Plasma Levels Of Neuropeptide Research Articles

Nape seven needles combined with pressing moxibustion for cervical vertigo: a randomized controlled trial

To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV). A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups. After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05). Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.

Neuropeptide Y attenuates cardiac remodeling and deterioration of function following myocardial infarction

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype invivo and invitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.

Adipocytokine and appetite-regulating hormone response to weight loss in adolescents with obesity: Impact of weight loss magnitude

ObjectiveThe aim of this study was to investigate the association between the magnitude of weight loss (WL) and serum concentrations of the main adipocytokines and appetite-regulating hormones in adolescents with obesity. MethodsAfter completion of informed consent,108 adolescents with obesity (14–19 y of age; postpubertal) were submitted to clinical, nutritional, psychological, physical exercise, and physiotherapy support for 1 y. Body composition (BC) and plasma levels of neuropeptides (neuropeptide Y [NPY], agouti-related peptide [AgRP], and α-melanocyte-stimulating hormone [α-MSH]) and leptin were measured at baseline and post-intervention. ResultsAfter therapy, adolescents who lost <10% body weight and <10% body weight (were compared. Both groups presented improvements in BC and reduced leptin. The Δα-MSH, Δα-MSH/AgRP ratio, and Δα-MSH/NPY ratio were lower and AgRP and NPY variations were higher in the low weight loss group. The leptin concentration was close to normal in the high weight loss only. The ΔWeight, Δα-MSH and Δleptin were associated with body fat loss by multiple linear regressions for all samples. ConclusionWeight loss >10% seems to reverse obesity-induced hyperleptinemia while stabilizing the neuropeptides that control appetite in adolescents with obesity. We were able to produce a prognostic mathematical model to predict body fat loss using weight, leptin, and α-MSH variations.

Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

Su1912 μ Opioid Receptor Activation Protects Against Intestinal Ischemia-Reperfusion Injury in Mice Through Different Pathways During Early and Late Phase of Reperfusion

Background: Neuropeptide S (NPS) is expressed by gastrointestinal (GI) enteroendocrine cells and macrophages in rat and man. Polymorphisms of the NPS receptor are linked to increased risk of inflammatory bowel disease as well as motor and sensory disturbances of the gut, suggesting a role for NPS in GI disorders. Further knowledge of NPS effects on motility and inflammation is needed. Methods: Studies of motility were carried out in rats with electrodes implanted in the small bowel. NPS was infused IV for 60 min and effects on myoelectrical activity were recorded. Motility effects of NPS were further studied as luminal pressure changes in anaesthetized rats where the proximal small intestine with intact blood supply was perfused with saline for motility recordings. Tissue samples were obtained from rats for evaluation of gene expression and protein elaboration of inflammatory biomarkers. Muscle strips of the human stomach, small intestine and colon were used for pharmacological analysis in organ baths of motility responses to NPS. Localization of the NPS receptor was done with fluorescent-protein tagging using Cy3-NPS. Plasma levels of NPS were measured using ELISA in 5 healthy and 14 IBD patients before and after meal. Results: In conscious rats, NPS 1 nmol kg-1min-1 increased irregular spiking, 4 nmol kg-1min-1 reduced spiking and increased the MMC cycle length (P=0.005). In anesthetized rats, NPS 0.01-1 nmol kg-1min-1 dose-dependently reduced small bowel motility (P<0.001). In rats, NPS also increased the mRNA expression of iNOS, and CXCL1 and IL-1β at the protein level. In human, fluorescent protein-tagging showed the NPS receptor primarily to be present in enolase-positive nerve fibers, but some scattered also in muscle tissue. In organ baths, NPS 1-100 nM caused TTX-dependent relaxations of the smooth muscle. We found no detectable levels of NPS in plasma of neither healthy subjects nor IBD patients. Conclusion: NPS has a smooth muscle-relaxing effect in the GI tract and dampens myoelectrical and contractile motor activity of the small bowel. This is achieved primarily through an inhibition of nerve-mediated relaxation of smooth muscle cells. Circulating NPS levels in humans are undetectable in healthy subjects and in active IBD. This implies that NPS exerts its inhibitory function by a paracrine or neurocrine mechanism in the gut. NPS seems also capable of intervening with inflammation by increasing gut cytokines and iNOS expression.

