Changes In Gastric Function Research Articles

A central amygdala input to the dorsal vagal complex controls gastric motility in mice under restraint stress.

Background/aims: Psychological and physiological stress can cause gastrointestinal motility disorders. Acupuncture has a benign regulatory effect on gastrointestinal motility. However, the mechanisms underlying these processes remain unclear. Methods: Herein, we established a gastric motility disorder (GMD) model in the context of restraint stress (RS) and irregular feeding. The activity of emotional center-central amygdala (CeA) GABAergic neurons and gastrointestinal center-dorsal vagal complex (DVC) neurons were recorded by electrophysiology. Virus tracing and patch clamp analysis of the anatomical and functional connection between the CeAGABA → dorsal vagal complex pathways were performed. Optogenetics inhibiting or activating CeAGABA neurons or the CeAGABA → dorsal vagal complex pathway were used to detect changes in gastric function. Results: We found that restraint stress induced delayed gastric emptying and decreased gastric motility and food intake. Simultaneously, restraint stress activated CeA GABAergic neurons, inhibiting dorsal vagal complex neurons, with electroacupuncture (EA) reversing this phenomenon. In addition, we identified an inhibitory pathway in which CeA GABAergic neurons project into the dorsal vagal complex. Furthermore, the use of optogenetic approaches inhibited CeAGABA neurons and the CeAGABA → dorsal vagal complex pathway in gastric motility disorder mice, which enhanced gastric movement and gastric emptying, whereas activation of the CeAGABA and CeAGABA → dorsal vagal complex pathway mimicked the symptoms of weakened gastric movement and delayed gastric emptying in naïve mice. Conclusion: Our findings indicate that the CeAGABA → dorsal vagal complex pathway may be involved in regulating gastric dysmotility under restraint stress conditions, and partially reveals the mechanism of electroacupuncture.

951 Association Between Risk Factors for Constipation and Severity of Stool Retention As Analyzed By Abdominal X-Ray

Introduction:Upper gastrointestinal function may change over time in healthy or impaired motility patient groups. Identifying any physiological changes of the GI tract as it ages would be important in order to classify true GI malfunction in older populations. The SmartPill capsule (SP) can do this by measuring the gastric emptying time (GET) and record the GI intraluminal pressures non-invasively. Aim:To determine if gastric function changes over time in healthy subjects and patients with gastroparesis (GP). Methods:Healthy (GET>5h) and GP (GET 3units above gastric pH. Healthy and GP subjects were each divided into age groups: age>65 and age 65y.o. was significantly slower than subjects 0.3) or after GET (p>0.4). In the comparison of subgroups, there was no significant difference in GET between quartiles (p>0.1) except Q1 had a significantly faster GET than Q4. In the 42 GP subjects, there was no significant difference in GET between subjects >65y.o. and 0.06) or after GET (p>0.1). Conclusion:The GET of subjects over the age of 65 is slower than subjects between the ages of 19-34 in the healthy population. There appears to be no difference in GET among the other age groups, as well as no difference in GI contractility. The increase of delayed GET with age should be taken into consideration in drug development that may use younger populations to assess drug efficacy. The normal range of delayed gastric emptying in patients over the age of 65 may have to be extended as it may increase with age.

949 Impact of Age On Upper Gastrointestinal Function in Healthy and Gastroparetic Populations, As Measured By a Non-Invasive Wireless Capsule

