Neuropeptide Modulation Enables Biphasic Internetwork Coordination via a Dual-Network Neuron.

Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing, often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crab Cancer borealis to investigate mechanisms of internetwork coordination, due to its small, well-characterized feeding-related networks (gastric mill [chewing, ∼0.1 Hz]; pyloric [filtering food, ∼1 Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric-plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG is necessary to shorten pyloric cycle period, likely through its rectified electrical coupling to pyloric pacemaker neurons. Hyperpolarizing current injections demonstrated that although LG bursting enables IC bursts, only gastric mill rhythm bursts in IC are necessary to prolong the pyloric cycle period. Surprisingly, LPG photoinactivation also eliminated prolonged pyloric cycles, without changing IC firing frequency or gastric mill burst duration, suggesting that pyloric cycles are prolonged via IC synaptic inhibition of LPG, which indirectly slows the pyloric pacemakers via electrical coupling. Thus, the same dual-network neuron directly conveys excitation from its endogenous bursting and indirectly funnels synaptic inhibition to enable one network to alternately decrease and increase the cycle period of a related network.

Effects of Lactobacillus rhamnosus GG on early postoperative outcome after pylorus-preserving pancreatoduodenectomy: a randomized trial.

OBJECTIVE: Pancreatoduodenectomy (PPPD) remains one of the most complex surgical procedures with high complication rates. Infectious complications, postoperative ileus and delayed gastric emptying in the perioperative period have a significant impact on the recovery from the treatment. Probiotics (PB) are known to have a beneficial effect as supportive therapy in major abdominal surgery but the evidence in pancreatic surgery is still limited. The aim of the study was to assess the influence of postoperative administration of PB on the early outcomes after PPPD. PATIENTS AND METHODS: Forty patients undergoing pylorus-preserving PPPD were enrolled to prospective trial and randomized in two groups: A - control group (n=20) receiving standard nutrition and B - probiotic group (n=20) treated additionally with Lactobacillus rahmnosus GG (L. rhamnosus GG) in the postoperative period from the day of the surgery for 30 days. Gastrointestinal motility, infection complications, length of hospital stay, and mortality were compared in the perioperative period and during 2 follow-up (i.e., after 14 and 30 days). RESULTS: There were no significant differences in mortality and infectious complications between groups. The length of hospital stay was shorter in the probiotic group compared to control (10 days vs. 8, respectively). The positive effect of L. rhamnosus GG on gastrointestinal tract's motility was observed, including earlier recurrence of postoperative bowel movements (group B: after 3.75 days vs. group A: 2.15 days), passing gasses (group B after 4 days vs. group A 2.9 days) and the first postoperative stool (group B after 5.84 days vs. group A 3.85 days). L. rhamnosus GG improved the appetite in postoperative day 1, 3, 5, 7 and 30 days after the surgery. CONCLUSIONS: L. rhamnosus GG improves the function of the gastrointestinal tract after major pancreatic surgery and may reduce the length of hospital stay.

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals.

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).

Endoscopic Botulinum toxin as a treatment for delayed gastric emptying following oesophagogastrectomy.

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

The gut-brain peptide neuromedin U (NMU) decreases food intake and body weight and improves glucose tolerance. Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose-dependent manner ex vivo in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c-FOS-positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.-Jarry, A.-C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.-N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

Intraoperative Pyloric Interventions during Oesophagectomy: a Multicentre Study.

BACKGROUND: Denervation of the pylorus after oesophagectomy is considered the principal factor responsible for delayed gastric emptying. Several studies have attempted to delineate whether surgical or chemical management of the pylorus during oesophagectomy is of benefit, but with conflicting results. The aim of this multicentre study was to assess whether there was any difference in outcomes between different approaches to management of the pylorus. METHODS: A prospectively maintained database was used to identify patients who underwent oesophagectomy for malignancy. They were divided into separate cohorts based on the specific pyloric intervention: intra-pyloric botulinum toxin injection, pyloroplasty and no pyloric treatment. Main outcome parameters were naso-gastric tube duration and re-siting, endoscopic pyloric intervention after surgery both as in- and outpatient, length of hospital stay, in-hospital mortality and delayed gastric emptying symptoms at first clinic appointment. RESULTS: Ninety patients were included in this study, 30 in each group. The duration of post-operative naso-gastric tube placement demonstrated significance between the groups (p = 0.001), being longer for patients receiving botulinum treatment. The requirement for endoscopic pyloric treatment after surgery was again poorer for those receiving botulinum (p = 0.032 and 0.003 for inpatient and outpatient endoscopy, respectively). CONCLUSION: We did not find evidence of superiority of surgical treatment or botulinum toxin of the pylorus, as prophylactic treatment for potential delayed gastric emptying after oesophagectomy, compared to no treatment at all. Based on our findings, no treatment of the pylorus yielded the most favourable outcomes.

Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities.

The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1ß in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases.

Is Chemical Pyloroplasty Necessary for Minimally Invasive Esophagectomy?

BACKGROUND: Many centers use botulinum toxin for chemical pyloroplasty in minimally invasive esophagectomies as prophylaxis against delayed gastric emptying. No previous studies have compared botulinum toxin injection with no pyloric intervention for patients treated with a combined laparoscopic and thoracoscopic approach. The authors hypothesized that chemical pyloroplasty does not improve outcomes for these patients. METHODS: The study investigated patients undergoing minimally invasive esophagectomies from September 2009 to June 2015. Delayed gastric emptying was defined as inability to tolerate a soft diet by postoperative day 10, as corroborated by esophagram, upper endoscopy, or both. Data were compared using Student's t test, χ 2 analysis, and Mann-Whitney U test where appropriate. RESULTS: The study identified 71 patients treated with minimally invasive esophagectomy: 35 patients with chemical pyloroplasty treated from September 2009 to January 2014 and 36 patients without pyloric intervention from February 2014 to June 2015. The groups were statistically similar in age, gender distribution, T stage, percentage of patients receiving neoadjuvant therapy, body mass index, preoperative weight loss, preoperative serum albumin, and preoperative placement of feeding tubes (all p > 0.05). The overall incidence of delayed gastric emptying was low in both groups: 8.6% (3/35) of the patients with chemical pyloroplasty versus 5.6% (2/36) of the patients with no pyloric intervention (p = 0.62). The two groups also did not differ significantly in the development of aspiration pneumonia or the need for pyloric intervention. CONCLUSIONS: In a well-matched cohort study with a historical control group, use of botulinum toxin for chemical pyloroplasty in minimally invasive esophagectomies was not associated with improved outcomes related to the pylorus versus no pyloric intervention. Although preliminary, these data suggest that chemical pyloroplasty is not necessary in minimally invasive esophagectomy.

Effect of endoscopic pyloric therapies for patients with nausea and vomiting and functional obstructive gastroparesis.

Gastroparesis (GP) is associated with loss of interstitial cells of Cajal (ICCs) and gastric dysrhythmias such as tachygastria. We hypothesized that a subset of patients with GP, normal 3cycles per minute (cpm) gastric myoelectrical activity (GMA), and normal upper endoscopy may respond to pyloric therapies. AIMS: To determine the effect of botulinum toxin A (btA) injection or balloon dilation (BD) of the pylorus on symptoms and body weight in patients with GP and 3cpm GMA. METHODS: Patients were identified who had GP, normal 3cpm GMA, and normal endoscopy that excluded mechanical obstruction of the pylorus. Electrogastrograms (EGG) with water load tests (WLT) were recorded to determine GMA. Gastric emptying was measured with 4h scintigraphy. Each patient underwent up to three pyloric treatments with btA or BD. RESULTS: Thirty-three patients (29 women) with an average age of 42years were studied. Seventy-nine percent had idiopathic GP and 21% had diabetic GP. The average percent meal retained at 4h was 42% and each EGG test showed normal 3cpm GMA. Nausea was the major symptom in 76% of patients. Complete or partial symptom response occurred in 75%, 72%, and 88% of patients after the first, second, or third endoscopic pyloric treatment, respectively. Overall, 78% of the 33 patients reported improvement in symptoms and average weight gain was 1.54lb from baseline to final treatment (p<0.04). CONCLUSION: Pyloric therapies appear to be effective treatments in symptomatic patients with GP and 3cpm GMA and controlled trials are warranted.