Su1911 Neuropeptide S: Effects on Motility, Contractility and Inflammation in the Rat and Human Gastrointestinal Tract

Background: Neuropeptide S (NPS) is expressed by gastrointestinal (GI) enteroendocrine cells and macrophages in rat and man. Polymorphisms of the NPS receptor are linked to increased risk of inflammatory bowel disease as well as motor and sensory disturbances of the gut, suggesting a role for NPS in GI disorders. Further knowledge of NPS effects on motility and inflammation is needed. Methods: Studies of motility were carried out in rats with electrodes implanted in the small bowel. NPS was infused IV for 60 min and effects on myoelectrical activity were recorded. Motility effects of NPS were further studied as luminal pressure changes in anaesthetized rats where the proximal small intestine with intact blood supply was perfused with saline for motility recordings. Tissue samples were obtained from rats for evaluation of gene expression and protein elaboration of inflammatory biomarkers. Muscle strips of the human stomach, small intestine and colon were used for pharmacological analysis in organ baths of motility responses to NPS. Localization of the NPS receptor was done with fluorescent-protein tagging using Cy3-NPS. Plasma levels of NPS were measured using ELISA in 5 healthy and 14 IBD patients before and after meal. Results: In conscious rats, NPS 1 nmol kg-1min-1 increased irregular spiking, 4 nmol kg-1min-1 reduced spiking and increased the MMC cycle length (P=0.005). In anesthetized rats, NPS 0.01-1 nmol kg-1min-1 dose-dependently reduced small bowel motility (P<0.001). In rats, NPS also increased the mRNA expression of iNOS, and CXCL1 and IL-1β at the protein level. In human, fluorescent protein-tagging showed the NPS receptor primarily to be present in enolase-positive nerve fibers, but some scattered also in muscle tissue. In organ baths, NPS 1-100 nM caused TTX-dependent relaxations of the smooth muscle. We found no detectable levels of NPS in plasma of neither healthy subjects nor IBD patients. Conclusion: NPS has a smooth muscle-relaxing effect in the GI tract and dampens myoelectrical and contractile motor activity of the small bowel. This is achieved primarily through an inhibition of nerve-mediated relaxation of smooth muscle cells. Circulating NPS levels in humans are undetectable in healthy subjects and in active IBD. This implies that NPS exerts its inhibitory function by a paracrine or neurocrine mechanism in the gut. NPS seems also capable of intervening with inflammation by increasing gut cytokines and iNOS expression.

Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat

Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant (P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs (n = 19) compared with WKYs (n = 16) but not in response to exogenous NE (0.025-5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [(3)H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [(3)H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.

Effect of pilocarpine on substance P and calcitonin gene-related peptide releases correlate with salivary secretion in human saliva and plasma

Pilocarpine, a muscarinic receptor agonist, has been used for the treatment of dry mouth. Salivary glands are supplied with nerve fibres that contain neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP), which are important modulators of salivation. It is known that measurement of salivary and plasma levels of neuropeptides is useful for assessing the dose-pharmacological effect relationship of drugs. The relationship between the action of pilocarpine and neuropeptides in humans has not been studied. Moreover, studies evaluate the usefulness of drug salivary levels in the pharmacological evaluation of drugs are scarce. The aim of this study was to examine the effects of pilocarpine on the levels of substance P-, CGRP- and VIP-like immunoreactive substances (IS) in saliva and plasma taken in healthy humans. Five healthy male subjects participated in this study. Pilocarpine tablet (10 mg) or placebo tablet was orally administered with 100 mL of water. Each subject was administered placebo and drug with an interval of 4 weeks in between. Saliva was sampled before and at 20, 40, 60, 90, 120, 180 and 240 min after administration of the test substances. Venous blood samples (10 mL) were also taken from a forearm vein at each time interval. The samples were then enzyme immunoassayed using a highly sensitive system for substance P-, CGRP- and VIP-IS. The amount of saliva was measured by the Saxon test. A single oral administration of pilocarpine increased the release of salivary substance P-IS (the area under the concentration-time curve: AUC(0→240 min)) compared with the placebo. Pilocarpine also significantly increased the release of salivary CGRP-IS (AUC(0→240 min)). Pilocarpine significantly increased the release of plasma CGRP-IS. The salivary volume correlated with the salivary level of substance P and CGRP-IS (r = 0·84, P < 0·05 and r = 0·59, P < 0·05, respectively). AUC(0→240 min) for substance P-IS in saliva correlated with that for plasma (r = 0·78, P < 0·05). Pilocarpine increases the release of salivary substance P and CGRP-IS. This suggests that one mechanism by which pilocarpine improves dry mouth is by local stimulation of neuropeptidergic nerves. Moreover, saliva levels of substance P showed good correlation with the plasma levels. The substance P levels in saliva and plasma may be good indicators of the effects of drugs used in dry mouth/xerostomic patients.