Introduction:Upper gastrointestinal function may change over time in healthy or impaired motility patient groups. Identifying any physiological changes of the GI tract as it ages would be important in order to classify true GI malfunction in older populations. The SmartPill capsule (SP) can do this by measuring the gastric emptying time (GET) and record the GI intraluminal pressures non-invasively. Aim:To determine if gastric function changes over time in healthy subjects and patients with gastroparesis (GP). Methods:Healthy (GET>5h) and GP (GET 3units above gastric pH. Healthy and GP subjects were each divided into age groups: age>65 and age 65y.o. was significantly slower than subjects 0.3) or after GET (p>0.4). In the comparison of subgroups, there was no significant difference in GET between quartiles (p>0.1) except Q1 had a significantly faster GET than Q4. In the 42 GP subjects, there was no significant difference in GET between subjects >65y.o. and 0.06) or after GET (p>0.1). Conclusion:The GET of subjects over the age of 65 is slower than subjects between the ages of 19-34 in the healthy population. There appears to be no difference in GET among the other age groups, as well as no difference in GI contractility. The increase of delayed GET with age should be taken into consideration in drug development that may use younger populations to assess drug efficacy. The normal range of delayed gastric emptying in patients over the age of 65 may have to be extended as it may increase with age.

950 Assessment of Colonic, Whole Gut and Regional Transit in Elderly Constipated and Healthy Subjects with a Novel Wireless pH/Pressure Capsule (SmartPill®)

Introduction:Upper gastrointestinal function may change over time in healthy or impaired motility patient groups. Identifying any physiological changes of the GI tract as it ages would be important in order to classify true GI malfunction in older populations. The SmartPill capsule (SP) can do this by measuring the gastric emptying time (GET) and record the GI intraluminal pressures non-invasively. Aim:To determine if gastric function changes over time in healthy subjects and patients with gastroparesis (GP). Methods:Healthy (GET>5h) and GP (GET 3units above gastric pH. Healthy and GP subjects were each divided into age groups: age>65 and age 65y.o. was significantly slower than subjects 0.3) or after GET (p>0.4). In the comparison of subgroups, there was no significant difference in GET between quartiles (p>0.1) except Q1 had a significantly faster GET than Q4. In the 42 GP subjects, there was no significant difference in GET between subjects >65y.o. and 0.06) or after GET (p>0.1). Conclusion:The GET of subjects over the age of 65 is slower than subjects between the ages of 19-34 in the healthy population. There appears to be no difference in GET among the other age groups, as well as no difference in GI contractility. The increase of delayed GET with age should be taken into consideration in drug development that may use younger populations to assess drug efficacy. The normal range of delayed gastric emptying in patients over the age of 65 may have to be extended as it may increase with age.

Gastric outlet obstruction as a consequence of a duodenal web masquerading as gastrinoma in an adult

Abstract We present the case of a 24-year-old man with recurrent peptic ulcers and hypergastrinemia, in whom a multidisciplinary investigation for gastrinoma revealed a duodenal web. The affected duodenal segment was excised, and a gastroduodenostomy with highly selective vagotomy was performed. Postoperative serum gastrin levels returned to the normal range over the next 6 weeks. Congenital duodenal anomalies are unusual causes of gastric outlet obstruction in adults. Chronic gastric outlet obstruction secondary to an adult duodenal web can induce neurohumoral changes in gastric function, which enhance both acid output and gastrin secretion. This case reminds clinicians to consider congenital anomalies in adults presenting with recurrent peptic ulcers and hypergastrinemia.

LPS-induced suppression of gastric motility relieved by TNFR:Fc construct in dorsal vagal complex.

Our previous studies suggested that the cytokine tumor necrosis factor-alpha (TNF-alpha) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function, such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF-alpha is capable of affecting gastric function via the DVC circuitry has been impeded by the lack of an antagonist for TNF-alpha. The present studies used localized central nervous system applications of the TNF-adsorbant construct (TNFR:Fc; TNF-receptor linked to the Fc portion of the human immunoglobulin IgG1) to attempt to neutralize the suppressive effects of endogenously produced TNF-alpha. Gastric motility of thiobutabarbital-anesthetized rats was monitored after systemic administration of lipopolysaccharide (LPS) to induce TNF-alpha production. Continuous perfusion of the floor of the fourth ventricle with TNFR:Fc reversed the potent gastroinhibition induced by LPS, i.e., central thyrotropin-releasing hormone-induced increases in motility were not inhibited. This disinhibition of gastric stasis was not seen after intravenous administration of similar doses of TNFR:Fc nor ventricular application of the Fc fragment of human immunoglobulin. These results validate our previous studies that suggest that circulating TNF-alpha may act directly within the DVC to affect gastric function in a variety of pathophysiological states.

