vasoactive-intestinal-peptide and Chronic-Disease

Pulmonary arterial hypertension (PAH) is a rare, progressive disease for which no cure exists. However, improved understanding of underlying pathophysiological mechanisms has led to the development of several effective treatments that improve haemodynamics and functional status.. An overview of emerging pharmacological approaches to the management of PAH is presented.. A Medline search was performed for studies describing novel treatments and potential therapeutic targets relevant to PAH.. Several different treatments that modulate abnormalities in the prostacyclin, endothelin and nitric oxide pathways have shown efficacy in randomised, controlled studies and are now licensed for use for PAH patients with advanced disease. Furthermore, there is now encouraging long-term survival data associated with use of these agents. A number of other targets with therapeutic potential have also been identified, such as serotonin, platelet-derived growth factor and vasoactive intestinal peptide. Recently, strategies involving combinations of different PAH-specific agents have emerged as a promising approach for those failing monotherapy.. The therapeutic options available for PAH has improved considerably in recent years and is likely to expand in the future.

Topics: Antihypertensive Agents; Chronic Disease; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Therapy, Combination; Female; Humans; Hypertension, Pulmonary; Male; Phosphodiesterase 5 Inhibitors; Prognosis; Prostaglandins; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome; Vasoactive Intestinal Peptide

Topics: Adult; Child, Preschool; Chronic Disease; Colectomy; Colon; Colostomy; Constipation; Electric Stimulation Therapy; Enema; Female; Gastrointestinal Motility; Humans; Infant; Male; Manometry; Monitoring, Ambulatory; Multiple Endocrine Neoplasia Type 2b; Neurons; Nitric Oxide Synthase; Proto-Oncogene Proteins c-kit; Substance P; Vasoactive Intestinal Peptide

A literature review was conducted in relation to a case of chronic diarrhea associated with a VIP (vasoactive intestinal polypeptide) producing ganglioneuroblastoma (GNB), in an 18-month old female baby. This is a rare entity characterized by premonitory, persisting diarrhea, causing fluid and electrolyte changes typical of the WDHA syndrome, associating watery diarrhea, hypokalemia, and achlorhydia. Elevated VIP plasma levels are an indication for an echographic and/or CT-scan search for the causal secreting tumor. Although the prognosis of this condition seems favorable, the recommended treatment is surgery. The VIP substance represents an excellent biological monitoring marker. Ganglioneuroblastomas are tumors of the sympathetic nervous system, which, according to Pearse's cell and embryologic theory (1966), have to be linked to the APUD system tumors (paraneuromas). VIP-producing forms are rare in children, and only 29 case studies have been compiled in the literature since 1970, when the VIP substance was discovered. The case reported in this study illustrates the diagnostic problems raised by such lesions, and allows us to confirm VIP's imputability for the occurrence of the chronic diarrhea condition in this child.

Topics: Chronic Disease; Diarrhea, Infantile; Female; Ganglioneuroma; Humans; Infant; Retroperitoneal Neoplasms; Vasoactive Intestinal Peptide

The mechanisms responsible for the abnormalities of gallbladder emptying in patients with chronic acalculous gallbladder disease (AGD) have not been elucidated. This study was designed to determine whether a muscle defect could explain this gallbladder dysfunction.. Gallbladder contraction induced by a continuous intravenous cholecystokinin octapeptide (CCK-8) infusion was determined by ultrasonography in control subjects, patients with AGD, pigment stones, and cholesterol stones. Muscle cells were obtained by enzymatic digestion. (125)I-CCK-8 binding and [(35)S]guanosine triphosphate gamma S (GTP gamma S) binding studies were performed.. In vivo gallbladder contraction induced by CCK-8 was significantly lower in AGD (29.4%) and cholesterol stones (28.8%) than in pigment stones (59.8%) and normal controls (57.8%; P < 0.01). In vitro muscle cell contraction induced by CCK-8 was also lower in AGD than in pigment stones. It remained impaired in AGD after stimulation with the G-protein activators GTP gamma S and AlF(4) and with the second messenger 1,2-dioctanoyl-sn-glycerol. However, GTP gamma S binding induced by CCK-8 and vasoactive intestinal polypeptide and the binding capacity of CCK receptors were not different between AGD and pigment stones.. These findings suggest that there is a good correlation between in vivo and in vitro gallbladder response to CCK-8 in patients with AGD. Unlike those found in cholesterol stones, the muscle defects in AGD appear to reside in the contractile apparatus.

Topics: Cell Membrane; Cholelithiasis; Cholesterol; Chronic Disease; Colic; Diglycerides; Gallbladder; Gallbladder Diseases; Gallbladder Emptying; Guanosine 5'-O-(3-Thiotriphosphate); Humans; In Vitro Techniques; Iodine Radioisotopes; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Smooth; Receptors, Cholecystokinin; Sincalide; Sulfur Radioisotopes; Ultrasonography; Vasoactive Intestinal Peptide

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.

Topics: Adult; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Humans; Intradermal Tests; Male; Microcirculation; Middle Aged; Neurokinin A; Skin; Substance P; Urticaria; Vasoactive Intestinal Peptide

Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models.. To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis.. The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1β, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum.. The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1β, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1.. ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Topics: Animals; Antidepressive Agents; Behavior, Animal; Biogenic Monoamines; Brain; Chronic Disease; Cytokines; Depression; Drugs, Chinese Herbal; Gastrins; Gastrointestinal Transit; Glucagon-Like Peptide 1; Intestine, Small; Male; Motilin; Rats, Sprague-Dawley; Stress, Psychological; Substance P; Vasoactive Intestinal Peptide

Chronic pelvic pain (CPP) causes compromised the quality of life in women with endometriosis and is often attributed to local inflammation and ingrowth of nerve fibers. In this pilot study, we aimed to investigate whether the inflammation-related vasoactive intestinal peptide (VIP) and interleukin (IL)-6 were increased in affected patients.. Endometrial and endometriotic tissue biopsy specimens, and serum and peritoneal fluid (PF) samples, were obtained from 85 endometriosis patients and 53 controls. VIP and IL-6 analysis and measurement of microvessel density in tissue were performed using immunohistochemistry, Western blotting, RT-qPCR, and ELISA.. Compared with controls, VIP transcript and protein levels were increased in endometrium from endometriosis patients and further elevated in patients with CPP. In addition, microvessel density, a measurement of angiogenic activity, was increased in the endometrium and in endometriosis lesions in the same subset of patients. Serum and PF levels of VIP and IL-6 were higher in women with endometriosis and CPP compared with endometriosis patients who reported no chronic pain.. Vasoactive intestinal peptide is upregulated in endometriosis patients reporting chronic pain. Increased microvessel density in tissue and peritoneal fluid concentrations of IL-6 indicate an elevated inflammation in the pelvic microenvironment of these patients.

