Vasoactive Intestinal Peptide Levels Research Articles

Evaluation of the Circadian Rhythm Neuropeptides and Hippocampus in Rat Model of Posttraumatic Stress

ABSTRACT We investigated hippocampus weight and the levels of circadian rhythm-related neuropeptides; Somatostatin (SST), Vasoactive Intestinal Peptide (VIP), Neuropeptide Y (NPY), Melatonin (MLT), and Corticotrophin Releasing Hormone (CRH) in plasma (p) and hippocampus tissue (h) of rats with posttraumatic stress (PTS) symptoms. Thirty four healthy Spraque-Dawley rats were randomly divided into control and PTS groups. Single prolonged stress (SPS) model was used to mimic PTS. Elevated Plus Maze Test (EPMT) was used to assess anxiogenic behavior. Rats were sacrificed under anesthesia and hippocampus weight, SST, NPY, CRH, MLT, and VIP levels were measured by the Enzyme-Linked-Immuno-Sorbent-Assay method. Hippocampus weights in the PTS group were significantly lower compared to controls. NPYh and MLTh levels were significantly higher in the PTS group. NPYh and MLTh and MLTp were significantly higher in the PTS. CRH, VIP, and SST levels in hippocampus tissue and CRH, NPY, VIP, and SST in plasma did not differ between groups. A positive correlation was found between MLTh and VIPh tissue levels. There was a positive correlation between NPYh and VIPh levels, and a high degree of positive correlation between NPYp and VIPp levels. As far as we know, this is the first study in which 5 neuropeptides’ hippocampus tissue and plasma levels were evaluated together in a PTSD model. Hippocampus weights may tend to decrease in PTS. Especially, NPY and MLT from circadian rhythm neuropeptides play an important role in PTS etiology. After the 7th day of trauma exposure, the hippocampal NPY and MLT levels may increase as a stress-adaptive mechanism in PTS.

S3640 Myoclonic Jerks and Chronic Diarrhea; The Challenges of Zollinger-Ellison Syndrome

Introduction: Zollinger-Ellison Syndrome (ZES) is a rare disorder caused by hypersecretion of gastrin, causing peptic ulcer disease (PUD) and diarrhea. In most cases, inappropriate gastrin secretion is from duodenal or pancreatic neuroendocrine tumors (gastrinoma). Diagnosis of gastrinoma can be delayed as symptoms are nonspecific and can be misdiagnosed as other GI disorders. Case Description/Methods: A 79yo female with DM, HTN, and peptic ulcer disease presented with myoclonic jerks and watery diarrhea. She was found to have severe hypomagnesemia and acute kidney injury (AKI). Notably she had diarrhea for months with several admissions with similar symptoms. Prior workup including celiac serology, vasoactive intestinal peptide level, fecal calprotectin, and colonoscopy were inconclusive. Lomotil was started for possible irritable bowel syndrome (IBS) with partial response. On this admission, stool osmolar gap was < 50, chromogranin A 8224 ng/mL and gastrin 596 pg/mL. MRI of the abdomen showed a 2.5cm mass-like thickening in the distal gastric antrum. Endoscopy showed gastritis and duodenal ulcers. EUS with FNA of the mass was inconclusive. Octreoscan revealed a somatostatin receptor-bearing neuroendocrine tumor (NET) in the distal stomach. She underwent distal gastrectomy and peri-pancreatic LN resection after hospitalization. Histopathology confirmed a well-differentiated NET with metastasis. Her diarrhea resolved and chromogranin A and gastrin normalized, 90 ng/mL and 43 pg/mL respectively. (Figure) Discussion: Chronic diarrhea is a main symptom of gastrinomas. Diagnosis can be challenging due to the rarity of ZES and as many disorders cause diarrhea. Many patients are diagnosed with more common conditions such as IBS and GERD. Initial evaluation in suspected cases includes Gastrin levels which can be falsely elevated in patients on chronic PPI. Most gastrin-producing tumors arise in the duodenum (75%) and pancreas (20%). Less than 5% of patients have a tumor in the stomach, peri-pancreatic lymph nodes, liver, bile ducts, or ovary. EGD can show prominent gastric folds and pathology can be nonspecific. In patients with suspected ZES, chest and abdominal imaging can identify intra or extra-abdominal lesions. Octreoscan can localize the tumor’s primary location and any metastasis. Consideration of ZES in patients with chronic diarrhea with timely evaluation and treatment can prevent the complications such as electrolyte abnormality, PUD, and decreases risk of metastasis.Figure 1.: a,b. Duodenal Ulcers. Image c. 2.5 cm mass-like thickening with restricted diffusion in the distal gastric antrum suspicious for neoplasm with an adjacent 1.5 cm lymphadenopathy.

