vasoactive-intestinal-peptide and Acute-Disease

While enterocyte secretion is the predominant mechanism considered responsible for secretory diarrhea in response to acute enteric infections, there are several lines of evidence that support alternative mechanisms controlling fluid and electrolyte secretion in diarrhea.. To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea.. Acute infectious diarrheas due to bacterial toxins (e.g., cholera, E. coli heat-stable enterotoxin, C. difficile) and rotavirus are all associated with secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons. The latter secrete acetylcholine (which binds to muscarinic receptors on epithelial cells) and VIP. Involvement of nerves was demonstrated by inhibition of bacterial toxin-induced secretion by hexamethonium (nicotinic), tetrodotoxin (Na(+) channel blocker), and lidocaine (visceral/mucosal afferents). Nicotinic receptors are present on secretomotoneurons and these are activated by release of acetylcholine from enteric interneurons or extrinsic efferent fibers. Specific organisms also modify other mechanisms that may contribute to development of acute diarrhea. Thus, mucin secretion, activation of motor mechanisms, increased mucosal permeability and inhibition of bile acid absorption have been reported in specific types of acute infectious diarrhea.. New therapies targeting neural and transmitter mediation including 5-HT, VIP, NPY, as well as toxin receptors and channels activated during acute infectious diarrhea could usher in a novel approach to enhancing glucose-electrolyte solutions used in the treatment of acute diarrhea.

Topics: Acute Disease; Bacterial Toxins; Dysentery; Enteroendocrine Cells; Humans; Neurons, Afferent; Neuropeptide Y; Serotonin; Vasoactive Intestinal Peptide

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) belong to the same secretin-glucagon superfamily and are present in nerve fibers in dura and skin. Using a model of acute cutaneous pain we explored differences in pain perception and vasomotor responses between PACAP38 and VIP in 16 healthy volunteers in a double-blind, placebo-controlled, crossover study. All participants received intradermal injections of 200 pmol PACAP38, 200 pmol VIP and placebo into the volar forearm. Measurements included pain intensity on a visual analog scale (VAS), blood flow by laser Doppler flowmetry, visual flare and wheal. Pain intensities after PACAP38 and VIP were mild and limited to a short time of about 100 s after injection. The area under the VAS-time curve was larger following PACAP38 (P = 0.004) and VIP (P = 0.01) compared to placebo. We found no statistical difference in pain perception between PACAP38 and VIP. Skin blood flow increase, flare and wheal were larger after both PACAP38 (P = 0.011) and VIP (P = 0.001) compared to placebo. VIP induced a considerably larger increase in skin blood flow, flare and wheal than PACAP38 (P = 0.002). In conclusion, we found that peripheral nociceptive cutaneous responses elicited by PACAP38 and VIP are similar in healthy volunteers. This suggests that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors.

Topics: Acute Disease; Administration, Cutaneous; Adult; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Neurological; Neurogenic Inflammation; Nociceptors; Pain; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide; Young Adult

We aimed to investigate the role of the intestinal neurotransmitters vasoactive intestinal peptide (VIP) and substance P (SP) at different time points in infants with acute intussusception.. Thirty patients who were diagnosed with acute intussusception were enrolled in the study and classified as the experimental group. Another 30 patients with an indirect inguinal hernia who had no intestinal injury were included as the control group. Serum SP and VIP levels at different time points, including pre- and postoperation, were detected by enzyme-linked immunosorbent assay and compared between the two groups.. Serum SP levels in patients with acute intussusception were significantly higher than those in controls. However, with recovery of acute intussusception, SP levels gradually decreased after treatment. Serum VIP levels in patients with acute intussusception were significantly lower than those in controls. However, with recovery of acute intussusception, VIP levels gradually increased after treatment.. SP and VIP levels may have a potential relationship with the pathogenetic process of intussusception.

Topics: Acute Disease; Biomarkers; Case-Control Studies; Female; Follow-Up Studies; Humans; Infant; Intussusception; Male; Prognosis; Retrospective Studies; Substance P; Vasoactive Intestinal Peptide

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

The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all of which may be affected by therapeutic interventions used in the intensive care unit. We measured arterial levels as well as the net cerebral flux of these peptides in patients with ABM, and in healthy volunteers undergoing interventions relevant to intensive care.. Seven patients with severe ABM and sepsis and fifteen healthy volunteers were included after informed consent. The net cerebral fluxes of vasoactive peptides were measured by the Kety-Schmidt technique in ABM patients (baseline study only), as well as in volunteers at baseline, during voluntary hyperventilation, after an intravenous injection of lipopolysaccharide (LPS), and during norepinephrine infusion.. The arterial levels of CGRP, but not of VIP or ET-1, were elevated in patients with ABM, but no net cerebral flux was present. CGRP levels decreased during hyperventilation and after LPS injection. No net cerebral flux of VIP occurred in any group at any time. A cerebral efflux of ET-1, which occurred in volunteers at baseline, was neither present in volunteers after LPS injection nor in patients with ABM.. The arterial concentration of the vasodilatory peptide, CGRP, but of neither VIP nor the vasoconstrictor ET-1, is elevated in patients with ABM and sepsis. A constitutive cerebral output of ET-1 appears to be present in healthy humans, but is abolished after LPS injection.

