Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A greater understanding of the various serotonin receptor subtypes has led to a clearer appreciation of the role of serotonin in gastrointestinal motility, sensation and secretion. Serotonin is definitely involved in the aetiopathogenesis of cisplatin-induced emesis and carcinoid diarrhoea. The application of serotonergic drugs in clinical therapeutics for gut disturbances is presently dominated by the use of 5-HT3 antagonists for acute chemotherapy-induced nausea and vomiting, and the use of substituted benzamides which are 5-HT4 agonists stimulating gut motor function through 5-HT4 neuronal receptors. The best-studied 5-HT4 agonist is cisapride, which has been shown to stimulate motility at several levels of the gut. Cisapride is approved for healing and maintenance treatment of reflux oesophagitis and is used in several countries for the alleviation of symptoms consistent with regional stasis, from dyspepsia to constipation. Carcinoid diarrhoea is a prototypic disease associated with deranged serotonin metabolism, and a rationale for using 5-HT3 or 5-HT4 antagonists is based on the recent appreciation of the important role of impaired gut motor function in carcinoid diarrhoea. In the future, greater understanding of the serotonin receptor subtypes and their role in gut disorders may lead to novel approaches to alleviate increased visceral perception of functional gastrointestinal disorders, to correct changes in colonic capacitance, or to alter gastrointestinal motility that contributes to diarrhoea or constipation. However, at the present time, it must be stressed that these uses are still at an experimental stage and that careful validation and proper controlled studies are still required.
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PMID:Drugs affecting serotonin receptors. 794 60

Although physiological stimuli in the healthy gastrointestinal tract are generally not associated with conscious perception, chronic abdominal discomfort and pain are the most common symptoms resulting in patient visits with gastroenterologists. Symptoms may be associated with inflammatory conditions of the gut or occur in the form of so-called functional disorders. The majority of patients with functional disorders appear to primarily have inappropriate perception of physiological events and altered reflex responses in different gut regions. Recent breakthroughs in the neurophysiology of somatic and visceral sensation are providing a series of plausible mechanisms to explain the development of chronic hyperalgesia within the human gastrointestinal tract. A central concept to all these mechanisms is the development of hyperexcitability of neurons in the dorsal horn, which can develop either in response to peripheral tissue irritation or in response to descending influences originating in the brainstem. Taking clinical characteristics and the concept of central hyperexcitability into account, a model is proposed by which abdominal pain from chronic inflammatory conditions of the gut and functional bowel disorders such as noncardiac chest pain, nonulcer dyspepsia, and irritable bowel syndrome could develop by multiple mechanisms either alone or in combination.
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PMID:Basic and clinical aspects of visceral hyperalgesia. 783 12

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.
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PMID:Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. 809 58

In clinical practice, exogenous pancreatic enzymes are administered for the treatment of pancreatogenic steatorrhea or with the intention to relieve pain due to chronic pancreatitis. Moreover, a large number of patients take pancreatin (i.e., exogenous pancreatic enzymes) for functional dyspepsia. The effect of exogenous pancreatic enzymes on the enteropancreatic axis is a complex issue. Intraduodenal but not intrajejunal protease activity appears to exert a dose-dependent negative feedback on exocrine pancreatic secretion. Only enzymes with a proteolytic activity but not amylase and lipase exert a control on pancreatic secretion. The mechanism responsible for this feedback regulation is debated, but the cholinergic system seems to play a major role. Intraduodenal pancreatic enzymes (pancreatin) lead to an increased release of pancreatic polypeptide but do not affect the release of insulin and glucagon. In addition, pancreatic enzymes have an influence on the release of some gastrointestinal hormones (i.e., cholecystokinin, motilin, gastric inhibitory polypeptide). Neither exogenous nor endogenous pancreatic enzymes seem to play a major role in the regulation of interdigestive gastrointestinal motility. However, an adequate rate of postprandial pancreatic output is required to control gastric emptying. Current knowledge on the effect of exogenous pancreatic enzymes on the enteropancreatic axis, gut peptide release and gastrointestinal motility are updated in the present article.
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PMID:Effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility. 822 68

Cholecystokinin (CCK) belongs to the group of substances known as brain-gut peptides: it functions both as a neuropeptide and a gut hormone. The peptide and its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart caerulein) significantly delay emptying of gastric contents in both animals and humans. The fact that CCK, in doses mimicking postprandial plasma levels, strongly affects emptying rate suggests the peptide to be a physiologic regulator of gastric emptying. Unfortunately, clear definition of the role of CCK in the physiology of gastric motor activity has long been hampered by the lack of specific and potent non-peptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and examination of its putative role in certain diseases. This paper summarizes the available data concerning the effect of CCK and its antagonists on gastric emptying. The use of selective CCK-antagonists has allowed to establish that the gastric motor effect of the peptide is direct and mediated through the stimulation of CCK-A receptors. As a consequence, CCK-A antagonism results in acceleration of emptying rate under certain experimental and clinical conditions. This peculiar pharmacologic effect of CCK-A antagonists, which could be useful in the treatment of functional dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux disease (where patients often display a delayed emptying rate of solid food) needs to be further investigated, in order to fully explore their potential as gastrokinetic drugs.
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PMID:Effect of CCK and its antagonists on gastric emptying. 829 6

