Differences and significance of motilin,vasoactive intestinal peptide and gastrin in blood and gallbladder tissues of patients with gallstones

BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01). CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

Ulcerative colitis(UC)is a chronic relapsed intestinal disease with an increasing incidence around the world.The pathophysiology of UC remains unclear.However,the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot.Vasoactive intestinal peptide(VIP)is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity.It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system.Regulatory B cells(Bregs)are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles.Bregs can regulate immune tolerance by producing interleukin(IL)-10,IL-35,and transforming growth factor-β,suppressing autoimmune diseases or excessive inflammatory responses.The secretion of IL-10 by Bregs induces the development of T helper(Th)0 and Th2 cells.It also induces Th2 cytokines and inhibits Th1 cytokines,thereby inhibiting Th1 cells and the Th1/Th2 balance.With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients,we believe that Bregs can provide a novel strategy for the clinical treatment of UC.Thus,we aim to review the current literature on this evolving topic.

Vasoactive intestinal peptide,a promising agent for myopia?

AIM： To investigate the role of vasoactive intestinal peptide（VIP） in form-deprivation myopia（FDM）.METHODS： FDM was created in three groups of eight chicks by placing a translucent diffuser on their right eyes.Intravitreal injections of saline and VIP were applied once a day into the occluded eyes of groups 2 and 3,respectively.Retinoscopy and axial length（AL） measurements were performed on the first and 8^th days of diffuser wear.The retina mR NA levels of the VIP receptors and the ZENK protein in right eyes of the three groups and left eyes of the first group on day 8 were determined using real time polymerase chain reaction（PCR）.RESULTS： The median final refraction（D） in right eyes were-13.75（-16.00,-12.00）,-11.50（-12.50,-7.50）,and-1.50（-4.75,-0.75） in groups 1,2,and 3,respectively（P〈0.001）.The median AL（mm） in right eyes were 10.65（10.00,11.10）,9.90（9.70,10.00）,and 9.20（9.15,9.25） in groups 1,2,and 3,respectively（P〈0.001）.The median delta-delta cycle threshold（CT） values for the VIP2 receptors were 1.07（0.82,1.43）,1.22（0.98,1.65）,0.29（0.22,0.45） in right eyes of groups 1,2,and 3,and 1.18（0.90,1.37） in left eyes of group 1,respectively（P=0.001）.The median delta-delta CT values for the ZENK protein were 1.07（0.63,5.03）,3.55（2.20,5.55）,undetectable in right eyes of groups 1,2,and 3 and 1.89（0.21,4.73） in left eyes of group 1,respectively（P=0.001）.CONCLUSION： VIP has potential inhibitory effects in the development of FDM.

Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas

AIM： To study the effect of vasoactive intestinal peptide （VIP） on wound healing in experimental alkali burns of the cornea. METHODS： Twenty-seven albino rabbits, weighing 3.2 -0.75 kg were used. Alkali burns were induced on corneas by applying 10 mm Whatman paper No：50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows： 1） control group given no treatment （n=5）; 2） VIP given subconjunctivally （n=6）; 3） VIP injected into anterior chamber （n=6）; 4） NaCI 0.9% given subconjunctivally （n=5）; 5） NaCI 0.9% given into the anterior chamber （n=5）. All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 a.mo to 6 p.m, RESULTS： VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes （PMNL） infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 （P〈0.05）. CONCLUSION： We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenaees and this might prevent the extracellular amorphous substance loss.