Topics: Acute Disease; Adult; Aged; Brain; Calcitonin Gene-Related Peptide; Critical Care; Endothelin-1; Female; Humans; Lipopolysaccharides; Male; Meningitis, Bacterial; Middle Aged; Vasoactive Intestinal Peptide

Systemic inhibition of serum CD26/dipeptidylpeptidase (DPP IV) enzymatic activity abrogated acute rejection of pulmonary allografts, whereas organ-specific inhibition ameliorated ischemia/reperfusion injury in syngeneic transplants. Here, we analyze the effect of allograft-specific inhibitor preconditioning on acute rejection in the presence of cyclosporine-based immunosuppressive therapy.. Orthotopic left single lung transplantation (Tx) in rats (LBNF1 to LEWIS). Control (n=5) grafts were flushed with Perfadex alone, whereas treated (n=5) transplants were perfused with Perfadex and AB192, a specific inhibitor of CD26/DPP IV enzymatic activity. All recipients were treated with 2.5 mg of cyclosporine A/kg per day subcutaneously after Tx. Recipients were sacrificed at day 5 after Tx, and oxygenation capacity was measured. In addition, staining for vasoactive intestinal peptide (VIP) and proliferating cell nuclear antigen (PCNA) at explantation (VIP) and at day 5 (VIP, PCNA) was performed with determination of protein levels for PCNA and mRNA for VIP.. Grafts from treated versus controls showed significantly increased oxygenation capacity (P<.008), correlating with significantly less acute rejection (P<.02). PCNA staining and protein expression were significantly lower in perivascular and bronchial epithelial cells (P=.001) in treated versus controls. There was significantly higher staining for VIP at the time of Tx in alveolar macrophages in treated versus controls (P=.001), which was seen up to day 5 post-Tx in both macrophages and respiratory epithelium (P=.001) with elevated mRNA expression for VIP in treated animals.. Perfusion with a specific inhibitor of CD26/DPP IV enzymatic activity was associated with sustained preservation of pulmonary VIP levels, correlating with an amelioration of the acute rejection cascade.

Topics: Acute Disease; Animals; Dipeptidyl-Peptidase IV Inhibitors; Graft Rejection; Lung Transplantation; Male; Organophosphonates; Peroxidase; Proliferating Cell Nuclear Antigen; Proline; Protease Inhibitors; Rats; Rats, Inbred BN; Rats, Inbred Lew; RNA, Messenger; Transplantation Conditioning; Transplantation, Homologous; Vasoactive Intestinal Peptide

T regulatory cells (Tregs) are instrumental in the maintenance of immunological tolerance. Although Treg-based immunotherapy proved successful in preclinical autoimmunity and transplantation, factors involved in the generation of human Ag-specific Tregs are poorly known. In this study, we show that treatment of human CD4+CD25- T cells with the cytokine-like vasoactive intestinal peptide (VIP) during in vitro stimulation induces an anergic FoxP3+CD4+CD25(high) T cell subset displaying potent regulatory activities against allospecific effector T cells, irrespective of the presence of naturally occurring Tregs. VIP-tolerant T cells are characterized by incapability to progress to S phase of cell cycle during stimulation with HLA-disparate APCs by negatively affecting the synthesis of cyclins D3 and E, the activation of cyclin-dependent kinases (cdk)2 and cdk4, and the down-regulation of the cdk inhibitor p27(kip1). VIP interaction with the type 1 VIP receptor and subsequent activation of cAMP/protein kinase A pathway play a major role in all these effects. Moreover, VIP-tolerant T cells protect against acute graft-vs-host disease in a mouse model of allogeneic bone marrow transplantation. The infusion of VIP-tolerant T cells together with the graft significantly reduces the clinical signs and mortality rate typical of the graft-vs-host disease. These effects are mediated by impairing allogeneic haplotype-specific responses of donor CD4+ cells in the transplanted animals. Our results suggest that including alloantigen-specific VIP-generated Tregs may be a valuable tool in therapeutic interventions to promote immunotolerance toward allogeneic grafts and to reduce the need of general immunosuppressive drugs.