Topics: Adult; Ascitic Fluid; Chronic Disease; Endometriosis; Endometrium; Female; Humans; Inflammation; Interleukin-6; Microvessels; Pelvic Pain; Pilot Projects; Quality of Life; Vasoactive Intestinal Peptide

To investigate the roles of vasoactive intestinal peptides (VIPs) in regulating the morphology and F-actin distribution of Schlemm's canal (SC) of rat eyes.. Chronic intraocular pressure (IOP) hypertension models with episcleral venous cauterization (EVC) were treated with topical VIP or PG99-465 (vasoactive intestinal peptide receptors 2 [VPAC2] antagonist). IOPs were measured with Tono-Pen, and the SC parameters, including the cross-section area, circumference, and length, were statistically evaluated by hematoxylin-eosin and CD31 immunohistochemical staining. Immunofluorescence was performed to detect the distribution of F-actin in the SC. Moreover, the distribution of filamentous actin (F-actin) and globular actin (G-actin) in human umbilical vein endothelial cells (HUVECs) was studied under a pressure system by immunofluorescence and Western blotting.. Increased expressions of VIP and VPAC2 receptors, as well as a disordered distribution of F-actin were found in SC endothelial cells (SCEs) in the EVC model. Moreover, topical VIP maintained the normal distribution of F-actin in SCEs, expanded the collapsed SC, and induced a significant decrease in IOP in the EVC model. In in vitro HUVECs, the F-actin/G-actin ratio increased significantly under stress stimulation for 30 minutes. A total of 50 μM VIP helped maintain the normal F-actin/G-actin ratio of HUVECs against stress stimulation.. VIP regulates the distribution of F-actin in SCEs via the VPAC2 receptor in order to induce a decrease in IOP. VIP may represent a new target for antiglaucoma drugs.

Topics: Actins; Animals; Blotting, Western; Chronic Disease; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Human Umbilical Vein Endothelial Cells; Humans; Intraocular Pressure; Limbus Corneae; Male; Ocular Hypertension; Rats; Rats, Sprague-Dawley; Receptors, Vasoactive Intestinal Peptide, Type II; Tonometry, Ocular; Trabecular Meshwork; Vasoactive Intestinal Peptide

Influence of chronic hyperglycemia on chemical coding of enteric neurons in stomach using pig as a model for human diabetic complications.. In the control group in the myenteric ganglia (MG) of the corpus we have noted 22.28% ± 1.19% of nNOS positive neurons, while in diabetic group we have found 40.74% ± 2.22% of nNOS immunoreactive perikarya (increase by 82.85 %). In turn in the pylorus we have observed 15.91% ± 0.58% nNOS containing neurons in control animals and 35.38% ± 1.54% in the diabetes group (increase by 122.37%). In the MG of the antrum and submucosal ganglion (SG) in the corpus hyperglycemia did not cause statistically significant changes. With regard to VIP-positive cell bodies in the antrum MG in the control animals we have noted 18.38 ± 1.39% and 40.74% ± 1.77% in the experimental group (increase by 121.65%). While in the corpus we have observed 23.20% ± 0.23% in the control and 30.93% ± 0.86% in the diabetes group (increase by 33.31%). In turn in the pylorus VIP positive cells bodies constituted 23.64% ± 1.56% in the control group and 31.20% ± 1.10% in the experimental group (increase by 31.97%). In the submucosal ganglion in the corpus we have noted 43.61% ± 1.06% in the control animals and 37.00% ± 1.77% in the experimental group (decrease by 15.15%). Expression of GAL-positive perikarya showed statistically significant changes only in the MG of the antrum and pylorus. In the antrum GAL positive perykarya constituted 26.53% ± 1.52% in the control and 36.67% ± 1.02% in the experimental animals (increase by 38.22%). While in the pylorus GAL positive neurons in the control group constituted 16.32% ± 0.92% and 17.99% ± 0.38% in the experimental animals (increase by 10.23%).. Our results support the hypothesis that in the course of diabetes, long term episodes of high glucose serum level may influence the chemical phenotyping of enteric neurons.

Topics: Animals; Biomarkers; Chronic Disease; Diabetes Mellitus, Experimental; Fluorescent Antibody Technique; Galanin; Gastric Emptying; Humans; Hyperglycemia; Myenteric Plexus; Neuronal Plasticity; Neurons; Nitric Oxide Synthase Type I; Stomach; Streptozocin; Sus scrofa; Swine; Vasoactive Intestinal Peptide

Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.. Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed.. Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05).. Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.

Topics: Adult; Aged; Aged, 80 and over; Cholinergic Neurons; Chronic Disease; Constipation; Down-Regulation; Female; Gastrointestinal Transit; Humans; Male; Manometry; Middle Aged; Neurons; Parkinson Disease; Rectal Diseases; RNA, Messenger; Submucous Plexus; Vasoactive Intestinal Peptide

Intestinal epithelial secretion is coordinated by the submucosal plexus (SMP). Chemical mediators from SMP regulate the immunobiological response and direct actions against infectious agents. Toxoplasma gondii is a worldwide parasite that causes toxoplasmosis. This study aimed to determine the effects of chronic infection with T. gondii on the morphometry of the mucosa and the submucosal enteric neurons in the proximal colon of rats. Male adult rats were distributed into a control group (n = 10) and an infected group (n = 10). Infected rats received orally 500 oocysts of T. gondii (ME-49). After 36 days, the rats were euthanized and samples of the proximal colon were processed for histology to evaluate mucosal thickness in sections. Whole mounts were stained with methylene blue and subjected to immunohistochemistry to detect vasoactive intestinal polypeptide. The total number of submucosal neurons decreased by 16.20%. Vasoactive intestinal polypeptide-immunoreactive neurons increased by 26.95%. Intraepithelial lymphocytes increased by 62.86% and sulfomucin-producing goblet cells decreased by 22.87%. Crypt depth was greater by 43.02%. It was concluded that chronic infection with T. gondii induced death and hypertrophy in the remaining submucosal enteric neurons and damage to the colonic mucosa of rats.

Topics: Animals; Antibodies, Protozoan; Azure Stains; Cats; Cell Death; Chronic Disease; Colon; Coloring Agents; Gastrointestinal Agents; Goblet Cells; Immunoglobulin G; Intestinal Mucosa; Lymphocytes; Male; Mice; Myenteric Plexus; Neurons; Random Allocation; Rats; Rats, Wistar; Submucous Plexus; Toxoplasma; Toxoplasmosis, Animal; Vasoactive Intestinal Peptide

The aim of this article is to determine vasoactive intestinal peptide (VIP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM).. Women older than 17 and diagnosed as CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. VIP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack, the patients having taken no symptomatic medication the day before. For ethical reasons, preventives were not stopped.. We assessed plasma samples from 119 women with CM, 33 healthy women, 51 matched women with EM and 18 patients (16 males) with cluster headache matched for age. VIP levels were significantly increased in CM (165.1 pg/ml) as compared to control healthy women (88.5 pg/ml) and episodic cluster headache patients (101.1 pg/ml). VIP levels in EM (134.9 pg/ml) were significantly higher compared to controls and numerically lower than those of CM. Thresholds of 71.8 and 164.5 pg/ml optimized the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. Variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventive treatment did not significantly influence VIP levels.. Increased interictal VIP level measured in peripheral blood could be a biomarker helping in CM diagnosis, though it does not clearly differentiate between EM and CM.

