Vasoactive intestinal peptide: a potential target for antiviral therapy / 生理学报

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Characteristics of Pruritus according to Morphological Phenotype of Psoriasis and Association with Neuropeptides and Interleukin-31

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.@*METHODS@#Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction.@*RESULTS@#Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05).@*CONCLUSIONS@#ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Differential Innervation of Secretory Coils and Ducts in Human Eccrine Sweat Glands / 中华医学杂志(英文版)

Background@#Previous studies demonstrate that eccrine sweat glands are innervated by both cholinergic and adrenergic nerves. However, it is still unknown whether the secretory coils and ducts of eccrine sweat glands are equally innervated by the sympathetic nerve fibers. To well understand the mechanisms on sweat secretion and reabsorption, the differential innervation of secretory coils and ducts in human eccrine sweat glands was investigated in the study.@*Methods@#From June 2016 to June 2017, six human skins were fixed, paraffin-embedded, and cut into 5 μm-thick sections, followed by costaining for nerve fiber markers protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP), and eccrine sweat gland markers K7, S100P, and K14 by combining standard immunofluorescence with tyramide signal amplification (IF-TSA). Stained sections were observed under the microscope, photographed, and analyzed.@*Results@#The fluorescent signals of PGP 9.5, TH, and VIP were easily visualized, by IF-TSA, as circular patterns surrounding eccrine sweat glands, but only PGP 9.5 could be observed by standard IF. The IF-TSA method is more sensitivity than standard IF in detecting antigens expressed at low levels. PGP 9.5, TH, and VIP appeared primarily surrounding the secretory coils and sparsely surrounding the sweat ducts.@*Conclusion@#Sweat secretion is mainly controlled by autonomic nerves whereas sweat reabsorption is less affected by nerve activity.

Diarrea crónica como manifestación inicial de un ganglioneuroblastoma / Chronic diarrhea as the initial manifestation of a ganglioneuroblastoma

Resumen: El neuroblastoma es un tumor maligno del sistema nervioso simpático periférico con presentación y curso clínico heterogéneo. Es el tercer tumor pediátrico más frecuente y el 90% de los casos se diagnostica antes de los 5 años. Los síntomas más comunes se deben a la compresión por la masa tumoral o al dolor óseo causado por la metástasis. La diarrea como síntoma principal es rara por lo que es difícil de diagnosticar en la etapa temprana de la enfermedad. Se presenta el caso clínico de una paciente de 2 años en la que luego de 8 meses de estudio por diarrea crónica se diagnóstica ganglioneuroblastoma secretor de VIP. Se debe plantear como diagnóstico diferencial en los pacientes menores de 3 años con diarrea crónica intratable luego de haber descartado otras etiologías.

Summary: Neuroblastoma is a malignant tumor of the peripheral sympathetic nervous system with heterogeneous clinical presentation and course. It is the third most frequent pediatric tumor and in 90% of cases it is diagnosed before 5 years of age. The most typical symptoms result from the tumor compression or bone pain caused by methastasis. Diarrhea as the main symptom is unusual, and thus it is hard to diagnose in early stages of the disease. We report the case of a 2-year-old patient who, after 8 months of study for chronic diarrhea was diagnosed with VIP-secreting ganglioneuroblastoma. It is necessary for this condition to be considered as a differential diagnosis in patients younger than 3 years old with chronic diarrhea with no evolution, after other etiologies are ruled out.

Effects of vasoactive intestinal peptide on airway inflammation and Th17/Treg balance in asthmatic mice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of vasoactive intestinal peptide (VIP) on the airway inflammation and its regulatory effect on Th17/Treg imbalance in asthmatic mice.</p><p><b>METHODS</b>A total of 30 BALB/c mice were equally and randomly divided into three groups: control, asthma, and VIP. An acute asthmatic mouse model was established by sensitization and challenge with ovalbumin (OVA). The control group received normal saline instead of OVA. Before the challenge with OVA, the VIP group was administered VIP (20 μg/mL) by aerosol inhalation for 30 minutes. The bronchoalveolar lavage fluid (BALF) and the lung tissue were collected from mice. The pathological changes in the lung tissue were observed by hematoxylin and eosin staining. The levels of Th17/Treg-related cytokines in BALF were measured by enzyme-linked immunosorbent assay. The expression of retinoid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3) were measured by real-time fluorescence quantitative PCR and immunohistochemistry.</p><p><b>RESULTS</b>The histopathological results showed that the VIP group had milder symptoms of airway inflammation than the asthma group. The level of IL-17 in BALF in the asthma group was significantly higher than that in the control group and the VIP group (P<0.01), but the level of IL-17 in the control group was significantly lower than that in the VIP group (P<0.01). The level of IL-10 in BALF in the asthma group was significantly lower than that in the control group and the VIP group (P<0.01, but the level of IL-10 in the VIP group was significantly higher than that in the control group (P<0.01). The asthma group showed significantly higher expression levels of RORγt mRNA and protein in the lung tissue and significantly lower expression levels of Foxp3 mRNA and protein than the control group (P<0.01). The VIP group had significantly lower expression levels of RORγt mRNA and protein in the lung tissue and significantly higher expression levels of Foxp3 mRNA and protein than the asthma group (P<0.05).</p><p><b>CONCLUSIONS</b>The Th17/Treg imbalance may be closely related to the airway inflammation in asthmatic mice. VIP can improve airway inflammation by regulating the Th17/Treg imbalance in asthmatic mice.</p>