Topics: Acute Disease; Animals; Bone Marrow Transplantation; Cell Cycle; Cell Proliferation; Cells, Cultured; Clonal Anergy; Disease Models, Animal; Down-Regulation; Epitopes, T-Lymphocyte; Graft vs Host Disease; Growth Inhibitors; Humans; Isoantigens; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; T-Lymphocytes, Regulatory; 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

To investigate the therapeutic effect and mechanism of electroacupuncture (EA) in treating gastrointestinal disorder in acute pancreatitis (AP) patients.. A total of 94 cases of AP patients were divided into acupuncture group (n=56) and control group (n=38). The severity of AP was evaluated according to APACHE II and Balthazar CT scoring system. EA (4 Hz, 4-6 V) was applied to bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xuanzhong (GB 39), Taichong (LR 3), and Gongsun (SP 4) for 60 min, twice a day, 5 days altogether. Total and segmental colonic transit time (CTT) were determined by using ingestion of radiopaque markers (SITZMARKS) according to the modified Metcalf's method, serum motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) contents were assayed using enzyme linked immunosorbent assay (ELISA).. Compared with normal values, total and segmental CTT of AP patients (control group) increased apparently (P < 0.05), especially in right colon, serum MTL and CCK contents in both control and treatment groups on the 1st day decreased considerably (P < 0.05), while serum VIP levels of both control and treatment groups on the 1st day increased markedly (P < 0.05). In comparison with control group, total and segmental CTT of treatment group decreased significantly (P < 0.05). Auto-comparison of both control and treatment groups showed that serum MTL and CCK contents on day 9 were significantly higher than those on day 1 (P < 0.05), while serum VIP contents on day 9 in these two groups were both obviously lower than those on day 1 (P < 0.05). No significant differences were found between treatment group and control group in serum MTL, CCK and VIP levels on the 9th day after the treatment (P > 0.05).. Acupuncture is able to enhance the gastrointestinal dynamics, improve its motor activity.

Topics: Acute Disease; Adult; Aged; Cholecystokinin; Electroacupuncture; Female; Gastrointestinal Transit; Humans; Male; Middle Aged; Motilin; Pancreatitis; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) exerts a broad range of biologic actions that may include modulation of hepatic granuloma formation. This study aimed to investigate the effect of VIP administration on the course of acute murine schistosomiasis mansoni. Mice were infected each with 40 Schistosoma (S.) mansoni cercariae and injected intraperitoneally with VIP at a total dose of 1mug/kg body weight. VIP treatment was very effective in diminishing worm fecundity, hepatic granuloma size and number by about 54%, 75% and 51%, respectively, and reducing liver collagen content. Serum level of interleukin (IL)-10 was increased, while level of IL-12 and tumor necrosis factor (TNF)-alpha were decreased as a result of VIP administration. Carbohydrate antigen 19.9 (CA 19.9) induced by S. mansoni infection was decreased with VIP treatment. Activities of hepatic gamma-glutamyl transferase (gamma-GT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in liver tissue homogenate of infected treated mice were increased. These results indicate that suitable administration of exogenous VIP can be effective in ameliorating immunopathologic damage associated with schistosomiasis.

Topics: Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; gamma-Glutamyltransferase; Interleukin-10; Interleukin-12; Liver; Liver Diseases, Parasitic; Liver Extracts; Male; Mice; Schistosoma mansoni; Schistosomiasis mansoni; Swine; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide; Vasodilator Agents

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) that induce the generation/activation of regulatory T (Tr) cells for the treatment of acute GVHD following allogeneic BMT has been recently established. Therefore, the identification of factors that contribute to the development of tolerogenic DCs is highly relevant. We report on the use of the known immunosuppressive neuropeptide, the vasoactive intestinal peptide (VIP), as a new approach to induce tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated in the presence of VIP impair allogeneic haplotype-specific responses of donor CD4(+) cells in mice given transplants by inducing the generation of Tr cells in the graft. VIP-induced tolerogenic DCs did not abrogate the graft-versus-leukemia response presumably by not affecting the cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DCs in future therapeutic regimens may minimize the dependence on nonspecific immunosuppressive drugs used currently as antirejection therapy, and facilitate the successful transplantation from mismatched donors, by reducing the deleterious consequences of acute GVHD and extending the applicability of BMT.

Topics: Acute Disease; Animals; Bone Marrow Transplantation; Dendritic Cells; Female; Graft vs Host Disease; Graft vs Tumor Effect; Immune Tolerance; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; T-Lymphocytes, Regulatory; Transplantation, Homologous; Vasoactive Intestinal Peptide

To investigate the effect of treatment with several vasodilatory substance on the changes in mean arterial pressure (MAP) of severe acute pancreatitis.. Pancreatitis was induced in rats by 5% sodium taurocholate retrograde infusion through the pancreatic duct, which produces a significant decrease in arterial blood pressure.. Three hours after the induction of pancreatitis, a fall of approximately 25 mm Hg in MAP was observed, with no changes of MAP in untreated controls. The administration of the nitric oxide synthesis inhibitor, N-nitro-L-arginine methyl ester (25 mg/kg), previously to the induction of pancreatitis, produced a marked fall in MAP leading to the death of all the animals. When several vasodilatory substances, S-nitroso-N-acetylpenicillamine (200 microg x kg x h), calcitonin gene-related peptide (10 microg/kg), and vasoactive intestinal polypeptide (8 microg x kg x h) were administered previously to the induction of pancreatitis, the MAP fall induced by pancreatitis was not observed. The improvement of physiological conditions observed in vasodilator-treated animals is in agreement with histological data, which show only minor structural changes in the pancreas from these animals, in contrast with the severe alterations observed in untreated pancreatitic rats.. : Vasodilation confers protection against the systemic circulatory derangement derived from the development of severe acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Blood Pressure; Calcitonin Gene-Related Peptide; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pancreatitis; Penicillamine; Rats; Rats, Wistar; Shock; Vasoactive Intestinal Peptide; Vasodilator Agents

