally regulated in a fairly narrow range at rest and that blood pressure is also able to rise and fall ,appropriately' to meet the demands of various forms of mental, emotional and physical stress. By contrast, blood pressure varies widely when the autonomic nervous system is absent or when key mechanisms that govern it are destroyed. However, 24 h mean arterial pressure is still surprisingly normal under these conditions. Thus, the dominant idea has been that the kidney is the main long-term regulator of blood pressure and the autonomic nervous system is important in short-term regulation. However, this ,renocentric' scheme can be challenged by observations in humans showing that there is a high degree of individual variability in elements of the autonomic nervous system. Along these lines, the level of sympathetic outflow, the adrenergic responsiveness of blood vessels and individual haemodynamic patterns appear to exist in a complex, but appropriate, balance in normotension. Furthermore, evidence from animals and humans has now clearly shown that the sympathetic nervous system can play an important role in longer term blood pressure regulation in both normotension and hypertension. Finally, humans with high baseline sympathetic traffic might be at increased risk for hypertension if the ,balance' among factors deteriorates or is lost. In this context, the goal of this review is to encourage a comprehensive rethinking of the complexities related to long-term blood pressure regulation in humans and promote finer appreciation of physiological relationships among the autonomic nervous system, vascular function, ageing, metabolism and blood pressure. [source] Angiotensin II-based hypertension and the sympathetic nervous system: the role of dose and increased dietary salt in rabbitsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Fiona D. McBryde There is accumulating evidence that angiotensin II may exert its hypertensive effect through increasing sympathetic drive. However, this action may be dependent on the dose of angiotensin II as well as salt intake. We determined the effect of different doses of angiotensin II and different levels of salt intake on neurogenic pressor activity. We also examined the effect of renal denervation. New Zealand White rabbits were instrumented to continuously measure arterial pressure. The depressor response to the ganglionic blocker pentolinium tartrate (5 mg kg,1) was used to assess pressor sympathetic drive on days 0, 7 and 21 of a 20 or 50 ng kg,1 min,1 continuous i.v. angiotensin II infusion. A 50 ng kg,1 min,1 infusion caused an immediate increase in pressure (23 ± 5 mmHg), whereas a 20 ng kg,1 min,1 infusion caused a slow increase in pressure, peaking by day 12 (17 ± 4 mmHg). The ganglionic blockade profiles indicated sympathoinhibition in the 50 ng kg,1 min,1 group by day 7 and sympathoinhibition in the 20 ng kg,1 min,1 group at day 21, corresponding to the development of hypertension. Animals receiving increased dietary salt (0.9% NaCl in drinking water), however, showed a similar slow increase in pressure with 20 ng kg,1 min,1 angiotensin II (16 ± 5 mmHg) but no sympathoinhibition at day 21. Bilateral renal denervation delayed the onset but not the extent of hypertension in this group. We conclude that different doses of angiotensin II produce distinct profiles of hypertension and associated changes in pressor sympathetic drive and that increased dietary salt intake disrupts the normal sympathoinhibitory response to angiotensin II-based hypertension. [source] Comparison of the firing patterns of human postganglionic sympathetic neurones and spinal , motoneurones during brief burstsEXPERIMENTAL PHYSIOLOGY, Issue 1 2004Vaughan G. Macefield Focal recordings from individual postganglionic sympathetic neurones in awake human subjects have revealed common firing properties. One of the most striking features is that they tend to fire only once per sympathetic burst. Why this should be so is not known, but we propose that the short duration of the burst may limit the number of times a sympathetic neurone can fire. Indeed, while the normal variation in cardiac interval and burst duration is too narrow to reveal a correlation between burst duration and the number of spikes generated, we know that spike generation is doubled when burst duration is doubled following ectopic heart beats. To test the hypothesis that the burst duration constrains the firing of individual sympathetic neurones to one per burst, we used the human skeletomotor system as a model for the sympathetic nervous system, which allowed us to vary burst duration and amplitude experimentally. Intramuscular recordings were made from 27 single motor units (, motoneurones) in the tibialis anterior or soleus muscles of seven