Effects of Simo decoction on gastric motility of diabetic rats.

To investigate the effects of simo decoction (SMD) on the gastric motility of diabetic rats. Diabetic rats were gavaged with various doses of SMD (0.15, 1.5, and 3.0ml/kg/d) or saline, and their blood glucose levels and body weight were monitored. Gastric emptying and antral motility were assessed by phenol red retention and contractions of antral strips, respectively. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and neurogenic nitric oxide synthase (nNOS) in the gastric antrum were determined by real-time polymerase chain reaction and Western blot. Gastric emptying was delayed in diabetic rats (p< 0.01 vs. non-diabetic controls) but accelerated after SMD administration (p< 0.01). The contractions of antral strips were reduced in diabetic rats (p< 0.01 vs. non-diabetic controls) but improved after SMD intervention (p< 0.05). The mRNA expressions of SP, VIP, and nNOS in diabetic rats were downregulated compared with non-diabetic controls (all p< 0.01). Simo decoction treatment did not affect the expression of these factors in diabetic rats. The protein levels of SP, VIP, and nNOS in diabetic rats were decreased (p< 0.01), increased (p< 0.01), and comparable (p> 0.05), respectively, in comparison with non-diabetic controls. Simo decoction administration increased SP protein expression (p< 0.01) and decreased the levels of VIP (p< 0.01) and nNOS (p< 0.01) in diabetic rats. Simo decoction improved gastric dysmotility of diabetic rats possibly by upregulating SP and downregulating VIP and nNOS.

Effectiveness of Laparoscopic Cholecystectomy in Patients with Gallbladder Stones with Chronic Cholecystitis.

Objective To assess the effectiveness of laparoscopic cholecystectomy in patients with gallbladder stones and chronic cholecystitis. Methods From July 2018 to January 2020, 90 patients with gallbladder stones and chronic cholecystitis assessed for eligibility were recruited and concurrently assigned (1 : 1) to receive either small-incision cholecystectomy (observation group) or laparoscopic cholecystectomy (experimental group). Outcome measures included operation time, intraoperative bleeding volume, postoperative hospital stay, c-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-α (TNF-α), gastrin (GAS), vasoactive intestinal peptide (VIP), motilin (MOT), and adverse events. Results Patients given laparoscopic cholecystectomy showed lower levels of operation-related indices versus those receiving small-incision cholecystectomy (P < 0.05). Laparoscopic cholecystectomy resulted in lower postoperative levels of CRP, IL-6, and TNF-α in the patients versus small-incision cholecystectomy (P < 0.05). Patients receiving laparoscopic cholecystectomy showed better GAS, VIP, and MOT levels than those receiving small-incision cholecystectomy (P < 0.05). The eligible patients after laparoscopic cholecystectomy had a significantly lower incidence of adverse events versus those after small-incision cholecystectomy (P < 0.05). Conclusion Laparoscopic cholecystectomy effectively shortens the operative time and length of hospital stay in patients with gallbladder stones and chronic cholecystitis, reduces intraoperative bleeding, attenuates the inflammatory response, and enhances the gastrointestinal function, with less surgical trauma and high safety. Clinical trials are, however, required prior to promotion.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves’ disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Comparing VIP and PD‐L1 expression as cancer biomarkers