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) with potent immunoregulatory properties by inducing the generation/activation of regulatory T cells (Tr) for the treatment of acute GVHD following allogeneic BMT has been recently established. Here we report the use of the known immunosuppressive neuropeptide, vasoactive intestinal polypeptide (VIP), as a new approach to inducing tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated with VIP impair allogeneic haplotype-specific responses of donor CD4+ T cells in transplanted mice by inducing the generation of Tr in the graft. Importantly, VIP-induced tolerogenic DCs did not abrogate the graft versus leukemia response, probably because they do not abrogate cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DC in future therapeutic regimens may facilitate the successful transplantation from mismatched donors, reducing the deleterious consequences of acute GVHD, extending the applicability of BMT.

Topics: Acute Disease; Animals; Bone Marrow Transplantation; Cell Differentiation; Dendritic Cells; Graft vs Host Disease; Leukemia; Mice; Survival Rate; Vasoactive Intestinal Peptide

VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC1-R and VPAC2-R agonist) on acute pancreatitis.. Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC1-R agonist, VPAC2-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-alpha production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC1-R agonist, or VPAC2-R agonist, and the expression of VPAC1-R and VPAC2-R mRNA in monocytes was examined.. VPAC1-R agonist significantly decreased serum amylase, IL-6, and TNF-alpha, whereas VPAC2-R agonist markedly increased serum amylase. Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect. In vitro, VPAC1-R and VPAC2-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC1-R agonist reduced IL-6 levels, whereas VPAC2-R agonist increased IL-6 dose-dependently. VPAC1-R agonist reduced TNF-alpha levels in a dose-dependent manner.. VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC1-R.

Topics: Acute Disease; Amylases; Animals; Ceruletide; Cytokines; Interleukin-10; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Monocytes; Pancreas; Pancreatitis; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; RNA, Messenger; Severity of Illness Index; Spleen; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide

Pituitary adenylate cyclase activating-peptide (PACAP) is a late member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family of brain-gut peptides. It is unknown whether PACAP takes part in the development of acute pancreatitis and whether PACAP or its antagonists can be used to suppress the progression of acute pancreatitis. We investigated the actions of PACAP and its receptor antagonists in acute pancreatitis on rats.. Acute pancreatitis was induced in rats with caerulein or 3.5% sodium taurocholate. The rats were continuously infused with 5-30 microg/kg PACAP via jugular vein within the first 90 min, while 10-100 microg/kg PACAP6-27 and (4-Cl-D-Phe6, Leu17) VIP (PACAP receptor antagonists) were intravenously infused for 1 h. Biochemical and histopathological assessments were made at 4 h after infusion. Pancreatic and duodenal PACAP concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Chinese ink-perfused pancreas was fixed, sectioned and cleared for counting the functional capillary density.. PACAP augmented caerulein-induced pancreatitis and failed to ameliorate sodium taurocholate-induced pancreatitis. ELISA revealed that relative concentrations of PACAP in pancreas and duodenum were significantly increased in both sodium taurocholate- and caerulein-induced pancreatitis compared with those in normal controls. Unexpectedly, PACAP6-27 and (4-Cl-D-Phe6, Leu17) VIP could induce mild acute pancreatitis and aggravate caerulein-induced pancreatitis with characteristic manifestations of acute hemorrhagic/necrotizing pancreatitis. Functional capillary density of pancreas was interpreted in the context of pancreatic edema, and calibrated functional capillary density (calibrated FCD), which combined measurement of functional capillary density with dry weight/wet weight ratio, was introduced. Hyperemia or congestion, rather than ischemia, characterized pancreatic microcirculatory changes in acute pancreatitis.. PACAP may take part in the pathogenesis of acute pancreatitis in rats. The two PACAP receptor antagonsits might act as partial agonists. Calibrated functional capillary density can reflect pancreatic microcirculatory changes in acute pancreatitis.