Role of vasoactive intestinal peptide in Aspergillus fumigatus-infected cornea

AIM： To investigate the anti-inflammatory role of vasoactive intestinal peptide（VIP） in Aspergillus fumigatus（A. fumigatus） ketatitis.METHODS： Expression of VIP was tested by polymerase chain reaction（PCR） in C57BL/6 and BALB/c normal and A. fumigatus infected corneas. C57BL/6 mice were pretreated with recombinant（r） VIP, while BALB/c mice were pretreated with VIP antagonist, and then infected with A. fumigatus. Clinical score was recorded. Expression of pro-and anti-inflammatory cytokines, toll-like receptor 4（TLR4）, lectin-like oxidized low-density lipoprotein receptor 1（LOX-1）, and neutrophil infiltration were tested by PCR, enzyme-linked immunosorbent assay（ELISA）, and myeloperoxidase（MPO） assay.RESULTS： VIP mR NA expression in BALB/c cornea was higher than C57BL/6 cornea at 1 and 3 d post infection（p.i.）. rV IP treatment of C57BL/6 mice showed alleviated disease and down-regulated expression of interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α）, while IL-10 expression was up-regulated. Neutrophil infiltration and TLR4, IL-17 expression were decreased after rVIP treatment, while LOX-1 expression was up-regulated in C57BL/6. VIP antagonist pretreatment showed increased disease and higher IL-1β, TNF-α, TLR4, IL-17 and MPO levels, while IL-10 and LOX-1 levels were down-regulated in BALB/c mice.CONCLUSION： rVIP alleviate disease response of C57BL/6 mice. VIP antagonist resulted in worsened disease of BALB/c mice. VIP proposed anti-inflammatory role in A. fumigatus keratitis.

Vasoactive intestinal peptide secreting tumour:An overview

Vasoactive intestinal peptide(VIP)secreting tumour(VIPoma)is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells.These present as sporadic,solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year.Only around 5%of VIPomas are associated with multiple endocrine neoplasia type I syndrome.Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhoea,hypokalemia and metabolic acidosis.These coupled with elevated plasma levels of VIP are diagnostic.The majority of VIPomas are malignant and have already metastasized at the time of diagnosis(60%).Metastases occur most frequently in the liver,or regional lymph nodes,lungs,kidneys and bones.Some reports of skin metastases have been documented.Complete surgical resection continues to be the only potentially curative treatment.However,when the neoplasia cannot be excised completely,surgical debulking may provide palliative benefit.Other palliative options have included recently the peptide receptor radionuclide therapy which has shown to be effective and well-tolerated.This article will review all aspects of pancreatic VIPomas highlighting aspects such as clinical presentation,diagnosis and management.

Plasma Concentration of the Novel Peptide Apelin is Regularly Changed in Patients With Heart Failure

Objectives Apelin, the novel endogenous ligand for the G-protein-coupled receptor APJ, has been observed in many animals and humans studies. It is concluded that it has inotropic effects, hypotension and diuretic properties. The change of apelin in relation to heart failure is still controversial. Our goal was to observe the change of apelin-12 in patients with heart failure （HF）. Methods From 2005 to 2006, 81 consecutive patients （46 male and 35 female, mean age 68.5±12.1 years） with heart failure resulting from variable etiologies and 15 healthy controls were included in this study. Plasma concentration of apelin-12 was measured through ELISA on admission. All patients received conventional therapy and recorded detailed the clinical conditions. Results （1） Plasma concentration of apelin of the controls is lower than the ones of heart failure patients. （2） Plasma concentration of apelin is increased in the early stage and decreased in the advanced period. （3） Apelin is related with variable indexes in the Pearson＇s association analysis. Apelin is also changed with the atrium and ventricular＇s diameter. Conclusions Plasma concentration of apelin is increased in early stage and decreased in advanced period. The apelin-APJ system might be important in the pathophysiological process of heart failure. And it might be valuable in diagnosis and therapeutic implications in heart failure.

