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PubMed2005

Measurement of gastrointestinal transit.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

Breath Tests↗

PubMed2005

Effects of dexfenfluramine on serotonin levels of mice ileum, contractility, glutathione and malondialdehyde level.

UNLABELLED: Dexfenfluramine is one of the anorectic drugs that suppresses food intake which acts via inhibition of reuptake of serotonin into brain terminal. Gastrointestinal tract is the main source of peripheral serotonin which is involved in the regulation of gastrointestinal motility. During the use of anorectic drugs, the antioxidant defence is affected especially by reactive oxygen species. The purpose of this study to search: The effect of dexfenfluramine on serotonin levels of ileum and the effect of dexfenfluramine on ileal contractility and oxidative stress. MATERIALS AND METHODS: Twenty-two adult male Swiss-albino mice were divided two groups (1) Control, (2) Dexfenfluramine treated (i.p. twice a day 0.2 mg kg(-1) in 0.2 ml saline solution for 7 days). Animal body weights were recorded at the beginning and at the end of the experimental period. Ileum tissues contractile responses to different concentrations of KCl and acethycholine were recorded on polygraph. In the meantime ileal tissue malondialdehyde, a product of lipid peroxidation, and glutathione, endogenous antioxidant levels were assessed by spectrophotometric methods. Ileal tissue serotonin level determined by immunohistochemical method. Body weights decrease and ileal contractile response of acethycholine increased significantly by dexfenfluramine treatment. Meanwhile, ileum glutathione levels decreased and malondialdehyde levels increased in dexfenfluramine treated group. Immunohistochemical detection showed that ileal serotonin levels increased by dexfenfluramine treatments. As a conclusion, there is a relationship between increased ileal contractility and oxidant status in dexfenfluramine treated animals. These effects can be related by increased serotonin levels which is induced by dexfenfluramine in ileum.

Animals↗

PubMed2004

Delayed Gastric Emptying in Functional Dyspepsia.

Functional dyspepsia is a complex syndrome with a poorly defined pathophysiology, resulting in uncertainties in its therapeutic approach. Abnormalities in gastrointestinal motility and sensitivity alone or combined seem to play a role in a substantial subgroup of patients. Drugs capable of prokinetic effects, such as antidopaminergics (eg, metoclopramide, domperidone, levosulpiride) and serotonin 5-HT4 receptor agonists (eg, tegaserod) can be potentially used in the treatment of dyspeptic patients. Furthermore, 5-HT4 receptor agonists do not appear to increase the gastric fundus tone which may also contribute to improved symptoms in subsets of patients. Alosetron, a 5-HT3 receptor antagonist, has been investigated mainly in irritable bowel syndrome, and the few studies performed in functional dyspepsia have provided conflicting results. Erythromycin and related derivatives, the motilides, represent another class of prokinetic compounds able to accelerate gastric emptying and potentially indicated in functional dyspepsia. The stimulatory effect on fundic tone and the occurrence of tachyphilaxis hamper the efficacy of these drugs in the long-term treatment. kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but there are few available results and most are inconclusive. Results are also needed to prove efficacy of antidepressants (tricyclic agents and 5-HT reuptake inhibitors). Future clinical trials should be performed so that the formal structure required by good clinical practice can be adapted to detect significant effects in subgroups of patients with functional dyspepsia. Therapy should be ideally targeted to the different pathophysiologic abnormalities of these subgroups. The identification of the mechanisms leading to symptom generation should facilitate the development of newer and more effective therapeutic strategies in functional dyspepsia.

Journal Article↗

PubMed1992

Selecting optimum antihypertensive therapy: indications for choosing a calcium channel blocker.

In choosing the optimum antihypertensive agent for an individual patient, various factors should be considered. Demographic characteristics (e.g., age, gender, race) and the circadian pattern of blood pressure elevation may influence the response to therapy. Concomitant therapy for coexisting medical disorders must be evaluated for possible drug interactions. Calcium channel blockers, which can be used in any age group, may be particularly useful in hypertensive patients with certain concurrent conditions (e.g., coronary artery disease, migraine, or gastrointestinal motility disorders). Life-style, including occupation and leisure-time activities, may contraindicate the use of certain drugs in a particular patient. It also may be necessary to consider the economic status of the patient, particularly in the elderly, who often have limited disposable income. Since to a great extent successful therapeutic management of hypertension depends on patient compliance, reduced frequency of dosing (i.e., once or twice daily) is desirable. The clustering of morbid events in the hours immediately following awakening highlights the need for therapy that provides 24-hour control, thereby ensuring adequate pharmacodynamic effects during that crucial period. The challenge is to select the most appropriate first-line agent (diuretic, beta blocker, calcium channel blocker, or angiotensin-converting enzyme inhibitor) for a particular patient.