Topics: Acute Disease; Animals; Capillaries; Ceruletide; Cholagogues and Choleretics; Disease Models, Animal; Duodenum; Hormone Antagonists; Male; Nerve Growth Factors; Neuropeptides; Neurotransmitter Agents; Pancreas, Exocrine; Pancreatitis; Peptide Fragments; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Taurocholic Acid; Vasoactive Intestinal Peptide

Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. Vasoactive intestinal peptide (VIP) is a neuropeptide with known anti-inflammatory activity. We have demonstrated previously that administration of VIP inhibits leucocyte migration in a murine model of delayed-type hypersensitivity, and anti-inflammatory efficacy is supported by other studies. The aim of this study was to investigate the VIP effects in a murine model of intestinal inflammation. Colitis was induced in BALB/c mice by a 2.5 mg enema of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and the mice were killed on day 7. Mice were administered either a 3-day (therapeutic) or 7-day (prophylactic) constant infusion of VIP by subcutaneously implanted mini-osmotic pumps, or intraperitoneal (i.p.) injection of VIP on alternate days over 7 days. Clinical disease scores, weight changes, histopathology of colon tissues, plasma VIP levels, cytokine levels and chemotaxis of peripheral blood mononuclear cells were evaluated. After administration of TNBS, mice quickly developed severe colitis accompanied by dramatic body weight loss (20% by day 6) and high mortality (30%). Prophylactic treatment using high-dose VIP abrogated leucocyte chemotaxis; however, it failed to ameliorate the weight loss and mortality. Moreover, VIP delivered either by constant infusion or i.p. failed to modify the clinical, histological or cytokine markers of disease. Our studies show that, despite an ability to inhibit chemokine-induced chemotaxis of mononuclear cells, VIP was unable to modulate TNBS-induced colitis. This contrasts with the efficacy of VIP in models of mild inflammatory disease and suggests that VIP is unlikely to provide a useful model for novel anti-IBD therapy.

Topics: Acute Disease; Animals; Chemotaxis, Leukocyte; Colitis; Infusion Pumps, Implantable; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Models, Animal; Treatment Failure; Trinitrobenzenesulfonic Acid; Vasoactive Intestinal Peptide

In many studies, it has been reported that vasoactive intestinal peptide (VIP) may play an important role in modulation of the immunological response. VIP can be produced by immunological cells, and also the receptors for this neuropeptide are present in many of these cells. The aim of our study was to estimate the effects of the administration of exogenous VIP on serum concentrations of proinflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha] and an anti-inflammatory cytokine (IL-10) during lipopolysaccharide (LPS)-induced acute inflammation. We also estimated the influence of VIP on pituitary [FSH, LH, TSH and prolactin (PRL)], thyroid (T3 and T4), adrenal (corticosterone) and gonadal (testosterone) hormones in response to LPS-induced acute inflammation.. Male Wistar-Kyoto rats were divided into four groups, which received, respectively, placebo (0.9% NaCl), LPS, VIP and VIP with LPS. The TNF-alpha and IL-6 serum concentrations were measured after 2 h from the time of the administration of the agents, IL-10 was measured after 4 h, and the pituitary, thyroid, adrenal and gonadal hormone concentrations were measured after 2 and 4 h. Cytokine concentrations were estimated using ELISA tests, and hormone concentrations were measured using RIA tests.. In our experiments, LPS administration dramatically increased serum proinflammatory cytokine concentrations (TNF-alpha and IL-6) after 2 h and the anti-inflammatory cytokine (IL-10) after 4 h, as well as increasing the serum corticosterone concentration (after 2 and 4 h) and LH (after 2 h). LPS application decreased serum concentrations of T3 and TSH (both after 2 h), testosterone (after 2 and 4 h), FSH after 4 h and PRL after 4 h. VIP administration decreased the serum IL-10 concentration after 4 h and T3 concentration after 2 h and increased serum concentrations of FSH and corticosterone after 4 h. VIP administrated simultaneously with LPS decreased the LPS-induced increase in IL-6 and corticosterone concentrations (consecutively after 2 and 4 h). VIP also enhanced LPS-induced thyroid hormone (T3 and T4) suppression after 4 h and testosterone suppression after 4 h.. We conclude that VIP can modulate not only immune responses but also hormonal responses during acute inflammation.

Topics: Acute Disease; Animals; Cytokines; Disease Models, Animal; Down-Regulation; Endocrine System; Gonads; Hypothalamo-Hypophyseal System; Immune System; Immunologic Factors; Inflammation; Lipopolysaccharides; Male; Pituitary Hormones; Pituitary-Adrenal System; Rats; Rats, Inbred WKY; Steroids; Thyroid Gland; Up-Regulation; Vasoactive Intestinal Peptide