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'.
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PMID:Functional gastrointestinal disorders in unselected patients with non-cardiac chest pain. 836 9

We studied gastric motor functions by scintigraphic gastric emptying analysis and surface electrogastrography (EGG), and personality trait deviation in patients with functional dyspepsia. Delayed gastric emptying was observed in 17/35 patients and reduced normal EGG activity in 22/35 functional dyspepsia patients. There was a highly significant negative correlation between the gastric retention rate (at 150 min) and the duration of normal EGG waves. Abnormally high T scores on the Minnesota Multiphasic Personality Inventory (MMPI) test (70 or above) were found in 14/21 patients. Hypochondriasis (Hs) and conversion hysteria (Hy) were the most common abnormal findings. Ninety percent of functional dyspepsia patients (19/21) had either gastric dysmotility and/or psychological deviation. Although there was no significant correlation between gastric dysmotility and deviation in personality traits in functional dyspepsia patients, these data suggest that brain-gut interactions may play an important role in the symptoms of functional dyspepsia.
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PMID:Personality deviation and gastric motility in patients with functional dyspepsia. 877 15

The pathophysiology of functional gastro-intestinal disorders remains unclear. A relatively new approach to these disorders has been the study of visceral sensory perception. A decreased pain threshold to intraluminal balloon distension has been demonstrated in patients with irritable bowel syndrome, functional dyspepsia, and non-cardiac chest pain. This altered visceral sensitivity does not appear to extend to somatic sensation; patients have generally had normal sensory thresholds to various stimuli applied to the skin. It is uncertain whether altered gut sensation represents a primary event in the pathogenesis of disease or simply a disease marker. In this review, we examine the evidence of altered visceral sensation and discuss the implications for patient management and drug therapy.
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PMID:Visceral perception in functional gastro-intestinal disorders: disease marker or epiphenomenon? 890 13

Gastrointestinal prokinetics promote or increase the coordination of the gut wall contractions leading to enhancement of propulsive motility and, consequently, caudal displacement of luminal contents. Currently, they are considered drugs of choice for the treatment of upper gastrointestinal tract functional motor disorders such as those associated with gastrooesophageal reflux disease, chronic dyspepsia, gastroparesis (idiopathic or secondary to other diseases) and acute or chronic idiopathic intestinal pseudo-obstruction. The aim of the present review is to give an outline of the pharmacology of currently available prokinetics and of novel drugs endowed with gastrointestinal prokinetic action that require further pharmacological and/or clinical testing. The novel drugs include recent generations of benzamide and non-benzamide 5-HT4 receptor agonists, motilin receptor agonists, and inhibitors of nitric oxide synthase. Furthermore, based on our improved knowledge of the role of 5-HT in emesis and gastrointestinal motility, the therapeutic potential of potent mixed 5-HT4 agonists--5-HT3 antagonists in the control of cytotoxic-drug-induced emesis and associated gut motor disturbances will be discussed. Lastly, a section of this review deals with the colon as a possible target for the action of prokinetics.
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PMID:Recent advances in the pharmacology of gastrointestinal prokinetics. 893 12

Functional gut disorders include several clinical entities defined on the basis of symptom patterns (e.g., functional dyspepsia, irritable bowel syndrome, functional abdominal pain, functional abdominal bloating), for which there is no established pathophysiological mechanism. Because there is no well-defined pathophysiological target, treatment should be aimed at symptom improvement. Prokinetics and antispasmodics have been widely used in the treatment of functional gut disorders on the assumption that disordered motility is the underlying cause of symptoms, and symptom improvement is indeed achievable with these compounds in some, but not all, patients with features of hypo- or hypermotility, respectively. In the first part of this review, we cover the basic pharmacology and discuss the rationale for the clinical use of prokinetics and antispasmodics. On the other hand, in the past few years, the explosive growth in the research focusing on visceral sensitivity and visceral reflexes has suggested that at least some patients with functional gut disorders have altered visceral perception. Thus, the second part of the review covers these developments and focuses on studies addressing the issue of drugs modulating visceral sensitivity.
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PMID:Functional gut disorders: from motility to sensitivity disorders. A review of current and investigational drugs for their management. 980 54


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