Elevated plasma levels of neuropeptide Y in female fibromyalgia patients.

Neuropeptide Y(NPY) co-exists with norepinephrine in the sympathetic nervous system, and NPY may represent the sympathetic-neuronal output. Fibromyalgia syndrome (FMS) patients have perturbations in the hypothalmic-pituitary-adrenal (HPA) axis and in the sympathetic stress axis as well. As opioid peptides, monoamines and sex steroids are integrated in the regulation of stress, it is interesting to further explore the role of NPY in FMS patients, as they show many symptoms that are related to perturbations of those systems.In this study, plasma NPY levels were assessed in subgroups of FMS patients: cyclic (regular menstrual cycles), non-cyclic (post-menopausal), depressed and non-depressed patients. In order to examine whether pain and other symptoms seen in FMS patients are correlated to the NPY levels, the patients were also registering 15 different symptoms daily during 28 days. Sex and age-matched healthy controls were recruited for comparisons. Non-parametric tests were used for the statistical analyses.The results showed that the NPY levels were significantly elevated in the patients compared to the controls. In the luteal phase of the cyclic patients, the levels of the peptide were higher than in the corresponding controls. For the non-cyclic patients, there was a positive correlation between physical symptoms and NPY levels, however, pain per se did not reach the significant level of correlation. The non-depressed patients had the same levels of NPY as the depressed FMS patients, who also had a positive correlation between anxiety and NPY levels.These results suggest that FMS patients have an altered activity in the NPY system, most likely due to prolonged and/or repeated stress, and that the hormonal state and time of the menstrual cycle also may be of importance in the complex pathophysiologic mechanism behind the development of FMS. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Plasma levels of neuropeptides and metabolic hormones, and sleepiness in obstructive sleep apnea

Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients. We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score ≥ 13 (mean ± SD, 15.7 ± 2.3) and 132 patients without EDS as defined by an ESS score ≤ 9 (6.5 ± 1.9). All patients had an apnea-hypopnea index (AHI) ≥ 20 h(-1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 ± 11.2 yrs vs. 50.7 ± 9.9 yrs), body mass index (BMI) (31.8 ± 5.6 kg m(-2) vs. 32.1 ± 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 ± 19.1 h(-1) vs. 43 ± 19.2 h(-1)). OSA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than OSA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time. Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep-wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA).

Relationship between plasma neuropeptide Y and serum nitricoxide synthase for patients with acute cerebral infarction