Postprandial normal saline intake delays gastric emptying of solids in conscious dogs: partial involvement of CCK in its mechanism.

Although it is known that a caloric liquid meal given after food intake delays solid gastric emptying, the effect of a noncaloric liquid is not known. The aims of this study were to determine the effect of normal saline given at 3 hr after feeding on gastric antral motor activity and gastric emptying and to evaluate the role of endogenous cholecystokinin in the changes in gastric function induced by postprandial saline intake in conscious dogs. Two cannulas were implanted in each of five mongrel dogs for infusion of phenolsulfonphthalein into the proximal duodenum and for aspiration of luminal samples from the distal duodenum. Gastric contractile and emptying activity were measured by the force transducer method and a freeze-drying method newly developed by our group, respectively. Postprandial pancreaticobiliary secretion was assessed from amylase and bile acid outputs into the duodenum. One hundred grams of freeze-dried dog food was given as a solid meal after mixing it with 100 ml of normal saline. The dogs were given 100 ml of normal saline per os at 3 hr after feeding. In another study, intravenous administration of devazepide, a specific cholecystokinin-A receptor antagonist, at a dose of 0.1 mg/kg/hr was begun 15 min before postprandial saline intake and continued for 1 hr. Gastric antral motility was significantly (P < 0.01) inhibited for 30 min after the dogs had drunk saline at 3 hr after feeding. The mean fractional emptying rate of gastric solids in percentage per 30 min after postprandial saline intake was significantly (P < 0.05) slower than that in the control study without saline intake at 3 hr after feeding. Amylase output into the duodenum after postprandial saline intake showed a gradual increase lasting for about 1 hr, whereas that of bile acid increased transiently but markedly 15 min after saline intake, in comparison with the control study. Pretreatment with devazepide partially ameliorated the suppression of gastric antral motility. Postprandial intake of saline inhibited gastric motor activity and delayed solid gastric emptying, whereas it increased the outputs of amylase and bile acid. Endogenous cholecystokinin may be partially involved in these phenomena caused by saline intake at 3 hr after feeding.

Role of the sympathetic nervous system in gastric functional changes induced by thyrotropin-releasing hormone in rats.

We determined the changes in gastric functions and systemic blood pressure in response to thyrotropin-releasing hormone (TRH) simultaneously in anesthetized rats and examined the role of the sympathetic nervous system in these changes. TRH injected i.c. increased gastric acid secretion, contraction and mucosal blood flow, and produced hemorrhagic lesions in the glandular stomach. These responses to TRH were almost completely inhibited by bilateral cervical vagotomy or atropine. The increased gastric acid secretion and contraction in response to TRH were significantly augmented by pretreatment with yohimbine but not with prazosin. Bilateral adrenalectomy also potentiated the gastric acid secretory and contractile responses to TRH. Neither prazosin, yohimbine nor adrenalectomy had any appreciable effect on the increased gastric mucosal blood flow induced by TRH. TRH-induced gastric mucosal lesions were significantly aggravated by yohimbine and adrenalectomy. In vagotomized rats, TRH significantly suppressed the gastric functional changes induced by electrical stimulation of the vagus nerves. These data suggest that while gastric functional changes and mucosal lesions induced by TRH mainly occur through stimulation of the vagus nerves, these responses are extensively modified by the sympathetic nervous system including the adrenal glands.