AbstractImmune checkpoint molecules are critical targets of cancer therapies due to their ability to modulate immune responses to cancer. Vasoactive intestinal peptide (VIP) has been proposed as an immune checkpoint molecule, but its predictive and prognostic values have not been established. We evaluated expression levels of VIP and programmed death‐ligand 1 (PD‐L1) across different cancer types and identified specific cancer histologies in which the expression of these markers is elevated. We conducted systematic analyses of the prognostic and predictive values of VIP and PD‐L1 in various cancers using publicly available patient databases and analysis tools including the Gene Expression Profiling Interactive Analysis, PrognoScan, Protein Atlas, cBioportal, and Timer2.0. We also assessed the relationship of PD‐L1 and VIP expression levels with survival and the frequencies of tumor‐infiltrating immune cells in various cancers. We observed a negative correlation between PD‐L1 and VIP expression across cancer types, suggesting the functional redundancy of VIP and PD‐L1 immunosuppressive pathways as mechanisms of immune escape. High expression levels of VIP and the association of VIP expression with immune cell infiltrates in the pancreatic adenocarcinoma tumor microenvironment suggest that VIP may be a predictive biomarker for treating pancreatic adenocarcinoma patients with drugs that inhibit the VIP signaling pathway.

Mechanism of Huanglian Houpo Decoction in treatment of ulcerative colitis in mice based on brain-gut axis

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1β, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.

P086 Serum levels of alpha calcitonin gene-related peptide and vasoactive intestinal peptide as predictors of exacerbation in cystic fibrosis

P086 Serum levels of alpha calcitonin gene-related peptide and vasoactive intestinal peptide as predictors of exacerbation in cystic fibrosis

Aqueous Extract of Phyllanthus emblica L. Alleviates Functional Dyspepsia through Regulating Gastrointestinal Hormones and Gut Microbiome In Vivo.

Phyllanthus emblica L. fruits were extracted by a hot water assistant with ultrasonication to obtain aqueous Phyllanthus emblica L. extract (APE). The ameliorating functional dyspepsia (FD) effect of a low dose (150 mg/kg) and a high dose (300 mg/kg) of APE was exhibited by determining the gastrointestinal motility, gastrointestinal hormones, and gut microbiome shifts in reserpine induced FD male balb/c mice. APE increased the gastrointestinal motility including the gastric emptying (GE) rate and small intestinal transit (SIT) rate. The level of serum gastrointestinal hormones such as motilin (MTL) and gastrin (GAS) increased, and the vasoactive intestinal peptide (VIP) level decreased after the administration of APE. Furthermore, the gut microbiome analysis demonstrated that APE could regulate the microbiome structure and restore homeostasis by elevating useful bacterial abundance, while simultaneously decreasing harmful bacterial abundance. This study demonstrated the ameliorating FD effect of APE and its potential efficacy in curing functional gastrointestinal disorders and maintaining a healthy digestive tract.

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.

The Anti-Constipation Effects of Raffino-Oligosaccharide on Gut Function in Mice Using Neurotransmitter Analyses, 16S rRNA Sequencing and Targeted Screening.