Objective To observe the dynamic changes in plasma levels of neuropeptide Y (NPY) in patients with acute cerebral infarction (ACI) and the serum nitric oxide synthase (NOS) in order to find out the relationship between each other as well as their clinical significance. Method A prospective and control study was done in 30 patients with ACI including 21 male and 9 female with average age of (58.07 ± 12. 1S) years admitted from May 2008 to March 2009. These patients hit the diagnostic criteria for cerebral infarction (CI) set by the Chinese Society for Neruoscience and the Chinese Association of Neurosurgery in 1996 for their first attack of CI was treated within 48 hours. Patients with acute myocardial infarction, peripheral vascular disease, infection, tumor,or severe organic functional impairment, etc within six months were excluded. Another 27 healthy subjects asking for routine physical examination including 15 male and 12 female with average age of (55.00± 11.03) years were included as control group at the same period. The two groups were comparable. The blood samples of fasted subjects of control group and CI patients 48 hours after and within 10 days after attack were taken to examine the level of NPY by using radioimmunoassay and the level of serum NOS by using chemical colorimetry. The size of responsible focus of CI was calculated, and the degree of neurological deficits were estimated with Stroke Scales set by the American National Institutes Of Health (NIHSS). The chi-square test was used for constituent ratios within samples, while t -test was applied to analysis of differences between two groups, and linear was used for bivariate simple correlation analysis. Results (1) There was no significant difference in NPY between two groups. (2) The level of constructional NOS (cNOS) within 48 hours after attack in CI group was significantly lower than that in control group, and it was significantly and negatively correlated with the size of infarction and the NIHSS scores at the same period, whereas it significantly and positively correlated with difference in NIHSS scores, while it increased more significantly 10 days after attack than it did within 48 hours after attack. (3) The level of inducible NOS (iNOS) within 48 hours after attack in CI group was significantly higher than that in control group, and it was significantly and positively correlated with the size of infarctionand NIHSS scores at the same period, and it significantly and negatively crrelated with the difference in NIHSS scores, while it decreased more significantly 10 days after attack than it did within 48 hours after attack. (4) The level of NPY was not correlated with both cNOS and iNOS in CI group. The difference in levels of NPY was negatively and significantly correlated with the difference in levels of cNOS. Conclusions There was no significant change in plasma NPY level in ACI patients, and it was not correlated significantly with the disease itself. The serum cNOS was negatively correlated with the disease itself significantly within 48 hours after attack. The iNOS level was positively correlated with the disease itself significantly, and it reflected the severity of CI within 48 hours after attack. The changes of NPY level in plasma were significantly and negatively correlated with the changes of cNOS level in serum within 48 hours and 10 days after attack. Key words: Acute cerebral infarction; Neuropeptide Y; Structural nitric oxide synthase; Inducible nitric oxide synthase; Size of cerebral infarction; NIHSS score

Gingival crevicular fluid and plasma levels of neuropeptide Substance‐P in periodontal health, disease and after nonsurgical therapy

The level of Substance-P in gingival crevicular fluid has been found to correlate with clinical measures of periodontal disease. The present study was designed to assess the relationship between clinical parameters and levels of Substance-P in the gingival crevicular fluid from inflamed gingiva, periodontitis sites and after treatment of periodontitis sites, and to correlate them to the Substance-P levels of plasma. Thirty, age- and gender-matched subjects were divided into three groups (healthy, gingivitis and chronic periodontitis) based on modified gingival index scores and clinical attachment loss. A fourth group consisted of 10 subjects from the periodontitis group, 6-8 wk after initial therapy. Plasma and gingival crevicular fluid samples were collected and quantified for Substance-P using an enzyme immunoassay. The mean concentration of Substance-P, both in gingival crevicular fluid and plasma, was observed to be highest in the periodontitis group (45.13 pg/mL in gingival crevicular fluid and 67.8 pg/mL in plasma) and lowest in the healthy group (6.07 pg/mL in gingival crevicular fluid and below the detection level in plasma). The mean Substance-P concentration in the gingivitis group (11.42 pg/mL in gingival crevicular fluid and 38.8 pg/mL in plasma) and in the after-treatment group (7.58 pg/mL in gingival crevicular fluid and 39.7 pg/mL in plasma) lay between the highest and lowest values. In all groups the gingival crevicular fluid levels showed a statistically significant positive correlation with that of plasma and clinical attachment loss. Substance-P levels were highest in the gingival crevicular fluid from sites with periodontal destruction; however, periodontal treatment resulted in the reduction of Substance-P levels. Gingival crevicular fluid and plasma Substance-P levels showed a positive correlation in all of the groups.