Nitric Oxide and Hydrogen Sulfide Interact When Modulating Gastric Physiological Functions in Rodents.

AIM: The objective was to evaluate the effects of nitric oxide (NO) and hydrogen sulfide (H2S) donors and possible interactions between these two systems in modulating gastric function. METHODS: Mice received saline, sodium nitroprusside (SNP), or sodium hydrosulfite (NaHS), and after 1 h, the animals were killed for immunofluorescence analysis of CSE or eNOS expressions, respectively. Other groups received saline, SNP, NaHS, Lawesson's reagent (H2S donor), PAG + SNP, L-NAME, L-NAME + NaHS, or L-NAME + Lawesson's reagent. Then, the gastric secretions (mucous and acid), gastric blood flow, gastric defense against ethanol, and gastric motility (gastric emptying and gastric contractility) were evaluated. RESULTS: SNP and NaHS increased the expression of CSE or eNOS, respectively. SNP or Lawesson's reagent did not alter gastric acid secretion but increased mucus production, and these effects reverted with PAG and L-NAME treatment, respectively. SNP or NaHS increased gastric blood flow and protected the gastric mucosa against ethanol injury, and these effects reverted with PAG and L-NAME treatments, respectively. SNP delayed gastric emptying when compared with saline, and PAG partially reversed this effect. NaHS accelerate gastric emptying, and L-NAME partially reversed this effect. SNP and NaHS alone induced gastric fundus and pylorus relaxation. However, pretreatment with PAG or L-NAME reversed these relaxant effects only in the pylorus but not in the gastric fundus. CONCLUSION: NO and H2S interact in gastric physiological functions, and this "cross-talk" is important in the control of mucus secretion, gastric blood flow, gastric mucosal defense, and gastric motility, but not in the control of basal gastric acid secretion.

Investigation of the effects of enteral hormones on the pyloric muscle in newborn rats.

PURPOSE: To investigate the effects of enteral hormones on pyloric muscle in order to clarify the etiopathogenesis of hypertrophic pyloric stenosis (HPS). METHODS: Forty-two newborn Wistar-Albino rats were included. No intervention was done in the control group (CG, n=6). In the sham group (SG, n=6) 1ml saline (0.9% NaCl solution), in the Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME) group (LNG, n=6) 100mg/kg/d L-NAME, in the somatostatin group (STG, n=6) 7mcg/kg/d ST, in the cholecystokinin group (CCKG, n=6) 3mcg/kg/d CCK, in the substance P group (SPG, n=6) 5ml/kg/d SP, and in the prostaglandin-E1 group (PGE1G, n=6) a cumulative dose of 360mcg/kg PGE1 was given intraperitoneally for 14days. On the 21st day, histopathological examination and muscle thickness measurements were done. Results were evaluated statistically. RESULTS: Total and circular pyloric muscle thicknesses were significantly increased in the LNG compared to the CG and SG (p<0.05). Circular pyloric muscle thickness was not increased in the STG, CCKG and SPG compared to the CG and SG (p>0.05). In the PGE1G, muscle thickness was significantly decreased in the pylorus and increased in the antrum compared to the CG and SG (p<0.05). CONCLUSION: Nitric oxide synthase (NOS) inhibition with L-NAME seems to be a causative factor in HPS by increasing pyloric muscle thickness. PGE predominantly affects antral gastric muscle and has no profound effect on pyloric muscle.

Double pylorus in a patient with Behçet's syndrome.

We report a patient with Behçet's syndrome who presented with upper gastrointestinal haemorrhage. Gastroduodenoscopy showed a gastroduodenal fistula which caused the appearance of double pylorus in the antrum. The possibility of peptic ulcer disease related to non-steroidal anti-inflammatory drug use or Behçet's syndrome itself, as the cause of this rare condition in this patient is discussed.

Coordination of distinct but interacting rhythmic motor programs by a modulatory projection neuron using different co-transmitters in different ganglia.

