Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.
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PMID:Regulation mechanisms of intestinal secretion: implications in nutrient absorption. 1198 1

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.
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PMID:Eating habits and appetite control in the elderly: the anorexia of aging. 1283 2

The neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) family of hormones exhibit a wide variety of biological actions on the mammalian gastrointestinal tract through known G-protein coupled receptor pathways. At least four receptor subtypes, denoted as Y(1), Y(2), Y(4) an Y(5), each with specific affinities to NPY ligands, serve as regulators of mucosal function, gastrointestinal motility and secretion. Investigations to date, however, have implicated the NPY peptides as mediators in the pathogenesis of numerous gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. Our understanding of these diseases and the interactions of NPY peptides have been advanced by the development of receptor agonists and antagonists that can be used experimentally in animal models. Potent selective PYY agonists have been developed that exhibit clinical potential as proabsorptive agents. NPY receptor agonists and antagonists as well as mice harboring null mutations in the Y(1) and Y(4) receptors have provided novel approaches in preventing intestinal inflammation and diarrhea. The use of competitive antagonists and Y(2) receptor knockouts have also aided in understanding secretory tone and electrogenic ion transport in the colon. In the pancreas, PYY suppresses amylase and cytokine release, which would be desirable in the clinical therapy of pancreatitis. Protein/DNA array analysis has revealed that PYY reduces transcription factor binding activity and disrupts signal transduction pathways activated by TNF-alpha in acinar cells. The present review gives an overview of NPY research in gastrointestinal disease and discusses its clinical relevance and potential use as therapy.
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PMID:NPY family of hormones: clinical relevance and potential use in gastrointestinal disease. 1797 80