Effect of vasoactive intestinal peptide on defecation and VIP-cAMP-PKA-AQP3 signaling pathway in rats with constipation / 中南大学学报(医学版)

To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.

Experimental studies for botulinum toxin type A to antagonist the VIP/PACAP expression on nasal mucosa in allergic rhinitis rat / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR.@*METHOD@#Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-γ and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made.@*RESULT@#(1)The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group (7.5 ± 0.50) were higher than intervention group (1 ± 0.27) and control group (0.8 ± 0.31). (2) Comparing to intervention group and control group, the serm IFN-γ of the AR group obvious reduced (P < 0.05), the serm IL-4 of the AR group obvious rose (P < 0.01), and the serm Th1/Th2 (IFN-γ/IL-4) of the AR group obvious reduced (P < 0.01). (3) Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously (P < 0.01), and the intervention group of the 3 indexes was obviously than control group. (4) The expression of VIP in the rats' nasal mucosa of the AR group (13.27 ± 2.74) were more intense than intervention group (5.21 ± 2.18) and control group (3.56 ± 5.30) (P < 0.01), and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97 ± 2.14) were more intense than intervention group (6.33 ± 3.04) and control group (4.63 ± 1.25) (P < 0.01). (5) In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P < 0.05).@*CONCLUSION@#The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/ PACAP.

Expression of vasoactive intestinal peptide in peripheral blood of children with hand, foot and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the expression of vasoactive intestinal peptide (VIP) in peripheral blood of children with hand, foot and mouth disease and its significance.</p><p><b>METHODS</b>According to the condition of the disease, 86 children with hand, foot and mouth disease were classified into phase 1 group (19 children) and phase 2 group (67 children). ELISA was used to measure the concentrations of plasma VIP, interferon-γ (IFN-γ), and interleukin-4 (IL-4) in peripheral blood. Flow cytometry was used to measure CD3, CD4, and CD8T lymphocyte subsets. RT-PCR was used for qualitative detection of enterovirus 71 (EV71) RNA in stool.</p><p><b>RESULTS</b>Compared with the phase 1 group, the phase 2 group had a significantly higher positive rate of EV71-RNA (P<0.05) and significantly higher serum levels of IgG, IgA, IgM, and C3 (P<0.05). The phase 2 group had significantly lower proportions of peripheral CD3, CD4, and CD8T lymphocyte subsets than the phase 1 group (P<0.05), as well as significantly lower proportion of peripheral B cells and CD4/CD8ratio than the phase 1 group (P<0.05). The phase 2 group also had a significantly lower concentration of VIP in peripheral blood than the phase 1 group (P<0.05). In the 86 children with hand, foot and mouth disease, the concentration of VIP in peripheral blood was positively correlated with the proportion of CD4T lymphocyte subset and CD4/CD8ratio (r=0.533 and 0.532 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>VIP may be an important marker of the severity of hand, foot and mouth disease.</p>

The effects of sacral nerve root electrostimulation on the colon function and its mechanisms in a rat model of spinal cord injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI).</p><p><b>METHODS</b>One hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8).</p><p><b>RESULTS</b>In SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP.</p>

Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.

Human nasociliary nerve with special reference to its unique parasympathetic cutaneous innervation / 대한해부학회지

The frontal nerve is characterized by its great content of sympathetic nerve fibers in contrast to cutaneous branches of the maxillary and mandibular nerves. However, we needed to add information about composite fibers of cutaneous branches of the nasociliary nerve. Using cadaveric specimens from 20 donated cadavers (mean age, 85), we performed immunohistochemistry of tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal polypeptide (VIP). The nasocilliary nerve contained abundant nNOS-positive fibers in contrast to few TH- and VIP-positive fibers. The short ciliary nerves also contained nNOS-positive fibers, but TH-positive fibers were more numerous than nNOS-positive ones. Parasympathetic innervation to the sweat gland is well known, but the original nerve course seemed not to be demonstrated yet. The present study may be the first report on a skin nerve containing abundant nNOS-positive fibers. The unique parasympathetic contents in the nasocilliary nerve seemed to supply the forehead sweat glands as well as glands in the eyelid and nasal epithelium.