Gut-origin bacterial translocation is one of the major causes of pancreatic necrotic tissue infection in patients with severe acute pancreatitis (SAP). The gastrointestinal dysmotility is supposed to be the fundamental event in this process. To test this hypothesis, alteration of colonic transit time (CTT) in patients with acute pancreatitis (AP) was investigated. In order to evaluate the possible mechanisms involved in gastrointestinal dysmotility, changes of serum motilin (MTL), cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in patients with AP were also measured.. Twenty-four non-consecutive patients with AP and 25 controls were included in this study. The diagnosis of AP was based upon clinical features, biochemical indices and radiological investigation. The severity of AP at admission was evaluated according to the APACHE-II and Balthazar computed tomography (CT) scoring system. Total and segmental CTT in patients with AP and in controls were determined by ingestion of radiopaque markers (Sitzmarks(R)) according to the modified Metcalf's method. Meanwhile, serum MTL and CCK were assessed using radioimmunoassay (RIA), and serum VIP was measured by using ELISA in this study.. Compared to the controls, the total CTT and segmental CTT (mainly right and left hemicolon) were prolonged significantly in 10 patients with SAP and 14 patients with MAP; P < 0.05. Moreover, the total CTT and segmental CTT were markedly more delayed in patients with SAP than in patients with MAP; P < 0.05. The concentrations of serum MTL and CCK were significantly decreased in both MAP and SAP patients compared with those in controls (P < 0.01). There was no significant differences in serum MTL and CCK levels between the SAP and MAP groups; P > 0.05. In addition, the concentration of serum VIP was increased in AP patients, and it reached statistical significance in patients with SAP (P < 0.05).. In conclusion, gastrointestinal dysmotility often occurred in patients with AP, especially more severely in SAP patients. One of the possible mechanisms might be related to the synergic actions of gut hormones, such as MTL, CCK and VIP.

Topics: Acute Disease; Adult; Cholecystokinin; Colon; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Male; Middle Aged; Motilin; Pancreatitis; Radioimmunoassay; Severity of Illness Index; Vasoactive Intestinal Peptide

Inflammatory chemokines recruit various populations of immune cells that initiate and maintain the inflammatory response against foreign Ags. Although such a response is necessary for the elimination of the Ag, the inflammation has to be eventually resolved in a healthy organism. Neuropeptides such as vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), released after antigenic stimulation, contribute to the termination of an inflammatory response primarily by inhibiting the production of proinflammatory cytokines. Here we investigated the effects of VIP and PACAP on chemokine production. We report that VIP and PACAP inhibit the expression of the macrophage-derived CXC chemokines macrophage inflammatory protein-2 and KC (IL-8), and of the CC chemokines MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1, and RANTES in vivo and in vitro. The inhibition of chemokine gene expression correlates with an inhibitory effect of VIP/PACAP on NF-kappaB binding and transactivating activity. The VIP/PACAP inhibition of both chemokine production and of NF-kappaB binding and transactivating activity is mediated through the specific VIP receptor VPAC1, and involves both cAMP-dependent and -independent intracellular pathways. In an in vivo model of acute peritonitis, the inhibition of chemokine production by VIP/PACAP leads to a significant reduction in the recruitment of polymorphonuclear cells, macrophages, and lymphocytes into the peritoneal cavity. These findings support the proposed role of VIP and PACAP as key endogenous anti-inflammatory agents and describe a novel mechanism, i.e., the inhibition of the production of macrophage-derived chemokines.

Topics: Acute Disease; Animals; Cell Line; Cell Migration Inhibition; Cells, Cultured; Chemokines; Chemokines, CC; Chemokines, CXC; Disease Models, Animal; Gene Expression Regulation; Injections, Intraperitoneal; Interleukin-10; Intracellular Fluid; Lipopolysaccharides; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Neuropeptides; NF-kappa B; Peritonitis; Pituitary Adenylate Cyclase-Activating Polypeptide; Protein Binding; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; RNA, Messenger; Signal Transduction; Vasoactive Intestinal Peptide

15-25% of appendices removed from patients with suspected appendicitis appear normal on histological examination. The cause of pain in such patients is unknown. Since the content of neuropeptides seems to be altered in chronic inflammation, we investigated possible changes in peptidergic innervation for substance P (SP), vasoactive intestinal peptide (VIP), and growth-associated protein-43 (GAP-43).. Appendices classified as showing acute appendicitis, non-acute appendicitis (clinical signs of acute appendicitis, but histologically not inflamed), or normal were processed for SP, VIP, and GAP-43 immunocytochemistry. The density of SP immunostaining was assessed by digitised morphometry.. 31 appendix specimens were studied (16 acute, 15 non-acute). 16 specimens were used as controls. Expression of GAP-43 was increased in the non-acute appendices. We observed larger amounts of SP-immunoreactive and VIP-immunoreactive nerves in the mucosal layer of the appendix in patients with non-acute appendicitis than in controls and patients with acute appendicitis (mean % area SP-immunoreactive 0.0496 [SD 0.0113] non-acute, 0.0221 [0.0049] acute, 0.0229 [0.0068] controls). In addition, a close spatial relation between SP-immunoreactive and VIP-immunoreactive nerve fibres and lymphoid cells was detected in the outer zone of lymph follicles.. Neuroproliferation in the appendix, in association with an increase in neurotransmitters SP and VIP, may be involved in the pathophysiology of acute right abdominal pain in the absence of an acute inflammation of the appendix. Our data, together with increasing knowledge about the way in which the nervous system and immune cells interact, suggest that neuroimmune appendicitis is a distinct pathological entity.

