The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders

https://www.gastrojournal.org/article/S0016-5085(04)01634-8/pdf

American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis

This literature review and the recommendations herein were prepared for the American Gastroenterological Association Clinical Practice Committee. The paper was approved by the Committee on May 16, 2004, and by the AGA Governing Board on September 23, 2004.

Technical review on the diagnosis and treatment of gastroparesis

Diets fed to nonruminant animals are composed mainly of feed ingredients of plant origin. A variety of antinutritional factors such as phytin, nonstarch polysaccharides, and protease inhibitors may be present in these feed ingredients, which could limit nutrients that may be utilized by animals fed such diets. The primary nutrient utilization-limiting effect of phytin arises from the binding of 6 phosphate groups, thus making the P unavailable to the animal. The negative charges allow for formation of insoluble phytin-metal complexes with many divalent cations. Furthermore, phytin and protein can form binary complexes through electrostatic links of its charged phosphate groups with either the free amino group on AA on proteins or via formation of ternary complexes of phytin, Ca(2+), and protein. The form and extent of de novo formation of binary and ternary complexes of phytin and protein are likely to be important variables that influence the effectiveness of nutrient hydrolysis in plant-based diets. Nonstarch polysacharides reduce effective energy and nutrient utilization by nonruminant animals because of a lack of the enzymes needed for breaking down the complex cell wall structure that encapsulate other nutrients. Enzymes are used in nonruminant animal production to promote growth and efficiency of nutrient utilization and reduce nutrient excretion. The enzymes used include those that target phytin and nonstarch polysaccharides. Phytase improves growth and enhances P utilization, but positive effects on other nutrients are not always observed. Nonstarch polysaccharide-hydrolyzing enzymes are less consistent in their effects on growth and nutrient utilization, although they show promise and it is imperative to closely match both types and amounts of nonstarch polysaccharides with appropriate enzyme for beneficial effects. When used together with phytase, nonstarch polysaccharide-hydrolyzing enzymes may increase the accessibility of phytase to phytin encapsulated in cell walls. The future of enzymes in nonruminant animal production is promising and will likely include an understanding of the role of enzyme supplementation in promoting health as well as how enzymes may modulate gene functions. This review is an attempt to summarize current thinking in this area, provide some clarity in nomenclature and mechanisms, and suggest opportunities for expanded exploitation of this unique biotechnology.

BOARD-INVITED REVIEW: opportunities and challenges in using exogenous enzymes to improve nonruminant animal production.

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain non-rheumatic conditions. It is available in a number of administration forms which can be given orally, rectally or intramuscularly. Conveniently, dosage adjustments are not required in the elderly or in those patients with renal or hepatic impairment. The drug has a relatively short elimination half-life, which limits the potential for drug accumulation. In numerous clinical trials the efficacy of diclofenac is equivalent to that of the many newer and established NSAIDs with which it has been compared. As an analgesic it has a fast onset and long duration of action. When administered intramuscularly it is at least comparable to, and frequently superior to, many narcotic and spasmolytic combinations in renal and biliary colic. Extensive clinical experience has been gained with diclofenac, clearly establishing its safety profile. It is well tolerated compared with other NSAIDs and rarely produces gastrointestinal ulceration or other serious side effects. Thus, diclofenac can be considered as one of the few NSAIDs of 'first choice' in the treatment of acute and chronic painful and inflammatory conditions.

Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy

https://www.gastrojournal.org/article/0016-5085(87)90976-0/pdf

Intravenous Cisapride Accelerates Delayed Gastric Emptying and Increases Antral Contraction Amplitude in Patients With Primary Anorexia Nervosa

In a double-blind trial, 12 out-patients with primary anorexia nervosa received, for six weeks, either 10 mg cisapride or placebo, three times a day. Cisapride accelerated gastric emptying of a radiolabelled semisolid meal in all six patients; five gained weight and symptoms of gastric retention ameliorated in four. With placebo, three of six had emptying enhanced, four gained weight, and one's symptoms improved. For another six weeks, all patients received cisapride. In five of the patients who had received cisapride, emptying further accelerated or remained stable; in one it slowed. Of the six patients who received placebo, four had emptying accelerated, five gained weight, and symptoms improved in four. Longer administration of cisapride may, by enhancing gastric motor activity, alleviate symptoms of retention and thus help to change eating behaviour.

Gastric emptying, body weight and symptoms in primary anorexia nervosa. Long-term effects of cisapride.

In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals.

https://gut.bmj.com/content/gutjnl/34/2/166.full.pdf

Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa.

Intravenous cisapride was shown to induce a phase-2-like pattern of human interdigestive jejunal motor activity containing an increased number of propagated contractions. This study investigated the effects of oral cisapride in 12 fasting healthy males. Jejunal pressures were recorded by a pneumohydraulic system and five catheter orifices positioned 10–30 cm aborad the ligament of Treitz. Single oral doses of 5 and 10mg cisapride, administered 5 min after an activity front under random double-blind conditions, induced a phase-2-like jejunal motor pattern with a significantly higher number and amplitude of contractions and significantly more aborally propagated waves than placebo (P<0.001), while the number of subjects with activity fronts decreased with increasing dose. Five and 10mg cisapride administered tid for three days affected psychomotor function, subjective feelings, and side-effect frequency, apart from increases in systolic blood pressure and heart rate, no more than placebo. It is concluded that in fasting man, oral cisapride induces a highly propagative phase-2-like jejunal motor pattern causing only minor side effects.

Effects of oral cisapride on interdigestive jejunal motor activity, psychomotor function, and side-effect profile in healthy man.

Previous studies showed that symptoms of oesophageal motor disorders can be misinterpreted as indicating anorexia nervosa and that in primary anorexia nervosa gastric motility is frequently impaired. We investigated in 32 women with bulimia nervosa whether symptoms of oesophageal motor disorders could be obscured by or be mistaken as forming part of bulimic behaviour, and whether impaired gastric motility was frequent as well. Oesophageal motility was normal in 18 of 26 patients studied, another four had incomplete lower oesophageal sphincter relaxation. Two patients had vigorous achalasia and each one achalasia and diffuse oesophageal spasm, all of whom experienced two types of vomiting: one self-induced and one involuntary, in which the vomit was non-acidic and tasted as the preceding meal. Gastric emptying of a semisolid meal was studied in all patients except of the eight with oesophageal motor abnormalities. Emptying was significantly slower than in healthy controls and grossly delayed in nine of 24 patients. Antral contraction amplitudes were lower and increased less postcibally than in controls. In conclusion (i) bulimic behaviour can obscure symptoms of oesophageal motor disorders and (ii) gastric emptying is frequently delayed in bulimia nervosa.

https://gut.bmj.com/content/gutjnl/31/3/259.full.pdf

G Gaupmann

Papers

Intravenous Cisapride Accelerates Delayed Gastric Emptying and Increases Antral Contraction Amplitude in Patients With Primary Anorexia Nervosa

Gastric emptying, body weight and symptoms in primary anorexia nervosa. Long-term effects of cisapride.

Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa.

Effects of oral cisapride on interdigestive jejunal motor activity, psychomotor function, and side-effect profile in healthy man.

Oesophageal and gastric motor activity in patients with bulimia nervosa.