Topics: Adolescent; Adult; Area Under Curve; Biomarkers; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Middle Aged; Migraine Disorders; Parasympathetic Nervous System; ROC Curve; Vasoactive Intestinal Peptide; Young Adult

Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic migraine (CM). Its precise mechanism of action, however, is unknown.. To analyze a potential relationship between calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels and response to onabotA in CM.. Adult patients with CM were recruited. Matched healthy subjects with no headache history served as controls. CGRP and VIP levels were determined in samples obtained from the right antecubital vein by ELISA outside of a migraine attack and having taken no symptomatic medication prior to treatment with onabotA. OnabotA was administered according to the PREEMPT protocol every 12 weeks for at least two treatment cycles. A patient was considered as a moderate responder when both: (1) moderate-severe headache episodes were reduced by between 33 and 66%; (2) subjective benefit in a visual scale of 0-100 was recorded by the patient of between 33-66%. Patients were considered as excellent responders when both items improved >66%. Those without improvement of at least one-third in the two items were considered as nonresponders.. We assessed plasma samples from 81 patients with CM and 33 healthy controls. CGRP and VIP levels were significantly increased in CM population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. For CGRP, a threshold of 72 pg/mL positively correlated with 95% of nonresponders. The probability of being a responder to onabotA was 28 times higher in patients with a CGRP level above the threshold of 72 pg/mL. Even though the sensitivity for the calculated threshold for VIP was poor, the probability that CM patients with low CGRP levels will respond to onabotA was significantly higher in those patients with high VIP levels.. Interictal CGRP and, to a lesser degree, VIP levels measured in peripheral blood are of great help in predicting response to onabotA.

Topics: Adult; Biomarkers; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Middle Aged; Migraine Disorders; Neuromuscular Agents; Sensitivity and Specificity; Treatment Outcome; Vasoactive Intestinal Peptide; Young Adult

Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.. We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs.. MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca(2+) influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays.. The number of MrgX2(+) skin MCs and the percentage of MrgX2(+) MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2.. MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU.

Topics: Adult; Aged; Aged, 80 and over; Cells, Cultured; Chronic Disease; Eosinophil Granule Proteins; Female; Humans; Male; Mast Cells; Middle Aged; Molecular Targeted Therapy; Nerve Tissue Proteins; Protein Binding; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Skin; Skin Tests; Substance P; Up-Regulation; Urticaria; Vasoactive Intestinal Peptide; Young Adult

H1-receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post-treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti-inflammatory properties of cetirizine.

Topics: Adolescent; Adult; Calcitonin Gene-Related Peptide; Cetirizine; Chronic Disease; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Nerve Growth Factor; Neuropeptide Y; Neuropeptides; Stem Cell Factor; Substance P; Urticaria; Vasoactive Intestinal Peptide; Young Adult

The term "neurogenic appendicopathy" has been used for patients operated on for acute appendicitis with their appendices lacking signs of acute inflammation. The aim of this retrospective study was to clarify the presence of potential neurogenic appendicopathies, analyzing patients' clinical symptoms and their corresponding appendiceal specimens.. One hundred twenty-one patients were identified showing a histological diagnosis of chronic appendicitis. Eventually, 40 patients qualified for the potential diagnosis "neurogenic appendicopathy." Appendix specimens were immunohistochemically examined for the expression of S-100, vasoactive intestinal polypeptide (VIP), and substance P. Controls consisted of 110 patients with acute appendicitis and 120 patients following appendectomies operated on for other reasons.. Eventually, 40 of 120 patients qualified for the potential diagnosis "neurogenic appendicopathy." Compared to patients with acute appendicitis, there was only little difference in clinical symptoms. Histologically, neuromas, thought of being characteristic of neurogenic appendicopathy, were demonstrated significantly more often in the control group (p = 0.01). S-100 was significantly more expressed in the appendicopathy group (p = 0.0024), but nearly 50% of control specimens showed an intense staining, too. S-100(+) neurofibers were significantly (p = 0.00122) more often found in the mucosa of appendicopathy specimens, but this was true for only 25% of specimens. VIP was more strongly expressed in control specimens (p = 0.0211). Substance P was of no diagnostic value.. Our study could not confirm the neurogenic origin of appendicopathies. Yet, clinical data strongly suggest the existence of the entity "appendicopathy." Therefore, we suggest removing a macroscopically unaffected appendix in patients with appendicitis-like symptoms if, on laparoscopy, no other cause can be found.

Topics: Acute Disease; Adolescent; Adult; Aged; Appendectomy; Appendicitis; Appendix; Child; Chronic Disease; Female; Humans; Immunohistochemistry; Laparoscopy; Male; Middle Aged; S100 Proteins; Substance P; Vasoactive Intestinal Peptide; Young Adult

This is the first report demonstrating high levels of substance P (SP) that inversely correlate with vasoactive intestinal peptide (VIP) levels in middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Increased SP and decreased VIP levels might play a role in the pathogenesis of chronic OME.. The etiology of OME is multifactorial, and neurogenic inflammation may play a significant role. SP and VIP levels were not evaluated previously in MEEs of children with OME.. Fifty patients aged 2-12 years (mean age 5.24 ± 2.64) were included in the study. MEEs were classified as mucoid or serous based on the gross appearance. SP and VIP levels were determined using ELISA.. High levels of SP were detected in MEEs. In addition SP levels were significantly higher in serous samples (2910.55 ± 307.96 vs 2218.55 ± 262.30 pg/ml). There were also age-dependent changes, such that SP levels were significantly higher in children aged 2-3 years compared with those who were 4-5 and 6-12 years old. VIP levels were undetectable in 30% of patients and the mean level of VIP was 50.91 ± 16.01 pg/ml in serous middle ear effusions and 54.86 ± 15.91 pg/ml in mucoid MEEs.

Topics: Age Factors; Biomarkers; Child; Child, Preschool; Chronic Disease; Cohort Studies; Disease Progression; Female; Humans; Male; Otitis Media with Effusion; Prognosis; Prospective Studies; Recurrence; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Statistics, Nonparametric; Substance P; Vasoactive Intestinal Peptide

Topics: Calcinosis; Catecholamines; Chronic Disease; Colon; Diagnosis, Differential; Diarrhea, Infantile; Failure to Thrive; Feces; Female; Ganglioneuroma; Humans; Infant; Radiography; Spinal Cord Neoplasms; Spine; Vasoactive Intestinal Peptide

To investigate the effect of Helicobacter pylori (H. pylori) infection on neuronal expressions in the stomach and spinal cord of mice so as to explain dyspepsia symptoms in H. pylori infected patients.. C57BL/6 female mice were studied at 2 weeks (acute infection group) and 12 weeks (chronic infection group) after H. pylori inoculation. Histological analyses for gastric inflammation and bacterial colonization were assessed by HE staining and Warthin-Starry staining. Fos, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide expressions (CGRP) were studied by immunohistochemistry.. H. pylori colonization was present mainly in pyloric region, but bacterial density was similar in both infected groups. The intensity of mucosal inflammation and activity was significantly higher in two infected groups than in those in the control group. The degree of mononuclear and polymorphonuclear cell infiltration in proventricular-glandular region and gastric corpus at 12 weeks after H. pylori inoculation was higher than that at 2 weeks after inoculation. The neuronal expressions of fos, VIP, and CGRP in the stomach and spinal cord were significantly more marked in the infected groups than in the control group, but there was no significant difference between two infected groups.. H. pylori infection induced different degrees of gastric mucosal inflammation in the murine model. Both early and chronic infection groups of mice showed enhanced neuronal expressions of fos, VIP and CGRP of stomach and spinal cord and these could form a basis for appearance of functional dyspeptic symptoms in patients with H. pylori infection.