Cardiac Autonomic Control in Relation to Other Prognostic Markers in Idiopathic Dilated Cardiomyopathy

Objectives: We set out to study cardiac autonomic tone in patients with idiopathic dilated cardio-myopathy (IDC), and whether it correlates with other established markers of disease progression and patient ultimate outcome. Design: Fifty-one IDC patients in sinus rhythm underwent extensive non-invasive and invasive evaluation during a three-day hospitalization period. The control group consisted of thirty-eight apparently healthy subjects who underwent 24-hour ambulatory ECG recording. Results: Heart rate variability (HRV) and heart rate turbulence (HRT) correlated with many previously established prognostic markers of IDC and congestive heart failure, especially measures of cardiorespiratory performance capacity and circulating neurohumoral factors (p < 0.05 for all). Furthermore, attenuated HRV correlated with worse prognosis during a median follow-up of 6.8 years (range 5.1 - 8.1). Additionally, 24-hour time domain, low and high frequency components of frequency domain and non-linear HRV, excluding scaling exponents (α), were lower in IDC patients as compared with controls (p < 0.05 for all);however, HRT was not significantly different. Conclusions: The magnitude of impairment in cardiac autonomic control correlates well with other prognostic markers of IDC, and is associated with unfavorable outcome.

Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating,qi-replenishing and blood-containing formula

Objective:This study investigated the regulatory effect of non-classical immune parameters on immune thrombocytopenic purpura(ITP)mice by a spleen-invigorating,qi-replenishing and blood-containing formula(SQBF).Method:A total of 80 BALB/c mice were randomly divided into four equal groups(20 mice each):control group,model group,prednisone group and spleen-invigorating,qi-replenishing and blood-containing(SQBF)group.Mice in the model group,prednisone group,and SQBF group were administered anti-platelet serum to induce ITP.The dynamic variations of platelet counts in ITP mice were measured with an automatic blood analyzer before modeling and 48 h,and 8,12 and 15 days following APS injection.Levels of b-endorphin(b-EP),vasoactive intestinal peptide(VIP)and salivary IgA(SIgA)were detected by enzyme-linked immunosorbent assay(ELISA)on 15th day of experiment.Results:SQBF enhanced peripheral blood platelet counts in ITP mice similar to that of prednisone,and both groups showed a statistically significant response compared with the model group(P<.01).The SQBF significantly decreased b-EP levels compared with the model and prednisone intervention groups(P<.05),significantly increased the levels of VIP and SIgA in ITP mice compared with the model group(P<.05)and had significant protective effects on the thymus of ITP mice compared with the model group(P<.01).Conclusions:The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice.Furthermore,it decreased b-EP levels and increased VIP and SIgA,and protected the thymus.This shows that,on base of the brain-gut axis functions,some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses,and also have relationship with the onset of ITP and bleeding and/or hemostasis.It needs further study to determine whether a change in these active factors is related to immediate hemostasis.

The Expression of VIP and SP in the Cochlea of Spontaneously Hypertensive Rats and Its Implication

To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR), and to assess the function of VIP and SP in the cochlea following the damage of hypertension, hearing thresholds of ABR were observed and the fixative (4% paraformaldehyde) was pumped through the circulatory system. Adult Wistar rats (3 months, n=20) served as the control group and SHRs (3 months, n=20) as the hypertension group. Bullas were taken out and cochleas were irrigated in vitro with the same fixative. The number of base turn's spiral ganglions in the sections was counted. The expression of VIP and SP were detected by SABC method and the images of the sections were analyzed. The number of base turn's spiral ganglsons in the hypertension group was significantly less than in the normal group (P<0.01). VIP and SP were expressed in the spiral ganglion cytoplasma and stria vascularis of the two groups. There were no significant difference in the expression of VIP and SP in spiral ganglion cytoplasma (P>0.05) between the two groups. However, in stria vascularis the expression of VIP in the hypertension group was higher than in the normal group (P<0.05), and no significant difference in SP was found between the two groups. It was suggested that VIP not only contributed to the regulation of the cochlea microcirculation, but also made the neurotransmitter in the pathway of the auditory system. However, SP made only the neurotransmitter in the pathway of the auditory system.