Three Gaseous Neurotransmitters, Nitric oxide, Carbon Monoxide, and Hydrogen Sulfide, Are Involved in the Neurogenic Relaxation Responses of the Porcine Internal Anal Sphincter

BACKGROUND/AIMS: The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. METHODS: Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. RESULTS: Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 muM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 muM). Contractile responses were also reduced (by 45% at 5 Hz, P carbon monoxide > hydrogen sulfide.

Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome

BACKGROUND/AIMS: Previous studies have revealed that mast cells (MCs) may activate the protease-activated receptors and release of neuropeptides involved in the pathogenesis of irritable bowel syndrome (IBS). The levels of protease-activated receptor 2 (PAR-2) and tryptase can contribute to understanding the pathogenesis of IBS. METHODS: Colonoscopic biopsies were performed of 38 subjects (20 with IBS-diarrhea [IBS-D], eight with IBS-constipation [IBS-C], and 10 healthy volunteers). The mRNA and protein levels of tryptase and PAR-2 were assessed by real-time PCR and Western blot. The levels of vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were measured by immunohistochemistry, and MCs were counted by toluidine blue staining. RESULTS: Significant increases in the mRNA expression of tryptase (p<0.05, IBS-D, IBS-C vs control) and PAR-2 (p<0.05, IBS-D, IBS-C vs control) and in the tryptase protein level (p<0.05, IBS-D, IBS-C vs control) were detected in IBS. Elevations of MCs, CGRP, VIP and SP (p<0.05, IBS-D vs control) were observed for IBS-D only. CONCLUSIONS: Tryptase levels may upregulate the function of PAR-2, resulting in the release of neuropeptide and they were correlated with clinical symptoms associated with IBS.

effect of treatment from the lung and treatment from the intestine on vasoactive intestinal peptide contents of ulcerative colitis rats: a comparison study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.</p><p><b>METHODS</b>The UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.</p><p><b>RESULTS</b>Compared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).</p><p><b>CONCLUSION</b>Treatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.</p>

The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats.@*METHOD@#We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry.@*RESULT@#We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P 0.05).@*CONCLUSION@#These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

Composite nerve fibers in the hypogastric and pelvic splanchnic nerves: an immunohistochemical study using elderly cadavers / 대한해부학회지

To determine the proportion of nerve fibers in the hypogastric nerve (HGN) and pelvic splanchnic nerve (PSN), small tissue strips of the HGN and PSN from 12 donated elderly cadavers were examined histologically. Immunohistochemistry for neuronal nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) was performed. More than 70% of fibers per bundle in the HGN were positive for TH at the level of the sacral promontory. In addition, NOS- (negative) and/or VIP+ (positive) fibers were observed in small areas of each nerve bundle, although the proportion of each was usually less than 10%. In the PSN near the third sacral nerve root, the proportion of nerve fibers positive for NOS and/or VIP (or TH) was below 30%. In both the HGN and PSN, the number of VIP+ fibers was usually greater than that of NOS+ fibers, with frequent co-localization of NOS and VIP. More fibers in both nerves were positive for TH than for these other markers. In contrast to pelvic plexus branches, there were no differences in the proportions of NOS+ and VIP+ fibers between nerve bundles in each of the tissue strips. Thus, target-dependent sorting of nerve fibers was not apparent in the HGN at the level of the sacral promontory or in the PSN near the third sacral nerve root. The NOS+ and/or VIP+ fibers in the HGN were most likely ascending postganglionic fibers to the colon, while those in the PSN root may be preganglionic fibers from Onuf's nucleus.

Preliminary study on pharmacodynamic evaluation method of Houpo formula particles / 中国中药杂志

To discuss the feasibility of the pharmacodynamic evaluation method for traditional Chinese medicine (TCM) formula particles, with traditional decoction for reference and the intervention of Magnoliae Officinalis Cortex in rats with ulcerative colitis (UC). First of all, the similarity of traditional Magnoliae Officinalis Cortex decoction and formula particles of different manufacturers was defined by using the IR fingerprint. The UC rat model was established and given Houpo formula particles of different doses and manufacturers, with the decoction for reference, in order to observe disease activity index (DAI), colon mucosa damage index (CMDI), pathologic changes, nitric oxide (NO), endothdin (ET), substance P, vasoactive intestinal peptide (VIP). Their intervention effects on UC rats were compared to study the difference between Sanjiu and Tianjiang Houpo formula particles, in order to demonstrate the feasibility of the pharmacodynamic evaluation method for Houpo formula particles. According to the results, Houpo formula particles showed similar pharmacodynamic actions with the traditional decoction. The pharmacodynamic comparison of Houpo formula particles of different manufacturers showed no statistical significance. The experiment showed that on the basis of the TCM compounds, a prescription dismantlement study was conducted to define target points of various drugs. The traditional decoction was selected for reference in the comparison of corresponding formula particles for their pharmacodynamic equivalence. This method could avoid controversies about single or combined boiling of formula particles, and give objective comments on the pharmacodynamic effect of the formula particles. The method is proved to be feasible.