Topics: Acute Disease; Animals; Calcitonin Gene-Related Peptide; Chronic Disease; Disease Models, Animal; Dyspepsia; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; Mice; Neurons; Proto-Oncogene Proteins c-fos; Spinal Cord; Stomach; Vasoactive Intestinal Peptide

Slow transit constipation (STC) affects up to 3% of all children and is an increasingly recognized cause of chronic constipation in children. We conducted a pilot study to investigate whether genes encoding neurotransmitters (TAC1, TAC3, VIP, NOS1) and receptors (TACR1, TACR2, TACR3, KIT) could be responsible for STC.. One hundred seventeen tag single nucleotide polymorphisms (SNPs), distributed among the candidate genes, were selected from HapMap data and genotyped using Sequenom (San Diego, CA) technology in 35 affected families. Evaluation of association was performed by transmission disequilibrium test and multilocus analysis.. Five SNPs (rs3771863, rs4580655, rs11722288, rs4563545, and rs3782221) in the TACR1, TACR3, KIT, and NOS1 genes were found to be potentially associated with STC, although the significance of these results does not withstand correction for multiple testing.. Our data indicate that 5 SNPs in the NOS1, TACR1, TACR3, and KIT genes could be involved in STC, especially rs3771863 in intron 1 of TACR1, which showed the highest association.

Topics: Adolescent; Child; Child, Preschool; Chronic Disease; Constipation; Enteric Nervous System; Female; Gastrointestinal Transit; Genotype; Humans; Linkage Disequilibrium; Male; Neurotransmitter Agents; Nitric Oxide Synthase Type I; Polymorphism, Single Nucleotide; Receptors, Neurotransmitter; Vasoactive Intestinal Peptide

To use radioreceptor analysis for evaluating whether vasoactive intestinal peptide (VIP) receptors are present in chronic periapical lesions and to determine whether differences in its expression are found according to the size of the lesions.. Twelve periapical lesions were obtained from teeth diagnosed with chronic apical periodontitis and indicated for endodontic surgery; they were classified according to the size of the lesion in two groups of six samples (lesion size greater or smaller than 5 mm), and then processed and labelled with (125)I-VIP. Binding sites were identified by (125)I-VIP and standard VIP competition assays. Mann-Whitney's test was used to establish statistically significant differences in the VIP receptor expression between groups.. Vasoactive intestinal peptide receptor expression was found in all periapical lesion samples. There was a statistically significantly higher expression in periapical lesions <5 mm (P < 0.001).. Vasoactive intestinal peptide receptors were expressed in chronic periapical lesions with levels inversely proportional to lesion size.

Topics: Adult; Chronic Disease; Disease Progression; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Periapical Diseases; Periapical Periodontitis; Radiopharmaceuticals; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

Topics: Acclimatization; Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypoxia; Neuropeptide Y; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide

Topics: Animals; Calcitonin Gene-Related Peptide; Carbon Dioxide; Carotid Body; Chronic Disease; Hypercapnia; Hypocapnia; Hypoxia; Neuropeptide Y; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide; Vasodilation

Morphological changes in the rat carotid bodies 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia (10% O2 for 8 weeks) were examined by means of morphometry and immunohistochemistry. The rat carotid bodies after 8 weeks of hypoxic exposure were enlarged several fold with vascular expansion. The carotid bodies 1 and 2 weeks after the termination of 8 weeks of hypoxic exposure were diminished in size, although their diameter remained larger than the normoxic controls. The expanded vasculature in chronically hypoxic carotid bodies returned to the normoxic control state. In the carotid bodies 1 week after the termination of chronic hypoxia, the density of NPY fibers was remarkably increased and that of VIP fibers was dramatically decreased in comparison with the density in chronically hypoxic carotid bodies. In the carotid bodies 2 and 4 weeks after the termination of hypoxia, the density of SP and CGRP fibers was gradually increased. In the carotid bodies 8 weeks after the termination of hypoxia, the appearance of the carotid body returned to a nearly normoxic state, and the density of SP, CGRP, VIP, and NPY fibers also recovered to that of normoxic controls. These results suggest that the morphological changes in the recovering carotid bodies start at a relatively early period after the termination of chronic hypoxia, and a part of these processes may be under the control of peptidergic innervation.

Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypocapnia; Hypoxia; Immunohistochemistry; Nerve Fibers; Neuropeptide Y; Peptide Fragments; Rats; Rats, Wistar; Substance P; Time Factors; Vasoactive Intestinal Peptide

A paraneoplastic syndrome is occasionally the first clinical symptom seen with tumours. We report on two children who initially presented with paraneoplastic syndromes due to ganglioneuroblastomas: the first with severe watery diarrhoea caused by a ganglioneuroma producing vasoactive intestinal peptide, the second with non-treatable constipation, caused by ganglioneuroma-produced anti-neuronal nuclear antibodies.. Either severe diarrhoea or chronic constipation may represent rare paraneoplastic syndromes in ganglioneuroblastomas.

Topics: Adolescent; Adrenal Gland Neoplasms; Chronic Disease; Constipation; Fatal Outcome; Female; Ganglioneuroblastoma; Humans; Infant; Paraneoplastic Syndromes; Vasoactive Intestinal Peptide; Vomiting

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Topics: Adolescent; Adult; Atrophy; Biopsy; Blood Glucose; Chronic Disease; Diabetes Mellitus; Female; Gastrins; Glucagon; Humans; Hyperplasia; Immunohistochemistry; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Polypeptide; Pancreatitis; Vasoactive Intestinal Peptide

To delineate the clinical features and alterations in innervation and substance P (SP) content in spontaneous chronic corneal epithelial defects (SCCED) in dogs and to conduct a preliminary investigation evaluating the efficacy of topical SP, with or without insulin-like growth factor (IGF)-1, in the treatment of this disorder.. Complete ophthalmic examinations, including Cochet-Bonnet aesthesiometry, were performed in 45 canine patients that had spontaneous corneal epithelial defects of at least 3 weeks' duration and with no identifiable cause. Eighteen patients had superficial keratectomies performed, and the corneal nerves were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Relative fiber densities were assessed qualitatively and quantitatively. Corneal epithelial cell and tear SP contents were determined in affected and normal dogs by an enzyme immunoassay. A preliminary open-label treatment trial of topical SP, with and without IGF-1, was conducted in 21 dogs.. The duration of the erosion before admittance into the study was a mean of 9.22 weeks (range, 3-52). The average patient was middle aged (mean, 9.25 +/- 1.85 years [SD]); no sex predisposition of the disease was identified. Boxers, golden retrievers, and keeshonds were overrepresented when compared with the normal hospital population. Corneal sensation was normal. Marked alterations in corneal innervation were identified in affected dogs with abnormal increased SP and calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses identified surrounding the periphery of the epithelial defect. The SP content of epithelial cells surrounding the defect increased, whereas the tear SP content remained unchanged. Of the canine patients treated with SP, with or without IGF-1, 70% to 75% had complete healing of the defect.. This idiopathic spontaneous corneal disease in dogs shares clinical features with chronic epithelial defects in humans. The presence of marked alterations in peptidergic innervation and positive response to topical therapy with SP suggest that SP plays a critical role in corneal wound-healing processes.