Ameliorating Effect and Potential Mechanism of Camellia Oil on Constipated Mice

Constipation is a global epidemic. To evaluate the ameliorating effect of camellia oil on constipation,two slowtransit costive mice models were established by water deprivation or sucralfate gavage. Administration of camellia oil（ 4. 0 and 8. 0 mL/kg/day） significantly shortened the defecation time,increased defecation mass and fecal water content,with efficacies comparable to that of hemp seed oil. Intestinal propulsion test showed that camellia oil significantly enhanced the propelling rates of the charcoal powder in the intestine. Meanwhile,camellia oil also significantly decreased the serum levels of nitric oxide（ NO）,nitric oxide synthase（ NOS） and vasoactive intestinal peptide（ VIP） and increased serum substance P in costive animals. These results suggested that camellia oil can largely relieve slowtransit constipation and enhance the gastrointestinal motility through modulation of serum gastrointestinal motility key factors such as NO,NOS and VIP and substance P.

Protective Effect of Zengye Decoction(增液汤)on Submandibular Glands in Nonobese Diabetic Mice

Objective: To investigate the protective effect of Zengye Decoction(增液汤, 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 realtime 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.

Correlation between slow transit constipation and spleen Qi deficiency, and gut microbiota: a pilot study

OBJECTIVE:To investigate the effect of slow transit constipation(STC)and spleen Qi deficiency on gut microbiota,and the mechanism underlying the action that the positive drug Maren Runchang(MR)alleviates STC.METHODS:STC was induced,using the cathartic method of Senna and the hunger-fullness disorder method,in ICR mice;one group of model mice was treated with MR(6.24 g/kg).The changes in the general condition,fecal parameters,D-xylose content in the serum,intestinal propulsion rate,and histopathology of the colon were assessed after STC induction in the control,model,and MR groups.Fecal microbiota transplantation(FMT)was performed from STC mice into pseudo germ-free mice.Changes in the contents of substance P(SP),vasoactive intestinal peptide(VIP),and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.RESULTS:Compared with the control group,the model mice showed the following results:the time of the first black stool was significantly longer(P<0.01),the number and weight of black stools were significantly reduced within 6 h(P<0.05),the D-xylose content in the serum was significantly reduced(P<0.05),the intestinal propulsion rate decreased(P<0.01),the content of VIP in colon tissue significantly increased(P<0.05),and SP content in the colon tissue significantly decreased(P<0.01);moreover,the colon showed significant inflamemation and injury.Furthermore,the abundance of Firmicutes was increased,the abundance of Bacteroides decreased,and the abundance of Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus decreased,while the abundance of the conditional pathogenic bacteria Escherichia and Klebsiella increased.However,after treatment with MR,the time of the first black stool decreased(P<0.01),the number of black stools within 6 h increased,and the intestinal propulsion rate increased(P<0.05).Moreover,the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and colon inflammation significantly improved.Additionally,the abundance of Firmicutes decreased,and the abundance of Bacteroides increased.The abundance of unclassified_o_Bacteroidales and Bilophila increased,and the abundance of Klebsiella decreased.In the model+FMT group,compared with control+FMT group,the content of VIP in colon tissue decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and the abundance of probiotics,such as Lactobacillus and Akkermansia,decreased.In the MR+FMT group,compared with the model+FMT group,the content of VIP in colon tissue increased,the content of SP in colon tissue significantly decreased(P<0.01),and the abundance of probiotics increased.CONCLUSIONS:STC mice with spleen Qi deficiency show a decreased abundance of beneficial bacteria,such as Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus,and an increased abundance of the conditional pathogenic bacteria Escherichia coli and Klebsiella.Furthermore,the mechanism of action of MR in treating STC may involve the regulation of intestinal movement,reduction of intestinal inflammation,elevation of intestinal absorption,and regulation of gut microbiota.