subjects; multiunit EMG activity was recorded via surface electrodes and blood pressure was recorded continuously. Subjects were instructed to generate EMG bursts of varying amplitude in the intervals between heart beats. By constraining the firing of , motoneurones to brief (,400 ms) bursts we could emulate real sympathetic bursts. Individual motoneurones generated 0,7 spikes during the emulated sympathetic bursts, with firing patterns similar to those exhibited by real sympathetic neurones. Eleven motor units showed significant positive linear correlations between the number of spikes they generated within a burst and its amplitude, whereas for 17 motor units there were significant positive correlations between the number of spikes and burst duration. This indicates that burst duration is a major determinant of the number of times an , motoneurone will fire during a brief burst, and we suggest that the same principle may explain the firing pattern typical of human sympathetic neurones. [source] Aberrant splicing of the PTPRD gene mimics microdeletions identified at this locus in neuroblastomasGENES, CHROMOSOMES AND CANCER, Issue 3 2008Prakash Nair Neuroblastoma (NBL), a pediatric tumor arising from precursor cells of the sympathetic nervous system, is characterized by numerous recurrent large-scale chromosomal imbalances. High resolution oligonucleotide array CGH analysis of NBL has previously identified microdeletions that are confined to the 5, UTR of the protein tyrosine phosphatase receptor D (PTPRD) gene, implicating this gene in the pathogenesis of these tumors. Here, we demonstrate that the 5, UTR of this gene, consisting of 11 noncoding exons, is also aberrantly spliced in >50% of NBL primary tumors and cell lines. The loss of exons from the 5, UTR region through aberrant splicing results in aberrant mRNA isoforms that are similar to those generated through microdeletions. The aberrant splicing or microdeletion of 5, UTR exons in such a high proportion of tumors indicates that loss of these exons dys-regulates the mRNA sequence. To further validate the role of PTPRD in NBL, we have examined the expression of this gene in normal fetal adrenal neuroblasts (the cell of origin of NBL) and in tumors from patients with either low stage or high stage disease. This gene is expressed at lower levels in high stage NBL tumors, particularly those with amplification of MYCN, relative to low stage tumors or normal fetal adrenal neuroblasts, consistent with the possibility that loss of the 5, UTR exons have destabilized the mRNA. © 2007 Wiley-Liss, Inc. [source] Migraine: A Chronic Sympathetic Nervous System DisorderHEADACHE, Issue 1 2004Stephen J. Peroutka MD Objective.,To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine. Background.,Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy. Methods.,A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders. Results.,The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors. Conclusions.,The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache. [source] Sleep apnea and dialysis therapies: Things that go bump in the night?HEMODIALYSIS INTERNATIONAL, Issue 4 2007Mark L. UNRUH Abstract Sleep apnea has been linked to excessive daytime sleepiness, depressed mood, hypertension, and cardiovascular disease in the general population. The prevalence of severe sleep apnea in the conventional thrice-weekly hemodialysis population has been estimated to be more than 50%. Sleep apnea leads to repetitive episodes of hypoxemia, hypercapnia, sleep disruption, and activation of the sympathetic nervous system. The hypoxemia, arousals, and intrathoracic pressure changes associated with sleep apnea lead to sympathetic activation, endothelial dysfunction, oxidative stress, and inflammation. Because sleep apnea has been shown to be widespread in the conventional dialysis population, it may be that sleep apnea contributes substantially to the sleepiness, poor quality of life, and cardiovascular disease found in this population. The causal links between conventional dialysis and sleep apnea remain speculative, but there are likely multiple factors related to volume status and azotemia that contribute to the high rate of severe sleep apnea in dialysis patients. Both nocturnal automated peritoneal dialysis and nocturnal hemodialysis have been associated with reduced severity of sleep apnea. Nocturnal dialysis modalities may provide tools to increase our understanding of the uremic sleep apnea and may also provide therapeutic alternatives for end-stage renal disease patients with severe sleep apnea. In conclusion, sleep apnea is an important, but overlooked, public health problem for the dialysis population. The impact of sleep apnea treatment in this high-risk population may include reduced sleepiness, better