Topics: Administration, Topical; Animals; Calcitonin Gene-Related Peptide; Chronic Disease; Corneal Diseases; Dog Diseases; Dogs; Drug Therapy, Combination; Epithelium, Corneal; Female; Fluorophotometry; Immunoenzyme Techniques; Insulin-Like Growth Factor I; Male; Substance P; Thiolester Hydrolases; Trigeminal Nerve; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypoxia; Immunohistochemistry; Neuropeptide Y; Neuropeptides; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide

Previous studies have established short-term variability in the circulating plasma levels of cardiac peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Our aim was to investigate whether such variable patterns could be observed in other vasoactive peptides.. We measured the immunoreactivity of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in peripheral venous plasma collected at 2-min intervals over a 20-min period from patients with chronic cardiac failure (CCF) and from control subjects. In a second study, blood samples were obtained at 2-min intervals from the pulmonary artery, femoral artery and antecubital vein from patients with normal cardiac function while right atrial pressure and heart rate were constant.. Peripheral blood VIP, NPY and ET-1 had peaks and troughs (levels > 2SD from the mean) in both patients and controls, with approximate intervals of 10 min. Levels of CGRP showed little variation. The overall levels [median (range); pmol L-1] of VIP [patients 27 (2.1-85.5); controls 9.8 (0-34)] and NPY [patients 20 (0-110); controls 12 (5-19)] were higher in patients (P < 0.05). Circulating plasma levels of ET-1 and CGRP were about the same in both groups [ET-1: patients 18 (2-84); controls 18 (0-48); CGRP: patients 4 (1-18.5), controls 5.5 (1-15); P = NS]. Levels of CGRP, VIP and ET-1 were similar in the pulmonary and femoral arteries, whereas systemic arterial levels of NPY were higher than in the pulmonary artery.. The data demonstrate marked variability in circulating levels of the neuropeptides studied. In addition, peaks and troughs were observed every 10-15 min from all three vascular beds. If these peptides are secreted in a pulsatile pattern, then interpretations of single measurements should be guarded. Furthermore, this study raises interesting questions about the physiology of hormone secretion in man.

Topics: Aged; Calcitonin Gene-Related Peptide; Chronic Disease; Endothelin-1; Femoral Artery; Heart Failure; Humans; Middle Aged; Neuropeptide Y; Neuropeptides; Pulmonary Artery; Radioimmunoassay; Vasoactive Intestinal Peptide; Veins

The peripheral nervous system was analysed in the oral mucosa of eight patients with oral lichen planus (OLP), five with a lichenoid reaction (LR) and three with mild chronic inflammation (MCI), by morphometric analysis of nerve fibres containing immunoreactive PGP 9.5, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), or C-flanking peptide of neuropeptide Y (CPON). Overall nerve fibre density was higher in OLP (P=0.039) and LR (P=0.026) compared with healthy oral mucosa and was compatible with sprouting and collateral formation. In contrast to the innervation visualized with structural nerve fibre-marker PGP 9.5, the densities of neuropeptide-immunoreactive nerves were low in inflamed tissue. This is consistent with depletion via local release. Retraction and local loss of innervation were found in areas coinciding with the most severe inflammation and basal membrane (BM) damage. Interestingly, LR showed a twenty-eight-fold loss of post-ganglionic CPON-ir sympathetic nerve fibres (P=0.044). In LR, CPON-ir innervation was markedly lower than in OLP. Finally, the pattern of innervation in relation to inflammatory cell infiltrates and tissue structures differed between OLP and LR. In conclusion, the peripheral nervous system is implicated in the immunopathogenesis of lichen planus and lichenoid reactions, with a disorder-specific difference in this involvement.

Topics: Adult; Aged; Analysis of Variance; Basement Membrane; Calcitonin Gene-Related Peptide; Chronic Disease; Humans; Lichen Planus, Oral; Lichenoid Eruptions; Middle Aged; Mouth Diseases; Mouth Mucosa; Nerve Fibers; Nerve Tissue Proteins; Neuropeptide Y; Statistics, Nonparametric; Stomatitis; Substance P; Sympathetic Nervous System; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Sympathetic ganglia in the adult rat contain various populations of nerve cells which demonstrate plasticity with respect to their transmitter phenotype. The plasticity of the neuronal cell bodies and of the small intensely fluorescent cells in the superior cervical and stellate ganglia in response to hypoxia in vivo (10% O2 for seven days) was assessed by studying the expression of catecholamines and vasoactive intestinal peptide. The levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid and vasoactive intestinal peptide immunoreactivity were determined. In addition, the density of the immunohistochemical staining of cells for tyrosine hydroxylase and vasoactive intestinal peptide was evaluated. In the intact superior cervical ganglion, hypoxia increased the dopamine level as well as the density of small intensely fluorescent cells immunolabelled for tyrosine hydroxylase and vasoactive intestinal peptide. In the axotomized ganglion, hypoxia elicited a twofold rise in the level of the vasoactive intestinal peptide as well as enhancing the density of neuronal cell bodies immunostained for this peptide. Thus, the effect of hypoxia on the expression of vasoactive intestinal peptide expression in neurons was dependent on neural interactions. In the intact stellate ganglion, hypoxia alone induced a 1.5-fold increase in the density of neuronal cell bodies immunostained for vasoactive intestinal peptide. Thus, ganglia-specific factors appeared to play a role in determining changes in neuronal phenotype in response to hypoxia. The present study provides evidence for the involvement of dopamine and vasoactive intestinal peptide in ganglionic responses to long-term hypoxia as well as for differential responses by the two ganglionic cell populations, i.e. neuronal cell bodies and small intensely fluorescent cells. Changes in the expression of the vasoactive intestinal peptide during long-term hypoxia may be of energetic, trophic and/or synaptic significance. Hypoxia may be considered to be a vasoactive intestinal peptide-inducing factor in sympathetic ganglia.

Topics: Animals; Catecholamines; Chronic Disease; Hypoxia; Immunohistochemistry; Male; Neuronal Plasticity; Phenotype; Rats; Rats, Sprague-Dawley; Reference Values; Stellate Ganglion; Superior Cervical Ganglion; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The distribution of a tachykinin (substance P) and vasoactive intestinal peptide (VIP) and the number and morphology of the large granular vesicles (LGV) in the myenteric plexus of the colons of mice were investigated. Six of the 12 young, male, Swiss mice studied had been inoculated with the Y strain of Trypanosoma cruzi 2 months previously whereas the others were uninfected controls. Substance P (SP) and VIP were localized by light microscopy, using an immunohistochemical method, and LGV were counted in sections studied by electron microscopy. There were far fewer LGV and less intensely staining varicose VIP- and SP-positive nerve fibres in the infected mice than in the controls. Denervation of the myenteric plexus may decrease the content of tachykinins (TK) and VIP in animals infected with T. cruzi. Such reduction in TK and VIP activity could be related to the disturbances in intestinal motility observed in the chronic phase of Chagas disease.

Topics: Animals; Chagas Disease; Chronic Disease; Colon; Immunohistochemistry; Male; Mice; Microscopy, Electron; Myenteric Plexus; Neurons; Substance P; Vacuoles; Vasoactive Intestinal Peptide

Patients suffering from idiopathic slow-transit chronic constipation have a delayed colonic transit referable to a decrease or loss of propagating contractions. Myogenic and/or neural mechanisms have been implicated in the pathophysiology of this dysfunction and neuronal abnormalities have been described at the ascending, descending and sigmoid colon. The morphology and motile behaviour of the ileocecocolonic region, which in healthy subjects regulates cecum filling and emptying, have never been investigated in such disease. Therefore, we endoscopically ascertained whether a motility impairment was present at these junctional areas and neither spontaneous nor provoked occlusive contractions were found at the cecocolonic junction. Light and electron microscope examination of the entire colon revealed apparently normal features of neurons, smooth muscle cells and interstitial cells of Cajal, while immunohistochemistry and quantitative analysis demonstrated neuronal anomalies at the junctional areas. These anomalies consisted of low total neuron density and significantly few VIP-immunoreactive neurons at the two enteric plexuses, significantly few NOS-immunoreactive neurons at the myenteric plexus and significantly more NOS-immunoreactive neurons at the submucous plexus. These findings exclude a myopathy and demonstrate the existence of a neuropathy. In particular, the presence at the ileocecocolonic region of few VIP- and NO-producing neurons suggests that there might be a reduced VIP and NO production which may result in a compromised relaxation and/or onset of propagating contractions, slowing down bolus transit. The presence at the proximal colon of such an abnormality might explain why left colectomy and/or cecorectal anastomosis are unsuccessful in patients with this disease.