While many neurons are known to contain multiple neurotransmitters, the specific roles played by each co-transmitter within a neuron are often poorly understood. Here, we investigated the roles of the co-transmitters of the pyloric suppressor (PS) neurons, which are located in the stomatogastric nervous system (STNS) of the lobster Homarus americanus. The PS neurons are known to contain histamine; using RT-PCR, we identified a second co-transmitter as the FMRFamide-like peptide crustacean myosuppressin (Crust-MS). The modulatory effects of Crust-MS application on the gastric mill and pyloric patterns, generated in the stomatogastric ganglion (STG), closely resembled those recorded following extracellular PS neuron stimulation. To determine whether histamine plays a role in mediating the effects of the PS neurons in the STG, we bath-applied histamine receptor antagonists to the ganglion. In the presence of the antagonists, the histamine response was blocked, but Crust-MS application and PS stimulation continued to modulate the gastric and pyloric patterns, suggesting that PS effects in the STG are mediated largely by Crust-MS. PS neuron stimulation also excited the oesophageal rhythm, produced in the commissural ganglia (CoGs) of the STNS. Application of histamine, but not Crust-MS, to the CoGs mimicked this effect. Histamine receptor antagonists blocked the ability of both histamine and PS stimulation to excite the oesophageal rhythm, providing strong evidence that the PS neurons use histamine in the CoGs to exert their effects. Overall, our data suggest that the PS neurons differentially utilize their co-transmitters in spatially distinct locations to coordinate the activity of three independent networks.

Role of KATP channels and TRPV1 receptors in hydrogen sulfide-enhanced gastric emptying of liquid in awake mice.

Hydrogen sulphide (H(2)S) has shown to relax gastrointestinal muscle. Here in, we evaluated the effects of H(2)S donors on gastric emptying and in pyloric sphincter muscle relaxation, and whether these effects involved K(ATP) channels or TRPV1 receptors. Mice were treated with l-cysteine (alone or with propargylglycine-an inhibitor of H(2)S synthesis), NaHS, Lawesson's reagent (H(2)S donors) or saline. After 30 min, mice were gavaged with a liquid meal containing a nonabsorbable marker and then killed at 10, 20 or 30 min intervals to assess marker recovery from the stomach and intestine. This experiment was repeated in mice pre-treated with K(ATP) channel (glibenclamide) or TRPV1 receptor (capsazepine) antagonists. In addition, pyloric sphincter muscles were mounted in an organ bath, incubated with saline, glibenclamide or capsazepine, and NaHS dose-responses were determined. H(2)S donors and l-cysteine enhanced gastric emptying in a dose-dependent manner; propargylglycine reversed the effect of l-cysteine. Both glibenclamide and capsazepine abolished l-cysteine and H(2)S donors' augmentation of gastric emptying. Dose-dependent inductions of pyloric sphincter relaxation by NaHS were abolished by glibenclamide or capsazepine. These data suggest that H(2)S donors-induced acceleration of gastric emptying and relaxation of pyloric sphincter muscle by K(ATP) channel and TRPV1 receptor activations.

Restoration of descending inputs fails to rescue activity following deafferentation of a motor network.

Motor networks such as the pyloric network of the stomatogastric ganglion often require descending neuromodulatory inputs to initiate, regulate, and modulate their activity and their synaptic connectivity to manifest physiologically appropriate output. Prolonged removal of these descending inputs often results in a compensatory response that alters the inputs themselves, their targets, or both. Using the pyloric network of the crab, Cancer borealis, we investigated whether isolation of motor networks would result in alterations that change the responses of these networks to restored modulatory input. We used a reversible block with isotonic sucrose to transiently alter descending inputs into the pyloric network of the crab stomatogastric ganglion. Using this method, we found that blocking neuromodulatory inputs caused a reduced ability for subsequently restored modulatory projections to appropriately generate network output. Our results suggest that this could be due to changes in activity of descending projection neurons as well as changes in sensitivity to neuromodulators of the target neurons that develop over the time course of the blockade. These findings suggest that although homeostatic plasticity may play a critical role in recovery of functional output in a deafferented motor network, the results of these compensatory changes may alter the network such that restored inputs no longer function appropriately.

Endoscopic intrapyloric injection of botulinum toxin A in the treatment of children with gastroparesis: a retrospective, open-label study.