mood and blood pressure, and lowered risk of cardiovascular disease. [source] Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system,,HEPATOLOGY, Issue 4 2006Anne Lenaerts The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications. (HEPATOLOGY 2006;44:844,849.) [source] Basic Study of a Ship Navigator's Stress Using Salivary Amylase ActivityIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 5 2009Koji Murai Member Abstract Evaluation of ship handling mental workload/training has usually depended on professionals (captain, pilot) who have a lot of experience on board. We are attempting to evaluate a ship navigator's mental workload (stress) based on a physiological index. The physiological indices, heart rate variability (R-R interval) and nasal temperature, are good indices of the stress found in ship handling. It is best if we get response and evaluation results quickly on the spot. A recent study shows salivary amylase activity is induced by the sympathetic nervous system; however, a research on ship navigator has not yet accepted worldwide. This article proposes that salivary amylase activity shows a ship navigator's stress during ship handling. Copyright © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] Bioinspired Electrochemically Tunable Block Copolymer Full Color PixelsADVANCED MATERIALS, Issue 30 2009Joseph J. Walish A variety of fish and cephalopods use tunable 1D photonic crystals to signal and display information. These animals control the color of the reflectors through chemical secretion by the sympathetic nervous system, which reduces the distance between platelets in reflective cells. This control can be mimicked by a bioinspired, 1D photonic block copolymer that is made tunable (see figure) by the production of chemical species through electrochemistry. [source] Neuropeptide Y and alpha-melanocyte-stimulating hormone: interaction in obesity and possible role in the development of hypertensionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008M. Baltatzi Summary Aim:, Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha-melanocyte-stimulating hormone (a-MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity. Methods:, Analysis of the pertinent bibliography published in PubMed database. Results:, Leptin is produced in the adipose tissue directly correlated with fat tissue mass. Leptin acts on two distinct neural populations in the hypothalamus: the first expresses the orexigenic peptides NPY and agouti-related protein (AgRP), the second pro-opiomelanocortin (POMC). The activation of POMC neurons increases the production of the anorexigenic hormone a-MSH and inhibits the release of NPY and AgRP. In addition, the hypothalamus integrates the neuroendocrine systems with the autonomic nervous system and controls the activity of the latter. Stimulation of hypothalamic nuclei elicits sympathetic responses including blood pressure elevation. Both NPY and a-MSH appears to be implicated in the hypothalamic regulation of sympathetic nervous system (SNS) activity. Conclusion:, Alterations in leptin, NPY and a-MSH are frequently observed in obesity and might stimulate SNS activity, contributing to the development of hypertension in obese patients. These neuropeptides might provide a pathophysiologic link between excess weight and hypertension. However, more research is needed before the pharmacologic manipulation of these complex neuroendocrine systems can be applied in the treatment of obesity and hypertension. [source] Impaired Energetic Metabolism After Central Leptin Signaling Leads to Massive Appendicular Bone Loss in Hindlimb-Suspended Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Aline Martin Abstract We previously showed in rats that the leptin effects on bone were dose dependent. Positive effects were observed when serum leptin concentration was in a physiological range. In contrast, important increases in serum leptin levels led to negative effects on bone formation similar to those reported after intracerebroventricular leptin administration in mice. To clarify whether leptin effects on bone depend on administration route and/or animal model, female rats were hindlimb unloaded or not and treated either with intracerebroventricular infusion of leptin or vehicle for 14 days. By increasing cerebrospinal fluid (CSF) leptin concentration, intracerebroventricular infusion of leptin significantly reduced food intake and consequently body weight, abdominal fat, and lean mass of the animals. Leptin infusion inhibited bone elongation over the 14 days and blunted cortical bone thickening at the femoral diaphysis site. Interestingly, leptin effects were site dependent in the cancellous bone envelopes, because tibia metaphysis BMD was lower and lumbar spine BMD was higher under