Changes in Gastric Function and Healing of Chronic Gastric Ulcers in Aged Rats

The present study was designed to determine the relationship between changes in gastric function caused by aging and the healing of gastric ulcers. Male Fischer-344 rats (young, 2 months; aged, 24–26 months) were used. Gastric ulcers were induced by luminal application of an acetic acid solution (60%, 0.2 ml, 45 sec). The basal and histamine-stimulated gastric acid secretions in aged animals were significantly lower than those in young animals. However, the serum gastrin levels were almost the same in the two groups. Gastric mucosal blood flow and mucosal cell proliferation were also decreased in aged animals. Gastric contractile activity induced by electrical vagal stimulation was almost the same in the two groups, while the gastric relaxative response was significantly reduced in aged animals. The development and healing rate of gastric ulcers in aged animals were almost the same as those in young animals. Histologically, regeneration of the ulcerated mucosa was significantly reduced and tissue contraction occurred in aged animals, as compared to in young animals. We concluded that aging had little or no influence on the development and healing rate of gastric ulcers in rats, but the quality of ulcer healing was quite different between young and aged animals, probably resulting from various gastric dysfunctions related to ulcer healing.

Changes in Gastric Function During Healing of Gastric Ulcers

Abstract: To determine changes in pathophysiology during the healing process of gastric ulcers, gastric acid secretion, gastric emptying, fasting gastrin levels (FGL) and the integrated gastrin response (IGR) were studied in normal volunteers and in each stage of gastric ulcers. In a study of patients with gastric ulcers in the lesser curvature of the ventricular angulus including 20 in the active stage, 49 in the healing stage and 11 in the healed (scar) stage, gastric acid secretion (BAO and MAO) and FGL gradually decreased as the patients progressed from the active stage through the healing and healed stages. IGR values did not change, but gastric emptying showed marked prolongation in the active and healing stages although this was alleviated in the healed stage. In 11 of the same gastric ulcer patients who were followed up, gastric acid secretion, especially BAO, was lower in the healed stage than in the active stage. No fixed tendency was seen for gastric emptying and IGR, but FGL showed higher values in the active stage than in the healing stage. These findings indicated that changes in the pathophysiology of the stomach occur during the healing of gastric ulcers, and it was assumed that these changes are closely related to the stage of the ulcer.

Cold exposure elevates thyrotropin-releasing hormone gene expression in medullary raphe nuclei: Relationship with vagally mediated gastric erosions

The stimulation of thyrotropin release by cold is associated with an increase in thyrotropin-releasing hormone gene expression in the paraventricular nucleus of the hypothalamus. Cold exposure also stimulates autonomic outflow to viscera. There is evidence that caudal raphe nuclei are involved in autonomic regulation through thyrotropin-releasing hormone projections to the dorsal vagal complex and spinal cord. To determine whether cold modulates thyrotropin-releasing hormone gene expression in the caudal raphe nuclei, the effect of cold exposure on thyrotropin-releasing hormone messenger RNA levels in the rat lower brainstem was examined by quantitative Northern blot analysis and thyrotropin-releasing hormone messenger RNA was localized by in situ hybridization. The gastric responses to cold exposure were also assessed in sham or vagotomized rats with pylorus ligation. Thyrotropin-releasing hormone messenger RNA signal was detected in the RNA extracted from the medulla and hypothalamus but not from the amygdala, periaqueductal gray or cerebellum. Cold exposure (4°C) for 1 or 3 h increased thyrotropin-releasing hormone messenger RNA levels in the medulla by77 ± 37 and142 ± 39% respectively. In situ hybridization histochemistry showed that the increase in silver grain density occurred exclusively in the raphe pallidus and raphe obscurus. Exposure to cold stress for 2 h stimulated gastric acid secretion and resulted in gastric lesion formation in sham but not vagotomized rats. There are established thyrotropin-releasing hormone projections from the raphe pallidus and obscurus to the dorsal vagal complex. Thyrotropin-releasing hormone is known to exert an excitatory effect on neurons of the dorsal motor nucleus of the vagus, leading to vagally mediated stimulation of gastric function and erosions. The increased thyrotropin-releasing hormone gene expression in the raphe pallidus and obscurus induced by cold supports an important role of endogenous thyrotropin-releasing hormone contained in caudal raphe nuclei-dorsal vagal complex pathways in vagally mediated changes in gastric function induced by cold.