Topics: Adult; Chronic Disease; Colon; Constipation; Endoscopy, Gastrointestinal; Female; Gastrointestinal Motility; Humans; Ileum; Mathematical Computing; Middle Aged; Muscle, Smooth; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Vasoactive Intestinal Peptide

Neuropeptides act on most of the components of the bronchial environment. They influence bronchomotor tone and bronchial vascular caliber and permeability. To investigate the nonadrenergic, noncholinergic system within the airways in asthma and chronic bronchitis, we performed endobronchial biopsies in 16 normal human volunteers, 49 patients with asthma of varying severity, including 16 patients treated with oral corticosteroids, and 13 patients with chronic bronchitis. Frozen sections of biopsies stained with specific antibodies against the neural marker PGP 9.5, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were analyzed for the presence of nerves through indirect immunofluorescence. Nerves were present in most of the biopsies and were found within and below the epithelium and adjacent to smooth muscle, glands, and blood vessels. By comparison with those in normal subjects, the numbers of VIP-immunoreactive nerves were not significantly decreased in patients with asthma and chronic bronchitis, but NPY-immunoreactive nerves were significantly decreased in the smooth muscle of these latter two groups of patients (p < 0.005). There was no correlation between disease severity and the number of nerves found in the biopsies. This study does not confirm previous findings in autopsy material of some defects in sensory and VIP-containing nerves in severe asthma.

Topics: Administration, Oral; Adolescent; Adult; Aged; Asthma; Beclomethasone; Biomarkers; Biopsy; Bronchi; Bronchitis; Bronchoconstriction; Calcitonin Gene-Related Peptide; Capillary Permeability; Chronic Disease; Epithelium; Female; Fluorescent Antibody Technique, Direct; Glucocorticoids; Humans; Male; Middle Aged; Mucous Membrane; Muscle, Smooth; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Prednisone; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide; Vasomotor System

The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P<0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.

Topics: Acetylcholine; Adenosine Triphosphate; Adult; Atropine; Cholinergic Fibers; Chronic Disease; Colon; Constipation; Electric Stimulation; Gastrointestinal Motility; Guanethidine; Humans; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Substance P; Vasoactive Intestinal Peptide

The presence and distribution of neuropeptide-containing nerves within bronchial surgical specimens has been investigated in bronchitic (n = 12) and in nonbronchitic subjects (n = 7). Lung tissue, obtained from patients undergoing thoracotomy for limited lung lesions, was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5) and the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), calcitonin-gene related peptide (CGRP). There were no significant differences between the two groups with respect to the density of PGP 9.5-, SP-, or CGRP-positive nerves in both the locations assessed (smooth muscle layer and glands). The density of VIP-positive nerves was significantly higher in the glands of bronchitic than in nonbronchitic subjects. A negative relationship was found between the presence of airway inflammation, as indexed by mononuclear cell tissue infiltration, and the density of PGP 9.5-positive nerves in both smooth muscle and glands. Likewise, a relationship was found between the smoking history (packs/yr and age of onset of smoking) and the density of VIP-positive nerves in glands. These findings support a role for VIP in the hallmark of chronic bronchitis, i.e., sputum production.

Topics: Adult; Aged; Aged, 80 and over; Bronchi; Bronchitis; Calcitonin Gene-Related Peptide; Chronic Disease; Exocrine Glands; Humans; Immunohistochemistry; Male; Middle Aged; Mucus; Nerve Tissue Proteins; Neurons; Smoking; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Compression-induced changes in the concentration of substance P and VIP (vasoactive intestinal polypeptide), in spinal nerve roots and dorsal root ganglia were studied in an experimental nerve root compression model in pigs.. To analyze by radioimmunoassay the concentration of the neuropeptides substance P and VIP in a model for experimental chronic nerve root compression.. Neuropeptides such as substance P and VIP seem to be involved in the transmission of pain and changes in the levels of these neuropeptides have been described in models where peripheral or spinal nerve injury was induced.. An ameroid constrictor was applied on a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor is gradually reduced. After 1 or 4 weeks, tissue samples were taken from the nerve root cranial to the constrictor and from the dorsal root ganglion for measurement of substance P and VIP concentrations.. There was a statistically significant increase in substance P concentrations in the compressed dorsal root ganglia when compared to the noncompressed dorsal root ganglia at both 1 and 4 weeks. Substance P concentration was also significantly increased in the nerve root after 1 but not after 4 weeks. The VIP levels were not significantly changed in either tissue.. The results of the study indicates an increase in substance P levels in the dorsal root ganglion (after 1 and 4 weeks) and in the nerve root (after 1 week) in a model for chronic nerve root compression in pigs. There were no significant differences in the VIP concentrations. The study thus indicates that changes in substance P are related to experimental chronic nerve root compression.

Topics: Animals; Chronic Disease; Disease Models, Animal; Female; Ganglia, Spinal; Male; Nerve Compression Syndromes; Spinal Nerve Roots; Substance P; Swine; Vasoactive Intestinal Peptide

The vasoactive intestinal peptide (VIP) immunoreactive nerve fibres in the gallbladder from 14 human patients with cholelithiasis was examined by immunohistochemical method. In the chronic cholecystitis, hyperplastic VIP immunoreactive nerves were observed around the hypertrophied muscle bundles, Rokitansky Aschoff Sinus and in the mucosal layer. However, in the acute cholecystitis and gangrenous cholecystitis, reduction or disappearance of VIP nerve fibres was observed. These reductions or disappearances of VIP immunoreactive nerves may secondly result from severe tissue damage. These results suggest that hyperplastic VIP nerves cause gallbladder relaxation, stasis and mucosal fluid unbalance, which may closely correlate to gallstone formation.

Topics: Adult; Aged; Aged, 80 and over; Cholecystitis; Cholelithiasis; Chronic Disease; Female; Gallbladder; Humans; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Vasoactive Intestinal Peptide

Idiopathic chronic constipation has been correlated to neural abnormalities that consist of a reduced number of myenteric plexus neurons and a decreased concentration of VIP-positive nerve fibers within the circular muscle. Recent studies hypothesized the involvement of nitric oxide in motility disorders of the human gut. To date, no information is available on nitric oxide involvement in idiopathic chronic constipation. The density of VIP- and nitric oxide-producing neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide synthase antibodies in five patients with idiopathic chronic constipation. A low total neuron density was found at the myenteric plexus. The density of VIP-positive neurons was low while that of nitric oxide synthase-positive neurons was high at both plexuses. Our data confirm that idiopathic slow-transit chronic constipation is due to abnormal neurogenic factors. The presence of numerous nitric oxide synthase-positive neurons, all along the colon and at both plexuses, supports the hypothesis that an excessive production of nitric oxide may cause the persistent inhibition of contractions.