BACKGROUND: Botulinum toxin A has been used in children to treat spastic disorders and recently for GI conditions. Open-label studies in adults with gastroparesis have reported an improvement in symptoms and gastric emptying after endoscopic intrapyloric botulinum injections (IPBIs), although placebo-controlled trials have shown conflicting results. Only a single case report of IPBI is available in children. OBJECTIVE: To determine the long-term clinical outcomes and predictive factors for IPBI response in children with gastroparesis refractory to medical therapy. DESIGN: Retrospective review. SETTING: Single tertiary care center. PATIENTS: Children with refractory gastroparesis symptoms undergoing IPBIs. INTERVENTIONS: IPBIs. MAIN OUTCOME MEASUREMENTS: Clinical improvement and predictive factors for response. RESULTS: A total of 70 injections were given to 47 patients (mean age 9.98 ± 6.5 years; 23 female patients) with follow-up in 45 patients. IPBI failed in 15 patients and was successful in 30 patients. The median duration of response to the first IPBI was 3.0 months (95% CI, 1.2-4.8). A total of 29 patients received a single IPBI, and 18 received multiple IPBIs. Older age and vomiting predicted response to initial IPBI, and male sex predicted response to repeat IPBI. Only 1 patient reported exacerbation of vomiting after IPBI resolving within a week. LIMITATIONS: The open-label and retrospective nature of the study. CONCLUSION: IPBI is safe and may be effective in the management of children with symptoms of gastroparesis. Subgroups identifying who responded to the first IPBI include older patients and those presenting with vomiting, whereas male patients responded better to repeat IPBIs.

Role of 7,8-dimethoxycoumarin in anti-secretary and anti-inflammatory action on pyloric ligation-induced gastritis in rats.

The present study was designed to investigate the effect of 7,8-dimethoxycoumarin (DMC) isolated from ethyl acetate extract of Citrus decumana peels on gastritis in rats. Isolation of 7,8-DMC from ethyl acetate extract of C. decumana peels was done by column and preparative thin layer chromatography using different solvents on polarity basis. Furthermore, effect of 7,8-DMC (50, 75, and 100 mg/kg, i.p.) in pyloric ligation-induced gastritis was studied in rats. The highest dose of 7,8-DMC showed significant decrease in the gastric volume, total acidity, ulcerative index, thiobarbituric acid reactive species levels, and myeloperoxidase activity, whereas there was an increase in the glutathione level. However, the lowest and medium doses did not produce significant results as compared to omeprazole and N-acetyl cysteine-treated groups. Compound 7,8-DMC (100 mg/kg) showed ameliorative effect on gastric inflammation and may be used as a therapeutic agent in the treatment of gastritis.

Cell specific dopamine modulation of the transient potassium current in the pyloric network by the canonical D1 receptor signal transduction cascade.

Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, by directly acting on each of the circuit neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels (I(A)) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of I(A) in opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of I(A) is unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP I(A) were due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP I(A) was mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP I(A) was blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on I(A) are due to differences in receptor expression.

Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity.

AIM: To observe the effects of traditional antiinflammatory medicine Lonicerae Flos (LF) on rat reflux esophagitis (RE) induced by pylorus and forestomach ligation compared with the well-known proton antioxidant, alpha-tocopherol. METHODS: Rats were pretreated with three different dosages of LF (500, 250 and 125 mg/kg) orally, once a day for 14 d before pylorus and forestomach ligation. Nine hours after pylorus and forestomach ligation, changes to the stomach and esophagus lesion areas, gastric volumes, acid and pepsin outputs, antioxidant effects, esophageal lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), myeloperoxidase and glutathione (GSH) levels, and collagen contents (marker of flexibility) were observed on the esophageal and fundic histopathology. The results were compared with an alpha-tocopherol (once orally, 1 h before operation, 30 mg/kg) treated group in which the effects on RE were already confirmed. RESULTS: Pylorus and forestomach ligations caused marked increases of gross esophageal and gastric mucosa lesion areas, which corresponded with histopathological changes. In addition, increases of esophageal lipid peroxidation, decreases of SOD, CAT, and GSH-free radical scavengers, increases of collagen were observed. However, these pylorus and forestomach ligation induced RE were dose-dependently inhibited by treatment of 500, 250 and 125 mg/kg of LF extract, mediated by antioxidant effects. RE at 250 mg/kg showed similar effects alpha-tocopherol. CONCLUSION: The results suggest that antioxidant effects of LF could attenuate the severity of RE and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.