Opposing gastric motor responses to TRH and substance P on their microinjection into nucleus raphe obscurus of rats.

Little is known about the functional role of putative neurotransmitters in the nucleus raphe obscurus (NRO) in the control of gastric motor function, although thyrotropin-releasing hormone (TRH) and substance P (SP) have been detected in the cell bodies and/or fibers of this nucleus. Therefore, we investigated the effects of microinjection of these peptides (in a volume of 60 nl) into the caudal NRO of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature motility, and blood pressure. L-Glutamate (30 nmol) was first microinjected into the NRO to identify the "gastric" region of the NRO and elicited significant increases in intragastric pressure as well as pyloric and greater curvature motility in all 16 animals. TRH (2-45 pmol, n = 16) microinjected into the same sites increased intragastric pressure as well as pyloric and greater curvature motility, and these effects were abolished by bilateral cervical vagotomy and atropine (0.5-1.0 mg/kg iv) but not by spinal cord transection. Microinjection of SP (45-405 pmol, n = 15) into the same sites decreased intragastric pressure; however, the inhibitory effect of SP on pyloric and greater curvature motility did not attain statistical significance. The effect of SP on intragastric pressure was completely abolished by bilateral vagotomy but not by systemic administration of atropine (1 mg/kg) or spinal cord transection. Microinjections of 45 pmol TRH and 405 pmol SP just outside of the NRO did not result in changes in gastric function. No overall significant changes in blood pressure were noted after microinjection of L-glutamate, TRH, or SP into the gastric region of the NRO. We conclude that both TRH and SP affect gastric motor function in the caudal NRO via a vagally mediated pathway; TRH apparently activates vagal cholinergic pathways, but the mechanism of SP-evoked gastric motor inhibition remains to be further investigated.

P-57 - Mechanisms of gastric functional changes induced by intragastric administration of N-ethylmaleimide (NEM) in rats.

P-57 - Mechanisms of gastric functional changes induced by intragastric administration of N-ethylmaleimide (NEM) in rats.

O-164 - Modification of TRH induced gastric functional changes by sympathetic nervous, prostaglandins and nitric oxide in rats.

O-164 - Modification of TRH induced gastric functional changes by sympathetic nervous, prostaglandins and nitric oxide in rats.

Aspirin-induced changes in gastric function: Role of endogenous prostaglandins and mucosal damage

The relative roles of prostaglandins and mucosal injury in aspirin-induced changes in gastric function were evaluated. Conscious rhesus monkeys received a subcutaneous injection of sodium bicarbonate or aspirin (25, 50, 100, or 150 mg/kg) and sodium bicarbonate or 150 mg/kg aspirin subcutaneously plus oral sucralfate (25 mg/kg twice a day). Gastric emptying and fluid and H+ outputs were determined during a fasting period and after an 80-ml water load using a 99mTc-diethyIenetriaminepentaacetic acid dilution technique. At the end of each study, the monkeys were gastroscoped to assess mucosal damage, which was ranked blindly on a scale of 0 to 5. Biopsy samples were taken from antrum and fundus for determination of prostaglandins and histological evaluation. All doses of aspirin significantly suppressed prostaglandins in both the antrum and fundus. In contrast, the aspirin-induced increase in gastric mucosal injury was dose dependent. Aspirin also produced a dose-dependent decrease in gastric emptying that was significantly correlated with erosions scores. When aspirin-induced lesions were prevented by sucralfate, the inhibition of gastric emptying was blocked during the fasting period and was attenuated following the water load. Acid secretion was also decreased significantly by aspirin. This action was not modified by sucralfate protection, suggesting that aspirin has a direct inhibitory effect on parietal cell secretion. These data show that mucosal damage contributes significantly to the aspirin-induced changes in gastric function. Moreover, prostaglandins may play a role in the control of gastric emptying, especially during early phase of the response to a water load.