Raffino-oligosaccharide (ROS), the smallest oligosaccharide of the raffinose family, is a novel food ingredient. However, the anti-constipation effects of ROS remain obscure. This study investigates the anti-constipation effects of ROS based on the loperamide-induced mice model and reveals the underlying mechanism using constipation parameters, neurotransmitter level, 16S rRNA sequencing, and the targeted screening strategy. The prevention effects were firstly investigated by the gastro-intestinal transit rate experiment (50 mice) and defecation status experiment (50 mice), which were divided into five groups (n = 10/group): blank, model, and low-, medium- and high-dose ROS. Furthermore, the slow-transit constipation experiment (blank, model, and high-dose ROS, n = 10/group) was conducted to illustrate the underlying mechanism. The results showed that ROS aided in preventing the occurrence of constipation by improving the gastro-intestinal transit rate and the defecation frequency in mice, and ROS significantly reduced the serum levels of vasoactive intestinal peptide (VIP). In addition, ROS regulated the diversity and structure of intestinal flora. Among them, one specific family and six specific genera were significantly regulated in constipated mice. The targeted screening revealed that 29 targets related to the anti-constipation effects of ROS, indicating ROS may play a role by regulating multiple targets. Furthermore, the network pharmacology analysis showed that Akt1, Stat3, Mapk8, Hsp90aa1, Cat, Alb, Icam1, Sod2, and Gsk3b can be regarded as the core anti-constipation targets. In conclusion, ROS could effectively relieve constipation, possibly by inhibiting the level of neurotransmitters and regulating the gut flora in mice. This study also provides a novel network pharmacology-based targeted screening strategy to reveal the anti-constipation effects of ROS.

VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells.

Infection by SARS‐CoV‐2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID‐19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP), highly similar neuropeptides, decreased the SARS‐CoV‐2 RNA content in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS‐CoV‐2‐induced activation of NF‐kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF‐kB. Specific inhibition of NF‐kB and SREBP1/2 reproduced the anti‐inflammatory, antiviral, and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID‐19.

Ultrasound-guided stellate ganglion block accelerates postoperative gastrointestinal function recovery following laparoscopic radical gastrectomy for gastric cancer

To explore the effects of ultrasound-guided stellate ganglion block (SGB) on perioperative stress response, gastrointestinal hormones and postoperative gastrointestinal function recovery in patients undergoing laparoscopic radical gastrectomy for gastric cancer. This study was conducted among 60 American Society of Anesthesiologists (ASA) class II-III patients with gastric cancer (regardless of gender, aged 35-75 years with BMI of 18.5-26 kg/m2) undergoing elective laparoscopic radical gastrectomy. The patients were randomized into experimental group (S group, n=30) and control group (NS group, n=30). In S group, SGB at the C6 level of the right cervical spine was performed under ultrasound guidance 15 min before induction of anesthesia by injection of 7 mL 0.5% ropivacaine; the patients in NS group received injections of normal saline in the same manner. Peripheral venous blood samples were collected before SGB (T1), after surgery (T2), and on the 2nd and 6th days after surgery (T3 and T4) for determination of the levels of motitin (MOT), vasoactive intestinal peptide (VIP), cortisol (COR), and blood glucose (GLU). Intraoperative usage of sufentanil, recovery rate of intestinal sounds at 36, 48, 60, 72, 84 and 96 h after operation and the time of first passage of flatus were recorded and compared between the two groups. There was no significant difference in the total amount of sufentanil consumption between the two groups. Compared with those in NS group, the patients in S group had significant lower COR and VIP levels (P < 0.05) and higher MOT level (P < 0.05) at T2, T3 and T4. Glu level at T2 and T3 was also significantly lower in S group (P < 0.05). The recovery rates of intestinal sounds at 36, 48, 60, 72 and 84 h after surgery were significantly higher (P < 0.05) and the time of the first passage of flatus was earlier in S group than in NS group (P < 0.05). In patients with gastric cancer undergoing laparoscopic radical gastrectomy, ultrasound-guided SGB can reduce postoperative stress level, promote the recovery of gastrointestinal hormone secretion, and accelerate postoperative recovery of gastrointestinal functions.

Transdermal Administration of Volatile Oil from Citrus aurantium-Rhizoma Atractylodis Macrocephalae Alleviates Constipation in Rats by Altering Host Metabolome and Intestinal Microbiota Composition.