intracerebroventricular leptin. Treated groups showed reduced bone remodeling independently of hindlimb unloading. Multiple downstream pathways were implicated in the mediation of these negative leptin effects on bone including not only stimulation of the sympathetic nervous system but also a decrease in somatotropic axis activity. Therefore, the intracerebroventricular leptin-induced bone loss could be largely related to the concurrent alteration of energetic and metabolic status. In summary, our study supports the hypothesis of a concentration-dependent balance between peripheral and central control of leptin on bone. [source] The outcome of tactile touch on oxytocin in intensive care patients: a randomised controlled trialJOURNAL OF CLINICAL NURSING, Issue 19 2008Maria Henricson Aim., To explore the effects of five-day tactile touch intervention on oxytocin in intensive care patients. The hypotheses were that tactile touch increases the levels of oxytocin after intervention and over a six-day period. Background., Research on both humans and animals shows a correlation between touch and increased levels of oxytocin which inspired us to measure the levels of oxytocin in arterial blood to obtain information about the physiological effect of tactile touch. Design., Randomised controlled trial. Method., Forty-four patients from two general intensive care units, were randomly assigned to either tactile touch (n = 21) or standard treatment , an hour of rest (n = 23). Arterial blood was drawn for measurement of oxytocin, before and after both treatments. Results., No significant mean changes in oxytocin levels were found from day 1 to day 6 in the intervention group (mean ,3·0 pM, SD 16·8). In the control group, there was a significant (p = 0·01) decrease in oxytocin levels from day 1 to day 6, mean 26·4 pM (SD 74·1). There were no significant differences in changes between day 1 and day 6 when comparing the intervention group and control group, mean 23·4 pM (95% CI ,20·2,67·0). Conclusion., Our hypothesis that tactile touch increases the levels of oxytocin in patients at intensive care units was not confirmed. An interesting observation was the decrease levels of oxytocin over the six-day period in the control group, which was not observed in the intervention group. Relevance to clinical practice., Tactile touch seemed to reduce the activity of the sympathetic nervous system. Further and larger studies are needed in intensive care units to confirm/evaluate tactile touch as a complementary caring act for critically ill patients. [source] Review: Energy regulation and neuroendocrine,immune control in chronic inflammatory diseasesJOURNAL OF INTERNAL MEDICINE, Issue 6 2010R. H. Straub Abstract., Straub RH, Cutolo M, Buttgereit F, Pongratz G (University Hospital Regensburg, Regensburg, Germany; University of Genova, Genova, Italy; and Charité University Medicine Berlin, Berlin, Germany). Energy regulation and neuroendocrine,immune control in chronic inflammatory diseases (Review). J Intern Med 2010; 267:543,560. Energy regulation (EnR) is most important for homoeostatic regulation of physiological processes. Neuroendocrine pathways are involved in EnR. We can separate factors that provide energy-rich fuels to stores [parasympathetic nervous system (PSNS), insulin, insulin-like growth factor-1, oestrogens, androgens and osteocalcin] and those that provide energy-rich substrates to consumers [sympathetic nervous system (SNS), hypothalamic,pituitary,adrenal axis, thyroid hormones, glucagon and growth hormone]. In chronic inflammatory diseases (CIDs), balanced energy-rich fuel allocation to stores and consumers, normally aligned with circadian rhythms, is largely disturbed due to the vast fuel consumption of an activated immune system (up to 2000 kJ day,1). Proinflammatory cytokines such as tumour necrosis factor or interleukins 1, and 6, circulating activated immune cells and sensory nerve fibres signal immune activation to the rest of the body. This signal is an appeal for energy-rich fuels as regulators are switched on to supply energy-rich fuels (,energy appeal reaction'). During evolution, adequate EnR evolved to cope with nonlife-threatening diseases, not with CIDs (huge negative selection pressure and reduced reproduction). Thus, EnR is inadequate in CIDs leading to many abnormalities, including sickness behaviour, anorexia, hypovitaminosis D, cachexia, cachectic obesity, insulin resistance, hyperinsulinaemia, dyslipidaemia, fat deposits near inflamed tissue, hypoandrogenaemia, mild hypercortisolaemia, activation of the SNS (hypertension), CID-related anaemia and osteopenia. Many of these conditions can contribute to the metabolic syndrome. These signs and symptoms become comprehensible in the context of an exaggerated call for energy-rich fuels by the immune system. We propose that the presented pathophysiological framework may lead to new therapeutical approaches and to a better understanding of CID sequence. [source] Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illnessJOURNAL OF INTERNAL MEDICINE, Issue 2 2006P. E. MOLINA Abstract. Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic,pituitary,adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed. [source] The inflammatory reflex , IntroductionJOURNAL OF INTERNAL MEDICINE, Issue 2 2005J. ANDERSSON Abstract. Sepsis is the third leading cause of death in the developed world. Despite recent advances in intensive care treatment and the discovery of antibiotics, sepsis remains associated with a high mortality rate. The pathogenesis of sepsis is characterized by an overwhelming systemic inflammatory response that is central to the development of lethal multiple organ failure. This volume of the Journal of Internal Medicine contains three reviews addressing novel aspects of a system we are only beginning to understand , the interactions between the immune and the nervous systems, the ,neuro-immune axis'. Tracey (Nature 2002; 420: 853) recently discovered that the nervous system, through the vagus nerve, can modulate circulating TNF- , levels induced by microbial invasion or tissue injury. This cholinergic anti-inflammatory pathway is mediated primarily by nicotinic acetylcholine receptors on tissue macrophages , the pathway leads to decreased production of proinflammatory cytokines. The author reports that treatment with the acetylcholine receptor agonist, nicotine, modulates this system and reduces mortality in ,established' sepsis. Watkins and Maier (J Intern Med 2005; 257: 139) illustrate that pathological pain (induced by inflammation) is not simply a strict neuronal phenomenon, but is a component of the immune response, and is modulated by peripheral immune cells and spinal cord glia cells. This may be of importance for future development of novel drugs for neuropathic pain as well as our understanding of increased risks for infections in anaesthetic skin areas. Blalock (J Immunol 1984; 132: 1067) elucidates the possibility that the immune system actually functions as the sixth sense, sensing microbes and microbial toxins that we cannot see, hear, taste, touch or smell. Activation of the sympathetic nervous system also has predominantly anti-inflammatory effects that are mediated through direct nerve to immune cell interaction or through the adrenal neuro-endocrine axis. [source] Acupuncture in Polycystic Ovary Syndrome: Current Experimental and Clinical EvidenceJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2008E. Stener-Victorin This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity. PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life. Despite extensive research, little is known about the aetiology of PCOS. The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation. [source] Metyrapone-Induced Glucocorticoid Depletion Modulates Tyrosine Hydroxylase and Phenylethanolamine N -Methyltransferase Gene Expression in the Rat Adrenal Gland by a Noncholinergic Transsynaptic ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2003C. Laborie Abstract The hypothalamic corticotropin-releasing hormone system and the sympathetic nervous system are anatomically and functionally interconnected and hormones of the hypothalamic-pituitary-adrenocortical axis contribute to the regulation of catecholaminergic systems. To investigate the role of glucocorticoids on activity of the adrenal gland, we analysed plasma and adrenal catecholamines, tyrosine hydroxylase (TH) and phenylethanolamine N -methyltransferase (PNMT) mRNA expression in rats injected with metyrapone or dexamethasone. Metyrapone-treated rats had significantly lower epinephrine and higher norepinephrine production than control rats. Metyrapone increased TH protein synthesis and TH mRNA expression whereas its administration did not affect PNMT mRNA expression. Dexamethasone restored plasma and adrenal epinephrine concentrations and increased PNMT mRNA levels, which is consistent with an absolute requirement of glucocorticoids for PNMT expression. Adrenal denervation completely abolished the metyrapone-induced TH mRNA expression. Blockage of cholinergic neurotransmission by nicotinic or muscarinic receptor antagonists did not prevent the metyrapone-induced rise in TH mRNA. Finally, pituitary adenylate cyclase activating polypeptide (PACAP) adrenal content was not affected by metyrapone. These results provide evidence that metyrapone-induced corticosterone depletion elicits transsynaptic TH activation, implying noncholinergic neurotransmission. This may involve neuropeptides other than PACAP. [source] | ||||||||||||||||||||||||||||||||||