Fever, anorexia and forestomach hypomotility in ruminants.

Acute febrile diseases are characterized by specific and non-specific symptoms. The non-specific responses include among other signs fever, dullness, anorexia and changes in gastric function. It is the purpose of this review to describe present concepts of fever and the associated reactions produced by bacterial pyrogens and the mechanisms of those reactions. The available data indicate that interleukin-1 is a key mediator of host responses to bacterial infections. However, many questions have not yet been clearly answered. In particular, more detailed studies of the processes within the CNS responsible for anorexia are still required.

Fever and associated clinical haematologic and blood biochemical changes in the goat and other animal species

Summary Acute febrile diseases are characterized by specific and non-specific symptoms. The non-specific responses are presented under the headings: fever, inflammation and pain, experimental models for investigating febrile reactions, haematologic changes, blood biochemical changes, cardiovascular effects, changes in gastric function, and the effects of fever upon pharmacokinetics of drugs. It was the purpose of this review to describe present concepts of thermoregulation and fever, the associated reactions produced by bacterial pyrogens and the mechanisms of these reactions. The available data illustrate, that many questions have not yet been clearly answered. However, the entire field of research involving endogenous substances, such as interleukin-1, is now moving ahead with great speed. Furthermore, there is some evidence which suggests that fever and the associated lower plasma zinc and iron levels act together as a co-ordinated non-specific host defence mechanism. Since experimental fever has a distinct effect upon the pharmacokinetics of drugs, more attention should be given to this aspect.

Relationship between diseases of the pancreas and hyperplasia of Brunner's glands

Examination of 105 duodeno-pancreatectomy specimens showed that 75% of the cases of chronic pancreatitis (n = 74) manifested diffuse hyperplasia of Brunner's glands. In pancreatitis involving part of the pancreas in the presence of ducts of the embryonic type (n = 6), in segmental pancreatitis (n = 16), and in pancreatic cancer (n = 23), no significant difference in the thickness of the layer of Brunner's glands was found as compared with normal specimens. There was no statistically significant correlation between the degree of hyperplasia of Brunner's glands and the degree of scarring of the exocrine pancreatic parenchyma. Nor was there any correlation between existence and extent of scarring of the duodenal wall, inflammatory infiltration of the duodenal mucosa, duration of disease, consumption of alcohol and history of gall stones and ulcers in patients with and without hyperplasia of Brunner's glands. Diffuse hyperplasia of the duodenal glands is probably an adaptive reaction to the exocrine insufficiency of the pancreas or the changes in gastric function (hyperacidity, accelerated emptying of the stomach) caused by chronic pancreatitis. A fact which supports this statement is that the inhibitor hormone urogastrone--an inhibitor of gastric acid secretion--is formed in Brunner's glands. The question is also discussed whether chronic pancreatitis and hyperplasia of Brunner's glands might not also develop simultaneously in the presence of disturbances of the gastrointestinal hormones, themselves either primary or due to alcohol consumption.

Studies in headache mechanisms.

Introduction Headache may be the commonest complaint heard in physicians' offices. The great majority of headaches are linked either with cranial vasodilatation or skeletal muscle contraction and cranial vasoconstriction. The former are called migraine; the latter, muscle-contraction headache.1Changes in gastric function, feeling state, nasal function, fluid and electrolyte excretion, cardiac rhythm, and body temperature regulation may occur in association with headache Fig. 1.—Cranial artery pulse wave recorder. attack. A part of our newer knowledge of migraine headache phenomenology is herein reviewed. Fig. 2.—Poser slit lamp and camera attachment for study of bulbar conjunctival vessels. Headache mechanisms were studied with use of the devices shown in Figures 1 and 2. Fig. 3.—Effect of topical acetylcholine on bulbar conjunctival vessels. Contrast the normal vessels at the top with the minimal dilatation (sensitivity) at bottom. Fig. 4.—Effect of topical levarterenol on bulbar conjunctival vessels. Those at the top are normal. At