Background The Citrus aurantium- (ZhiShi, ZS-) Rhizoma Atractylodis Macrocephalae (BaiZhu, BZ) pairs are often found in herbal formulas for constipation. The volatile oils of ZS and BZ (ZBVO) have good pharmacological activity against constipation, but the mechanism for treatment of slow transit constipation (STC) remains unclear. Method A rat model using diphenoxylate tablets was constructed to investigate if transdermal administration of ZBVO would mediate intestinal microorganisms and fecal metabolites and improve STC symptoms. The regulatory effects of ZBVO at 0.15, 0.30, and 0.60 mL kg−1 d−1 on STC rats were assessed by measuring fecal water content, intestinal propulsion rate, histopathology, expression of gastrointestinal hormones, brain and intestinal peptides, and inflammatory factors. The changes in intestinal flora of STC rats were analyzed by 16S rRNA gene sequencing. Moreover, the untargeted fecal metabolomics analysis was performed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS) technology. Results The results showed that ZBVO had a modulating effect on STC by increasing the fecal water content and intestinal propulsion rate. Transdermal administration of ZBVO decreased serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) and increased the levels of gastrin (GAS) and substance P (SP). In addition, ZBVO increased 5-hydroxytryptamine (5-HT) levels and decreased vasoactive intestinal peptide (VIP) levels in colon and hippocampus tissues. The results of intestinal microbiota showed that ZBVO improved the diversity and abundance of intestinal microbiota and changed the community composition by decreasing Romboutsia and increasing Proteobacteria, Allobaculum, and Ruminococcaceae. And the feces metabolomics found that nicotinate and nicotinamide metabolism, purine metabolism, citrate cycle (TCA cycle), pyruvate metabolism, arachidonic acid metabolism, pyrimidine metabolism, and primary bile acid biosynthesis were modulated. Conclusion These findings suggest that ZBVO can alleviate STC symptoms by promoting intestinal peristalsis, increasing fecal water content, regulating gastrointestinal hormone level, reducing the inflammatory response, and regulating brain and intestinal peptides after transdermal administration. And structural changes in the intestinal microbiota are closely related to host metabolism and intestinal microbiota destroyed in STC modeling could be significantly improved by the ZBVO, which provides a reference for the development of aromatic drug macrohealth products.

Changes in esophagus interstitial cells of Cajal in response to acute stress

Background Thoracic trauma is common, and traffic accident-related traumatic injury can cause acute stress leading to esophageal motility disorders. Interstitial cells of Cajal (ICCs) are regarded as gastrointestinal pacemaker cells. Aim This study explored the mechanism underlying changes in lower esophagus ICCs under acute stress conditions. Methods Fifty adult rabbits, randomly divided into one healthy control and four study groups, were subjected to right chest puncture using a Hopkinson bar. Thereafter, one group was immediately subjected to lower esophagectomy, whereas the other three groups were maintained for 24, 48 and 72 h after puncture and subjected to lower esophagectomy. Immunohistochemistry was used to detect ICC distribution, morphology and density, and TUNEL assays were used to determine ICC apoptosis. Enzyme-linked immunosorbent assays (ELISAs) were used to measure cortisol, epinephrine, dopamine, IL-9, cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). Western blotting and RT-PCR were performed to detect changes in SCF/c-kit and nNOS pathways. Results After puncture, lung tissue was hemorrhaged, alveoli in puncture areas were destroyed, esophageal pH was decreased, and serum cortisol, epinephrine and dopamine levels increased. ICC numbers increased and apoptotic ICCs decreased in all stress groups after puncture (all p < .01). IL-9, CCK and VIP levels in lower esophagus tissue were increased after puncture (all p < .01). Moreover, SCF/c-kit and nNOS pathways were upregulated in response to stress (all p < .01). Conclusions Acute stress promotes increases in lower esophageal ICCs that might affect esophagus ICC functions and esophageal motility.