Topics: Adult; Cell Count; Chronic Disease; Constipation; Enteric Nervous System; Female; Humans; Immunohistochemistry; Neurons; Nitric Oxide Synthase; Vasoactive Intestinal Peptide

The influence of long-term hypoxia on vasoactive intestinal peptide-like immunoreactivity (VIP-LI) in discrete brain areas and peripheral structures was assessed by RIA. Rats were exposed to normobaric hypoxia (10% O2-90% N2) for 14 days. VIP-LI was significantly increased in carotid bodies of hypoxic animals (204% vs. normoxic animals). On the other hand, VIP-LI was decreased in the anterior pituitary (-68%), suprachiasmatic nuclei (-29%) and periventricular nuclei (-26%). No significant variation in VIP-LI was observed in other peripheral structures and discrete brain area studied. These results suggest that long-term hypoxia induces alterations in VIP systems implicated in chemoreception, biological rhythms and neuroendocrine functions.

Topics: Animals; Brain; Carotid Body; Chronic Disease; Ganglia; Hypoxia; Male; Organ Specificity; Pituitary Gland, Anterior; Radioimmunoassay; Rats; Rats, Inbred Strains; Reference Values; Vasoactive Intestinal Peptide

Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity, whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.

Topics: Acetates; Acetic Acid; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Chronic Disease; Male; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Vasoactive Intestinal Peptide; Wound Healing

The distribution and concentration of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats with experimentally induced chronic pancreatitis and of age- and sex-matched controls were investigated. By narrowing the main pancreatic duct between the head and the body to approximately 25% of its normal diameter, we induced within 5 weeks chronic pancreatitis restricted to the body and tail. In control animals, peptide immunoreactive nerves were distributed to the islets, acini, and ducts; the latter were predominantly innervated by fibers immunoreactive for NPY, VIP, or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide immunoreactivities were identified in fibers and ganglion cells, with the exception of CGRP and SP immunostaining, which could be visualized only in fibers. In animals with chronic pancreatitis, the innervation pattern of each peptidergic system was comparable to that described in controls. However, there was a remarkable increase in the density and staining intensity of VIP and NPY immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP and SP also were moderately denser than in controls, whereas those containing GRP immunoreactivity did not show any detectable changes. In addition, a marked increase of the immunostaining for VIP and, to a much lesser extent, for NPY and GRP, was observed in neurites supplying the head of the pancreas, which appeared devoid of histologically detectable pathological alterations. Radioimmunoassay analysis confirmed the immunohistochemical observations. The increased density of distinct peptidergic nerves in the pancreas with induced chronic pancreatitis might be the result of compensatory phenomena in response to the inflammatory process.

Topics: Animals; Calcitonin Gene-Related Peptide; Cats; Chronic Disease; Constriction; Female; Gastrin-Releasing Peptide; Immunohistochemistry; Male; Neuropeptide Y; Neuropeptides; Pancreas; Pancreatic Ducts; Pancreatitis; Peptides; Substance P; Tachykinins; Vasoactive Intestinal Peptide

Gastrin releasing peptide (GRP) is known to stimulate pancreatic enzyme and islet hormone secretion. In the present immunohistochemical study, the localization and distribution of GRP-like immunoreactivity were investigated in the human pancreas using two antisera with different specificities. GRP-like immunoreactivity (GRP-LI) was observed in numerous nerve fibers diffusely distributed to the exocrine pancreas, but was not seen in intrapancreatic nerve cells of normal pancreatic specimens examined. Nerve fibers and terminals with GRP-LI were found in abundance around pancreatic acini and capillaries, with moderate density around ductules and in the walls of arterioles, and a few were seen in islets. This distribution pattern was quite similar to that of vasoactive intestinal polypeptide (VIP)-LI nerve fibers. The study, using the antibody elution method, strongly suggests the co-localization of GRP- and VIP-LIs within a part of VIP-containing nerve fibers. In the chronic pancreatitis specimens, neurons with GRP-LI were frequently found, and > 90% of intrapancreatic nerve cells were VIP-immunoreactive. Immunostainings for GRP and for VIP on serial adjacent sections of intrapancreatic ganglia from chronic pancreatitis specimens suggested the co-localization of the two immunoreactivities in > 70% of intrapancreatic neurons. The present findings may provide a morphological basis for neurotransmitter and/or neuromodulator roles of GRP in the human pancreas.

Topics: Antibody Specificity; Bombesin; Chronic Disease; Gastrin-Releasing Peptide; Humans; Immunoenzyme Techniques; Nerve Fibers; Neurons; Neuropeptides; Pancreas; Pancreatitis; Peptides; Reference Values; Vasoactive Intestinal Peptide

Neurogenic components are probably involved in the pathogenesis of atopic dermatitis (AD) and several neuropeptides have been implicated in the mechanisms underlying this disease. The aim of the present study was to evaluate by radio-immunoassay (RIA), the vasoactive intestinal polypeptide (VIP) and substance P (SP) content in whole-skin homogenates of AD lesions. RIA was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment VIP (22-28) and a polyclonal antiserum directed against SP. VIP levels were markedly increased in lesional AD skin (5.62 +/- 1.25 pmol/g tissue) vis-à-vis controls (0.43 +/- 0.08 pmol/g tissue), whereas SP levels were significantly lower in lesional skin (0.25 +/- 0.03 pmol/g tissue) than in normal skin (0.97 +/- 0.24 pmol/g tissue). The results confirm that VIP and SP are relevant to the pathogenesis of AD and their imbalance might reflect diverse roles of these NP in the modulation of AD lesion.

Topics: Adolescent; Adult; Child; Chronic Disease; Dermatitis, Atopic; Female; Humans; Male; Peptide Fragments; Radioimmunoassay; Skin; Substance P; Vasoactive Intestinal Peptide

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

Topics: Adult; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Humans; Male; Nerve Fibers; Neuropeptide Y; Neuropeptides; Pain; Pancreas; Pancreatitis; Peptide PHI; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Chronic pelvic pain in women is associated with radiological evidence of pelvic venous dilatation and reduced flow, termed 'pelvic congestion'. The aim of this study was to elucidate a possible role in this condition for vasoactive intestinal peptide and calcitonin gene-related peptide, both localized in perivascular nerves in the ovaries and uterus. Healthy volunteers and women with chronic pelvic pain and venous congestion received intravenous infusions of vasoactive intestinal peptide (n = 15), calcitonin gene-related peptide (n = 15) or a bland infusate (n = 7). Changes in the uterovaginal and skin blood flow were assessed by continuous measurement of vaginal, axillary, cheek and hand temperature. During calcitonin gene-related peptide infusion median hand temperature changes were +0.97 degrees C in women with pelvic pain and -0.03 degrees C in healthy volunteers (p < 0.05). There were no differences between groups in hand and cheek temperature responses to vasoactive intestinal peptide infusion. Vasoactive intestinal peptide and calcitonin gene-related peptide appeared to dilate the uterovaginal vasculature in healthy subjects but not in those with pelvic pain. Vasoactive intestinal peptide and calcitonin gene-related peptide did not provoke pain in healthy subjects but in those with pelvic pain, symptoms were significantly exacerbated during calcitonin gene-related peptide infusion but not by vasoactive intestinal peptide. Changes in plasma follicle stimulating hormone, luteinizing hormone and oestradiol during either infusion were not significant. These findings indicate greater sensitivity to calcitonin gene-related peptide in women with pelvic pain and suggest a possible underlying neurovascular disorder.