Plasma Neuropeptides in Patients Undergoing Lumbar Discectomy

A prospective analysis of patients with lumbar disc herniation (LDH). To determine the role of neuropeptides as a biochemical signature of pain states in patients with LDH. Increases in the plasma level of neuropeptides have been reported in patients suffering from a variety of painful conditions. However, there is no such report on patients with LDH. From a total of 27 patients with a single-level LDH, blood samples were collected before and 3 weeks after lumbar discectomy. Plasma levels of alpha calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y, and substance P were determined by using enzyme-linked immunosorbent assay. The association or correlation between preoperative concentration of plasma neuropeptides and gender, patients' age, and VAS were analyzed statistically. Also, the concentration of plasma neuropeptides was compared before and after lumbar discectomy. Preoperative plasma levels of CGRP were correlated significantly with the extent of sciatica as determined by VAS. In addition, plasma levels of CGRP and galanin significantly decreased after lumbar discectomy in line with the disappearance of pain symptoms. These findings indicate the role of plasma CGRP and possibly galanin as a systemic neurochemical signature of pain states in patients with LDH.

Modulation of Contractile Function through Neuropeptide Y Receptors during Development of Cardiomyocyte Hypertrophy

Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative contractile effects in cardiomyocytes through Y(1) and Y(2) receptors, respectively. This study tested the hypothesis that NPY receptor-mediated contraction is altered during progression of LVH. Ventricular cardiomyocytes were isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during development (16 weeks), and at established LVH (20 weeks) and age-matched normotensive Wistar Kyoto (WKY) rats. Electrically stimulated (60 V, 0.5 Hz) cell shortening was measured using edge detection and receptor expression determined at mRNA and protein level. The NPY and Y(1) receptor-selective agonist, Leu(31)Pro(34)NPY, stimulated increases in contractile amplitude, which were abolished by the Y(1) receptor-selective antagonist, BIBP3226 [R-N(2)-(diphenyl-acetyl)-N-(4-hydroxyphenyl)methyl-argininamide)], confirming Y(1) receptor involvement. Potencies of both agonists were enhanced in SHR cardiomyocytes at 20 weeks (2300- and 380-fold versus controls). Maximal responses were not attenuated. BIBP3226 unmasked a negative contraction effect of NPY, elicited over the concentration range (10(-12) to 3 x 10(-9) M) in which NPY and PYY(3-36) attenuated the positive contraction effects of isoproterenol, the potencies of which were increased in cardiomyocytes from SHRs at 20 weeks (175- and 145-fold versus controls); maximal responses were not altered. Expression of NPY-Y(1) and NPY-Y(2) receptor mRNAs was decreased (55 and 69%) in left ventricular cardiomyocytes from 20-week-old SHRs versus age-matched WKY rats; parallel decreases (32 and 80%) were observed at protein level. Enhancement of NPY potency, producing (opposing) contractile effects on cardiomyocytes together with unchanged maximal response despite reduced receptor number, enables NPY to contribute to regulating cardiac performance during compensatory LVH.

Plasma levels of neuropeptides in Alzheimer's disease

Background. In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-β peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin–growth hormone (GH) system has been reported.Methods. We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group.Results. No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls.Conclusion. On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.

Effects of Some Kampo Medicines on Plasma Levels of Neuropeptide Y under Venipuncture Stress

Some traditional Chinese herbal (Kampo) medicines have recently been evaluated for their clinical usefulness in stress and depression. These medicines have modulatory effects on the hypothalamic-pituitary-adrenal axis and sympathetic nervous system (SNS). We examined the effects of Rikkunshi-to, Hange-shashin-to, Hange-koboku-to, and Ninjin-to on plasma levels of neuropeptide Y (NPY), which is the representative neurotransmitter of the SNS, under venipuncture stress. Rikkunshi-to and Hange-shashin-to suppressed increases in plasma NPY-immunoreactive substance levels compared with the response to a placebo. In this study, Rikkunshi-to and Hange-shashin-to altered plasma levels of NPY under venipuncture stress. These effects might be beneficial in stress-related diseases and our results suggest that these medicines have clinical pharmacologic activity.

Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity

Plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, but not histamine, were elevated in patients with self-reported multiple chemical sensitivity (sMCS). Exposure to volatile organic compounds (VOC) increased plasma levels of all parameters in these patients, while it had no effect in normal subjects or patients with atopic eczema/dermatitis syndrome (AEDS). Exposure to VOC also enhanced skin wheal responses induced by histamine in patients with sMCS, while it failed to do so in normal or AEDS subjects. These results indicate that exposure to VOC may enhance neurogenic inflammation with concomitant enhancement of histamine-induced responses.

Exposure to road traffic enhances allergic skin wheal responses and increases plasma neuropeptides and neurotrophins in patients with atopic eczema/dermatitis syndrome

The effect of exposure to road traffic was studied by sitting on chairs for 30 min beside a road with heavy wheeled traffic. Exposure to road traffic enhanced allergen-induced, but not histamine-induced, skin wheal responses in 26 patients with atopic eczema/dermatitis syndrome, while it had no effect on skin wheal responses in 26 normal subjects. Exposure to road traffic also increased plasma levels of substance P, vasoactive intestinal peptide, nerve growth factor, and neurotrophin-3 in patients with atopic eczema/dermatitis syndrome, while it had no effect on these plasma parameters in normal subjects. Collectively, exposure to road traffic may aggravate allergic diseases by enhancing allergic responses with concomitant increase in plasma levels of neuropeptides and neurotrophins.

Suckling Reduces Allergic Skin Responses and Plasma Levels of Neuropeptide and Neurotrophin in Lactating Women with Atopic Eczema/Dermatitis Syndrome

Background: Lactation is associated with an inhibited hypothalamic-pituitary-adrenal axis response to physical and psychological stress in women and female rats. However, suckling also improved mood and calmness in nonatopic lactating women. Relaxation by humor reduced allergen-induced skin wheal responses, while various forms of stress enhanced those responses in allergic patients. Moreover, enhancement and reduction in allergen-induced skin wheal responses are associated with up- and down-regulation of plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP), respectively. In addition, plasma levels of SP, VIP and nerve growth factor (NGF), but not neurotrophin-3 (NT-3), are elevated in allergic patients. Therefore, the effects of suckling on allergic responses and plasma levels of neuropeptides and neurotrophins were studied in lactating women with atopic eczema/dermatitis syndrome (AEDS). Methods: Before and after suckling, allergic skin responses to allergens were studied by skin prick test; simultaneously plasma levels of substance P, vasoactive intestinal peptide, nerve growth factor and neurotrophin-3 were measured in lactating women with atopic eczema/dermatitis syndrome. Results: Suckling reduces allergen-induced, but not histamine-induced, skin wheal responses, while holding infants without suckling failed to do so. Suckling also reduced plasma levels of SP, VIP and NGF, but not NT-3 in these patients, while holding infants without suckling failed to do so. Conclusions: These results indicate that suckling reduces allergic responses with a concomitant reduction in plasma levels of SP, VIP and NGF. Collectively, suckling may have some implication in the study of maternal allergy in atopic patients.

Age-dependent levels of plasma neuropeptides in normal children.

Several neuropeptides are secreted in high amounts in pediatric tumors such as neuroblastoma and have been used as markers of residual or recurrent disease. Plasma levels of neuropeptides might be expected to change during development, but have not been determined in normal children. We have obtained fresh plasma from cord blood of six full-term infants and from peripheral blood in 41 healthy children, ages 1 month to 21 years. Levels of six neuropeptides, vasoactive intestinal peptide (VIP), somatostatin, gastrin releasing peptide (GRP), substance P, pancreastatin and neuropeptide Y (NPY) were measured by radioimmunoassay along with insulin-like growth factor-1 (IGF-1) whose plasma levels are known to vary during development. A child with neuroblastoma was treated with the somatostatin analogue, octreotide, and the effect on plasma neuropeptides quantified. Octreotide doses of 2-3 microg/kg daily resulted in a 40-60% decrease in plasma levels of IGF-1, pancreastatin and GRP. These results are the first publication of plasma neuropeptide levels in normal children.