Clinical observation on deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle for trigeminal neuralgia of wind and heat

To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism. A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and β-endorphin (β-EP) were detected, and the adverse reaction was observed in the both groups. After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (P<0.05), and the variations of above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the serum levels of β-EP were increased compared before treatment in the both groups (P<0.05), and the variation of that in the observation group was larger than the control group (P<0.05). No severe adverse reaction was observed in the both groups. Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and β-EP.

Therapeutic Effect of Camel Milk in Children with Autism: Its Impact on Serum Levels of Vasoactive Intestinal Peptide

Background: Camel milk (CAM) regulates the inflammatory process, apoptotic pathways and oxidative stress. Thus, it is a therapeutic possibility for many autoimmune disorders, including autism. Vasoactive intestinal peptide (VIP) is an anti-inflammatory peptide that facilitates the immune regulatory functions by recruiting regulatory T cells to induce immune tolerance and prevent the occurrence of autoimmunity. This study aimed to investigate the effect of CAM consumption on both serum VIP levels and the severity of autism assessed by measuring the Childhood Autism Rating Scale (CARS). Mehods: Sixty-five autistic children, aged between 3-12 years, were studied. Forty-seven patients received 500 mL of CAM (either raw "24 patients" or boiled "23 patients") in their regular daily diet for two weeks. Eighteen patients received 500 mL of cow milk for two weeks. For all patients, CARS and serum VIP levels were assessed before and after milk consumption. Results: Although there was a decrease in CARS scores in patients who received raw CAM, this decrease was non-significant (P=0.070). Serum VIP levels were increased in patients who consumed CAM, either raw (P=0.076) or boiled (P=0.065), but this increase was non-significant. Conclusions: CAM consumption for 2 weeks neither significantly decreased the severity of autism nor increased serum anti-inflammatory VIP levels. The lack of a significant response to CAM in this study may be attributable to the short duration of CAM consumption. Further studies are required to investigate the effect of CAM consumption for a longer duration on serum VIP levels and the severity of autism.

Markers of the sympathetic, parasympathetic and sensory nervous system are altered in the human diabetic choroid

BackgroundWe sought to evaluate alterations in markers of the autonomic nervous system in human diabetic choroid. MethodsEighteen eyeballs from subjects with diabetes and 22 eyeballs from subjects without diabetes were evaluated in this study. Synaptophysin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DβH), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vesicular monoamine transporter II (VMAT-2), vesicular acetylcholine transporter (VAChT), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) levels were detected by western blot analysis and immunofluorescence was performed in some cases. Furthermore, differences in adrenergic (α1- and β2-subtypes) and cholinergic (M1 and M3) receptor levels between diabetic subjects and controls were noted. ResultsDecreased synaptophysin levels were found in diabetic choroids by western blot analysis and a reduction of synaptophysin-immunoreactive nerves was also found by immunofluorescence. Furthermore, a decrease of the levels of the key enzyme (TH) and transporter (VMAT2) of norepinephrine was evident both by western blot analysis and immunofluorescence. Additionally, increased NPY, VAChT, nNOS, and CGRP levels were observed in diabetic choroids. The levels of adrenergic (β2 subtype) and acetylcholine (M1 subtype) receptors decreased in diabetic choroids, as shown by western blotting and although the differences in α1 and M3 were not significant, there was a downward trend. ConclusionsIn the diabetic choroid, the levels of neurotransmitters, enzymes, and receptors associated with choroidal blood flow regulation are altered. These changes may affect the regulation of choroidal blood flow and may be associated with impaired retinal function and retinal pathology.