Changes in Small Intestinal Motility and Related Hormones by Acupuncture Stimulation at Zusanli(ST 36) in Mice

Objective： To clarify the effects of acupuncture stimulation at Zusanli（ST 36） on the hormonal changes. Methods： Eight-week-old male C57BL/6 mice received acupuncture stimulation at acupoint ST 36 or Quchi（LI 11） once a day for 3 or 5 days in the acupuncture-stimulated groups, but not received in the normal group（n=6 in each group）. On day 3 or 5, animals were given 0.1 m L of charcoal orally with a bulbed steel needle, 30 min after the last acupuncture stimulation. Ten minutes later, mice were anesthetized, and the intestinal transit and the concentrations of vasoactive intestinal peptide（VIP）, motilin, ghrelin and gastrin in the serum were measured. Results： Compared to no acupuncture stimulation, acupuncture stimulation at ST 36 for 5 days increased the intestinal transit and down-regulated the concentration of VIP and up-regulated the concentrations of motilin, ghrelin and gastrin（P〈0.05 or 0.01）, whereas acupuncture stimulation at LI 11 did not change them significantly（P〉0.05）. Conclusion： Acupuncture stimulation at ST 36 for 5 days enhances the small intestinal motility and regulates the secretion of hormones related to small intestinal motility.

A Whole-brain Map of Long-range Inputs to GABAergic Interneurons in the Mouse Caudal Forelimb Area

The caudal forelimb area(CFA)of the mouse cortex is essential in many forelimb movements,and diverse types of GABAergic interneuron in the CFA are distinct in the mediation of cortical inhibition in motor information processing.However,their long-range inputs remain unclear.In the present study,we combined the monosynaptic rabies virus system with Cre driver mouse lines to generate a whole-brain map of the inputs to three major inhibitory interneuron types in the CFA.We discovered that each type was innervated by the same upstream areas,but there were quantitative differences in the inputs from the cortex,thalamus,and pallidum.Comparing the locations of the interneurons in two subregions of the CFA,we discovered that their long-range inputs were remarkably different in distribution and proportion.This whole-brain mapping indicates the existence of parallel pathway organization in the forelimb subnetwork and provides insight into the inhibitory processes in forelimb movement to reveal the structural architecture underlying the functions of the CFA.

Effect of salvia miltiorrhiza pretreatment on the CCK and VIP expression in hepatic ischemia-reperfusion-induced digestive tract congestion

The inhibitory effect of different reperfusion periods 45 min following hepatic ischemia on the expression of cholecystokinin(CCK)and vasoactive intestinal peptide(VIP)in the jejunum and the effect of salvia miltiorrhiza pretreatment were investigated,and the possible mechanism and implications were explored.Eighty rats were randomly divided into four groups:normal control group(CO group),sham-operated group(SO group),ischemia/reperfusion(I/R)injury group(IR group)and salvia miltiorrhiza pretreatment group(SM group).The rat model of I/R was established by using a non-invasive artery clamp to clip(45 min)or relax the hepatic pedicle.In the SM group,saline(40 mL/kg)and salvia miltiorrhiza injection(6 g/kg)were injected via the tail vein 30 min before clipping the hepatic pedicle.In the SO group only the porta hepatis was dissected after laparotomy without clamping the hepatic pedicle.At 0,3,12,24 and 72 h post-reperfusion,respectively,upper jejunum samples were taken for immunohistochemistry of CCK and VIP.It was found that 0 h after I/R,the expression of CCK and VIP in the upper jejunum was upregulated.With prolongation of the reperfusion period,the expression of CCK and VIP was also increased,reached the peak at the 24th h,and gradually returned to the normal level at the 72nd h after reperfusion.The levels of both CCK and VIP in the SM group were lower than those in the IR group.It is suggested that the digestive tract congestion injury caused by liver ischemia can upregulate the expression of CCK and VIP in the jejunum following reperfusion.Salviae pretreatment can partly reduce the increased expression of CCK and VIP in the jejunum in the same period,which might contribute to the early recovery of gastrointestinal motility.