Topics: Abdominal Pain; Acute Disease; Adolescent; Adult; Aged; Appendectomy; Appendicitis; Appendix; Diagnosis, Differential; Enteric Nervous System; Female; GAP-43 Protein; Humans; Immunoenzyme Techniques; Lymphoid Tissue; Male; Middle Aged; Neuronal Plasticity; Prospective Studies; Substance P; Vasoactive Intestinal Peptide

Hepatic porphyrias are characterized by neurological symptoms manifested by abdominal pain, neuropathies and mental aberrations. Porphyrins are ubiquitous and essential biochemical constituents of living beings acting as mediators of oxidation reaction in the metabolism of the steroid, drugs, environmental chemicals or as a mean of exchanging gases, such as oxygen and carbon dioxide between the environment and the tissue of the body using endogenous polypeptide properties. The different porphyrins arising from the arrangement of normal heme synthesis are characterized by an accumulation and excretion of specific intermediate porphyrins and/or of precursors exerting toxic effect, initiating cascades of generations of polypeptides, neurotransmitters and gut-brain axis peptide responsible for the symptoms of clinical status. We studied polypeptide levels in 27 patients (19 females, 8 males) presenting acute attack of hepatic porphyria: 2 with ALA dehydratase-deficient porphyria; 9 with acute intermittent porphyria; 12 with porphyria cutanea tarda and 4 with variegate porphyria. During acute attacks of porphyria, polypeptides were found to be constantly increased: vasoactive intestinal polypeptide (VIP); neurotensin (NT); substance P; pancreatic polypeptide; gastrin-releasing peptide; gastrin and motilin. Administration of the somatostatin (antagonizing polypeptide), which was undetectable or low before treatment, apparently alleviated the acute symptomatology. Elevated levels of polypeptides, at least partly, contribute to appearance of acute symptoms in porphyria patients.

Topics: Acute Disease; Adolescent; Adult; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Peptides; Plasmapheresis; Porphyrias, Hepatic; Porphyrins; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory cells. Their widespread distribution and physiological effects suggest that they may play important roles in asthma. We investigated whether, during an exacerbation of asthma, patients displayed changes in plasma levels of the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25 adult patients attending the emergency ward with an exacerbation of asthma was sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY-like immunoreactivity (-LI) were determined by immunoassay, and the results obtained were compared with findings in 21 healthy controls. The mean plasma levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1), SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1, respectively). A relationship was seen between the reversibility of obstruction, expressed as improvement of peak expiratory flow upon treatment, and the neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and CGRP-LI in particular, may therefore be employed as predictors of responsiveness to bronchodilatory therapy.

Topics: Acute Disease; Asthma; Bronchodilator Agents; Female; Humans; Male; Middle Aged; Neuropeptides; Radioimmunoassay; Vasoactive Intestinal Peptide

To elucidate the possible role of vasoactive intestinal peptide (VIP) in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 ml 96% ethanol with or without intravenous or intraperitoneal coadministration of VIP (1 nmol/liter to 1 mumol/liter/100 g). VIP was found to double the mean lesion area when compared with that induced by ethanol alone (P < 0.05), an effect that was prevented by VIP antagonist (1 mumol/liter/100 g). A substance P antagonist (1 mumol/liter/100 g) also reduced the extent of gastric damage induced by coadministration of VIP and ethanol. VIP antagonist or substance P antagonist significantly reduced ethanol-induced gastric mucosal damage. Gastric mucosal levels of LTB4, LTC4, VIP, and substance P were significantly increased in ethanol-treated rats as compared with saline-treated animals (P < 0.05). The augmentation of ethanol-induced damage by VIP was associated with increased gastric mucosal levels of LTB4. In VIP-treated rats, gastric mucosal levels of substance P were found to be significantly increased compared with control rats (P < 0.05). Administration of VIP to pyloric-ligated rats significantly increased gastric acid output and blood pepsinogen A levels as compared with saline treated rats (P < 0.05). Ketotifen, a mast cell stabilizer (100 micrograms/100 g), administered orally 30 min before damage induction by ethanol, with or without VIP, totally abolished the damage of the surface epithelium of the entire gastric mucosa and significantly reduced the mucosal levels of LTC4 and LTB4 (P < 0.05). It is suggested that VIP is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Drug Interactions; Ethanol; Gastric Mucosa; Ketotifen; Leukotrienes; Male; Rats; Stomach Diseases; Substance P; Vasoactive Intestinal Peptide