Гендерні аспекти впливу вазоінтестинального пептиду та інтерлейкіну-5 на показники екстракраніальної гемодинаміки в дітей із бронхіальною астмою

Актуальність. Огляд вітчизняної та зарубіжної науково-дослідної літератури свідчить, що на сьогодні системні наукові дослідження щодо взаємозв’язку між рівнем нейропептиду VIP (вазоактивний інтестинальний пептид — vasoactive intestinal peptide) та інтерлейкіну-5 у сироватці крові та станом мозкової гемодинаміки у хворих на бронхіальну астму дітей відсутні. Метою дослідження було встановити можливі впливи нейропептиду VIP та інтерлейкіну-5 на показники екстракраніальної гемодинаміки у хворих на бронхіальну астму дітей, проаналізувати гендерні особливості цих показників. Матеріали та методи. Проведено імунологічне дослідження сироватки крові для визначення рівня нейропептиду VIP та інтерлейкіну-5 у 54 хворих на бронхіальну астму дітей, серед яких були 21 дівчинка та 33 хлопчики віком 10–17 років. Контрольну групу становили 20 здорових дітей, які були ідентичні хворим за гендерним та віковим складом. Діти були обстежені двічі — при неконтрольованому та контрольованому перебігу хвороби. Також усім дітям проведено ультразвукове допплерографічне дослідження магістральних судин голови та шиї. Результати. Аналіз рівнів нейропептиду VIP та інтерлейкіну-5 установив гендерну залежність їх коливань: рівень нейропептиду VIP був статистично нижчим, а інтерлейкіну-5 — вищим у хворих хлопчиків із неконтрольованим перебігом бронхіальної астми порівняно із здоровими хлопчиками. У хворих із контрольованим перебігом бронхіальної астми негативний вплив на показники екстракраніальної гемодинаміки є мінімальним як у дівчаток, так й у хлопчиків. Висновки. Для здійснення дієвого контролю над перебігом захворювання потрібно враховувати зміни показників екстракраніальної гемодинаміки у хворих на бронхіальну астму дітей залежно від їх статі, що дозволить уникнути цереброваскулярних ускладнень у даного контингенту хворих.

Correlation of Decreased Serum Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Levels With Non-motor Symptoms in Patients With Parkinson's Disease.

Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines, and the behavior of immune cells. However, the relationship between PACAP and VIP levels and Parkinson’s disease (PD) are not clear. The aim of the current study was to evaluate serum PACAP and VIP levels in PD patients and to analysis the correlation between neuropeptide levels and non-motor symptoms.Methods: In this cross-sectional study, we enrolled 72 patients with idiopathic PD and 71 healthy volunteers. Serum PACAP and VIP levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS) for PD, including total and single-item scores.Results: The serum PACAP levels of PD patients were significantly lower than those of healthy controls [(76.02 ± 43.78) pg/ml vs. (154.96 ± 76.54) pg/ml, P < 0.001]; and the serum VIP levels of PD patients were also significantly lower than those of healthy controls [(109.56 ± 15.39) pg/ml vs. (136.46 ± 24.16) pg/ml, P < 0.001]. PACAP levels were inversely correlated only with the score on NMSS item five, assessing Attention/memory (r = −0.276, P < 0.05) and lower serum PACAP levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [(61.87 ± 32.66) pg/ml vs. (84.51 ± 47.59) pg/ml, P < 0.05]; meanwhile, VIP levels were inversely correlated with the NMSS total score (r = −0.285, P < 0.05) and the single-item scores for item one, assessing Cardiovascular (r = −0.257, P < 0.05) and item three, assessing Mood/cognition (r = −0.373, P < 0.05), and lower serum VIP levels were detected in the anxiety subgroup and depression subgroup than in the non-anxiety subgroup and non-depression subgroup, respectively [(107.45 ± 15.40) pg/ml vs. (116.41 ± 13.67) pg/ml, P < 0.05]; [(104.45 ± 15.26) pg/ml vs. (113.43 ± 14.52) pg/ml, P < 0.05].Conclusion: The serum PACAP and VIP levels of PD patients were significantly lower than those of healthy controls. The non-motor symptoms significantly negatively correlated with serum PACAP level was cognitive dysfunction, while mood disorder was significantly correlated with serum VIP level.