Topics: Adult; Blood Pressure; Body Temperature; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Humans; Infusions, Intravenous; Pain; Pain Measurement; Pelvis; Vasoactive Intestinal Peptide

By means of radioimmunoassay, the mucosal substance P (SP) and vasoactive intestinal polypeptide (VIP) concentration in distal ileum, transverse colon and sigmoid colon in 30 patients of chronic diarrhea with splenic weakness was determined and compared with that in 28 patients of chronic diarrhea without splenic weakness and in 15 controls without chronic diarrhea. In patients of chronic diarrhea with splenic weakness, the SP contents in the mucosa of distal ileum (120.95 +/- 90.70 pg/mg wet weight) was significantly increased compared with that in controls without diarrhea (47.86 +/- 35.49 pg/mg wet weight) and in chronic diarrhea without splenic weakness (52.50 +/- 42.49 pg/mg wet weight), P less than 0.01 and 0.01 less than P less than 0.05 respectively. The VIP contents of sigmoid mucosa in patients of chronic diarrhea with splenic weakness (510.63 +/- 265.22 pg/mg wet weight) was markedly increased in comparison of that in controls without chronic diarrhea (308.67 +/- 204.49 pg/mg wet weight), 0.01 less than P less than 0.05, and was not significantly augmented compared with that in chronic diarrhea without splenic weakness (398.97 +/- 240.80 pg/mg wet weight), but the tendency of increase was present. Our results suggested that the increased SP and VIP in patients of chronic diarrhea with splenic weakness might be closely related to the symptom of chronic diarrhea. According to the general function of VIP, the authors predicted that VIP might play a more important role in the pathogenetic action of chronic diarrhea with splenic weakness.

Topics: Adult; Chronic Disease; Diarrhea; Female; Humans; Intestinal Mucosa; Male; Splenic Diseases; Substance P; Vasoactive Intestinal Peptide

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Chromatography, Gel; Chronic Disease; Diarrhea; Female; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Radioimmunoassay; Vasoactive Intestinal Peptide

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.

Topics: Adult; Bombesin; Chronic Disease; Colon; Constipation; Enkephalin, Methionine; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Muscle, Smooth; Peptide PHI; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chronic Disease; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Pancreatitis; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

The diagnosis of vasoactive intestinal poly-peptide-secreting tumor (VIPoma) was established in two boys on the basis of watery diarrhea with hypokalemia, elevated plasma levels of vasoactive intestinal polypeptide (VIP) (range of 55-94 pmol/L), and presence of a tumor of the left adrenal gland. Despite celiac angiography, VIP estimation in blood samples taken from different parts of the body, and exploratory laparotomy, localization of the tumor in one child in vivo was unsuccessful. In the other boy, computed tomography revealed a large tumor in the left adrenal gland. Following the removal of the tumor, diarrhea ceased, and 10 days after surgery, the plasma level of VIP was 5 pmol/L. Histologically, the tumors in the two boys were found to be ganglioneuromas. The diagnosis of VIPoma is simple but localization can be very difficult. Surgical removal of VIPoma is often rewarding.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Child; Chronic Disease; Dehydration; Diarrhea; Ganglioneuroma; Humans; Hypokalemia; Male; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Child; Child, Preschool; Chronic Disease; Female; Ganglioneuroma; Hormones, Ectopic; Humans; Male; Retroperitoneal Neoplasms; Vasoactive Intestinal Peptide; Vipoma

This paper describes two children with diarrhea, hypokalemia, and VIP-secreting ganglioneuroblastomas, and includes further evidence that VIP is the cause of the loose stools among patients with such tumors. It suggests that the level of this peptide should be measured in pediatric patients with intractable diarrhea of unknown etiology. Clinicians have long recognized intractable diarrhea as an occasional feature of neuroblastoma, ganglioneuroblastoma or ganglioneuroma. Until recently catecholamine was thought to cause the frequent stools in some patients with these tumors. New radioimmunoassay methods, the identification of new hormones and hormone-like substances, and the discovery that some of the tumors which cause diarrhea secrete Vasoactive Intestinal Peptide (VIP), make it probable that this substance is responsible for the diarrhea in such patients.

Topics: Child, Preschool; Chronic Disease; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Infant; Male; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Celiac Disease; Child, Preschool; Chronic Disease; Cystic Fibrosis; Diagnosis, Differential; Diarrhea; Ganglioneuroma; Gastrointestinal Hormones; Humans; Male; Vasoactive Intestinal Peptide

The neural and hormonal peptide content of rectal biopsy specimens from 10 patients with chronic autonomic failure, 10 patients with chronic gastrointestinal Chagas' disease, and 13 controls was studied with radioimmunoassay and immunocytochemistry. In the patients with Chagas' disease the mean concentrations of rectal vasoactive intestinal polypeptide, enteroglucagon, substance P, and somatostatin were all less than half of those in controls and in patients with chronic autonomic failure. Immunocytochemistry revealed a considerable reduction in the number and immunostaining of the peptide-containing cells and nerves. Concentrations of regulatory peptides in the rectum are thus reduced in association with intrinsic but not extrinsic autonomic neuropathy.

Topics: Autonomic Nervous System; Biopsy; Chagas Disease; Chronic Disease; Gastrointestinal Hormones; Humans; Intestinal Diseases, Parasitic; Nervous System Diseases; Rectum; Somatostatin; Substance P; Vasoactive Intestinal Peptide

The case of an infant who developed refractory watery diarrhea at the age of 2 weeks is described. Diarrhea was secretory in type, stool weight on no oral intake was 400 to 600 gm daily. A vasoactive intestinal peptide (VIP)-producing tumor was suspected. At the age of 7 1/2 months an exploratory laparotomy revealed nonbeta islet cell hyperplasia of the pancreas. VIP levels were elevated in plasma and pancreatic tissue. After 95% pancreatectomy, plasma VIP level dropped to normal. Hypokalemia, described in adult patients with VIP-producing pancreatic tumors and refractory watery diarrhea, was not a significant problem in this infant. This is the first report on the association of refractory watery diarrhea with elevated levels of plasma VIP and pancreatic islet nonbeta cell hyperplasia in the pediatric age group.

Topics: Adenoma, Islet Cell; Chronic Disease; Diagnosis, Differential; Diarrhea, Infantile; Humans; Hyperplasia; Infant, Newborn; Infant, Newborn, Diseases; Islets of Langerhans; Male; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

In animals, the effects of vasoactive intestinal polypeptide (VIP) include peripheral vasodilation, hyperdynamic circulation, hyperglycemia, and hyperventilation. Because these phenomena are noted in patients with cirrhosis, it has been postulated that VIP might be escaping hepatic inactivation and entering the systemic circulatory system and contributing to these abnormalities. The major purpose of this study is to establish whether or not VIP levels are elevated in patients with cirrhosis. Additional goals are to determine if VIP levels are elevated in acute liver disease and in chronic illnesses with secondary liver involvement. The data demonstrate that patients with cirrhosis and those with acute liver disease or chronic illnesses with secondary hepatic involvement have a wide range of VIP levels with mean values significantly above that of normal individuals and patients with chronic illness and no liver involvement.

Topics: Acute Disease; Chronic Disease; Gastrointestinal Hormones; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Neoplasm Metastasis; Vasoactive Intestinal Peptide

Topics: Child, Preschool; Chronic Disease; Diarrhea, Infantile; Ganglioneuroma; Gastrointestinal Hormones; Humans; Male; Thoracic Neoplasms; Vasoactive Intestinal Peptide