A study was made with different doses of cerulein (2, 4, 10 and 20 micrograms/kg) administered subcutaneously to rats by four injections at intervals of 1 hr; the aim of this work was to study exocrine pancreatic secretion of the rat under cerulein-induced acute pancreatitis, analyzing enzyme and hydroelectrolyte secretion of pancreatic juice. A further aim was to study the relationship between the dose of cerulein and the plasma levels of peptides controlling hydroelectrolyte secretion of the pancreas, like secretin and vasoactive intestinal peptide (VIP). At the lowest dose schedule, the amounts of total protein and enzymes (amylase and trypsin) in pancreatic juice decreased significantly, plasma amylase increased, and the pancreas became edematous. Higher doses magnified these effects. By contrast, ductular function (flow and HCO3-) was well preserved in cerulein-treated rats, and this was probably due to the significant increase in plasma levels of immunoreactive secretin whereas VIP levels were unchanged. The secretin released by treatment with cerulein is able to palliate the lack of flow from acinar origin that is affected in the process of acute pancreatitis, being a beneficial response to the cerulein treatment.

Topics: Acute Disease; Amylases; Animals; Ceruletide; Drug Administration Schedule; Injections, Subcutaneous; Male; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Reproducibility of Results; Secretin; Vasoactive Intestinal Peptide

Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase cAMP levels: isoproterenol, terbutaline, theophylline, and prostacyclin, was found to reduce the severity of lung injury in animal models. We have investigated the possible modulation of HCl-induced pulmonary edema in rats by VIP, a lung neuropeptide with potent vasodilator and cAMP-producing properties. The lungs of rats were perfused in situ at 10 ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume (6.5 ml/kg). Peak airway pressure (PAW), mean pulmonary arterial pressure (PPA) were measured throughout the experiment, and wet to dry lung weight ratio (W/D), afterwards. All animals were observed for one hour. In 6 rats receiving HCl only, 0.2 N-HCl was instilled intratracheally at 2 ml/kg. Four rats received 2 ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1 micrograms/kg/min, beginning 10 minutes before HCl and for the rest of the experiment. Another 6 rats were pretreated with atrial natriuretic peptide (ANP, atriopeptin II) just like the VIP group. Lungs of saline control animals showed little or no chage in PAW or PPA. With HCl alone, PAW increased immediately and continued to rise for the rest of the hour, reaching 500% of basal value at 30 minutes. PPA increased by 68% and W/D by 74% compared to saline-instilled lungs. In the VIP + HCl group, all abnormalities were significantly reduced relative to the HCl group. The rise in PAW was attenuated by 79% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Burns, Chemical; Hydrochloric Acid; In Vitro Techniques; Lung Injury; Male; Pulmonary Edema; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Topics: Acute Disease; Adult; Aged; Blood Glucose; Diarrhea; Female; Food; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Motilin; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

Topics: Acute Disease; Adult; Aged; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Male; Middle Aged; Pancreatic Polypeptide; Pancreatitis; Vasoactive Intestinal Peptide

The quantitative distribution of bombesin- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities was determined by RIA and immunocytochemistry in regions of trachea, bronchus, and whole lung at various stages of human fetal development and in neonates, children, and adults. In addition, these two immunoreactivities were studied in infants that had died of the acute respiratory distress syndrome. The concentration of bombesin-like immunoreactivity in the whole respiratory tract steadily increased during gestation, reaching a plateau at birth. In the lung, the bombesin concentration remained almost unchanged during childhood, but decreased to one tenth in the adult. In neonates with the acute respiratory distress syndrome, there was a significantly lower bombesin content in all regions of the respiratory tract compared to either normal full-term infants or 24- to 28-week-old fetuses. Immunocytochemistry localized bombesin immunoreactivity within mucosal neuroendocrine cells present in the airway epithelium throughout the respiratory tract and particularly in the intrapulmonary airways. The number of cells increased throughout gestation, reflecting the pattern found by RIA, and were greatly decreased in acute respiratory distress syndrome patients. VIP concentrations were much lower than those of bombesin and did not change significantly with gestational age. In contrast to bombesin, VIP was mainly concentrated in the upper respiratory tract. In infants with the respiratory distress syndrome, the VIP content was not different from normal. These results are compatible with the possibility that bombesin-like peptides may have a role in the normal development of the human lung.

Topics: Acute Disease; Adolescent; Adult; Aged; Bombesin; Child; Child, Preschool; Gestational Age; Histocytochemistry; Humans; Immunoassay; Infant; Infant, Newborn; Lung; Middle Aged; Peptides; Respiratory Distress Syndrome, Newborn; Respiratory System; Tissue Distribution; Vasoactive Intestinal Peptide

Topics: Acute Disease; Animals; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Liver Diseases; Pancreatic Polypeptide; Swine; Vasoactive Intestinal Peptide

Topics: Acidosis, Respiratory; Acute Disease; Animals; Dogs; Gastrointestinal Hormones; Hypoxia; Lung; Vasoactive Intestinal Peptide

Topics: Acute Disease; Adolescent; Adult; Duodenal Ulcer; Female; Gastrointestinal Hormones; Hepatitis; Humans; Liver Cirrhosis, Alcoholic; Male; Pancreatitis; Stomach 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