Age Factors↗

PubMed1980

Subconjunctival corticosteroid therapy complicated by hyperinfective strongyloidiasis.

A 57-year-old man was treated for a corneal ulcer with a penetrating keratoplasty, followed by six weeks of a regimen of 4 to 8 mg of dexamethasone injected subconjunctivally daily. Before therapy, he was clinically well and 10% eosinophils were noted on his differential white blood cell count. He developed a gastric peptic ulcer with hemorrhage and severe strongyloidiasis of the stomach and duodenum that worsened as the ulcer responded to medical therapy. The strongyloidiasis resulted in physiologic gastric outlet obstruction by decreasing gastrointestinal motility. There was evidence of hyperinvasive and disseminated strongyloidiasis, complicated by meningitis and Serratia marcescens bacteremia. He survived and received thiabendazole treatment for strongyloidiasis, which was successful. Subconjunctival corticosteroids caused a systemic effect that changed asymptomatic Strongyloides infection into hyperinvasive strongyloidiasis.

Conjunctiva↗

PubMed1994

Microinfusion of corticotropin releasing factor into the locus coeruleus/subcoeruleus nuclei stimulates colonic motor function in rats.

Convergent evidence indicates that brain corticotropin-releasing factor (CRF) participates in stress-related alterations of gastric and colonic motor function. CRF in the locus coeruleus has been shown to induce anxiogenic response. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric and colonic transit was investigated in conscious, chronically cannulated rats. CRF (0.2 nmol) microinjected into the LC/SC did not influence gastric emptying of a non-caloric semi-liquid meal while stimulating colonic transit by 57% as assessed by the geometric center in fasted rats. Under the same conditions, i.c.v. injection of CRF (0.2 nmol) delayed gastric emptying by 31% and increased colonic transit by 103%. When colonic transit was evaluated as the time of appearance in the feces of a marker placed in the proximal colon, CRF (0.2 nmol) injected into the LC/SC or i.c.v. stimulated colonic transit by 77% and 48% respectively and fecal output/6h by 3.8 and 2.8 fold respectively. Microinjection of CRF into the medial and lateral parabrachial nucleus, postero-dorsal tegmental nucleus, dorsomedial tegmental area and the ventral part of the nucleus subcoeruleus did not influence colonic transit. These data indicate that CRF acts in the LC/SC to induce a long lasting stimulation of colonic transit and bowel discharge without influencing gastric emptying. These findings suggest a possible role of the LC/SC in the regulation of colonic motor function and of endogenous CRF at these sites in the stress-related activation of colonic motor function.

Animals↗

PubMed1982

Effect of sauvagine on gastric emptying in conscious rats.

Sauvagine, a linear peptide with forty amino acid residues isolated from the skin of Phyllomedusa sauvagei, was injected s.c. and i.c.v. in conscious rats to determine its effect on gastric emptying (G.E.). Both i.c.v. and s.c. administration of the peptide produced a significant decrease in G.E. time. This effect was dose-related and lasted for 4 h following the injection. The potency of the peptide and its presence in the central nervous system suggest a physiological role in the mediation of gastrointestinal motility.

Amphibian Proteins↗

PubMed1984

Neurotensin receptors on the ileum of the guinea-pig: evidence for the coexistence of inhibitory and excitatory receptors.

Neurotensin caused a complex muscular response of the longitudinal muscle-myenteric plexus preparation of guinea-pig ileum: picomoles of neurotensin produced inhibition while larger concentrations caused an inhibitory effect followed by a delayed dose-dependent contraction. The inhibitory phase of the neurotensin-induced muscular activity was not modified by tetrodotoxin but was potently antagonized in a non-competitive manner by apamin, a bee venom toxin. The contractile component was blocked by tetrodotoxin but not by apamin. These toxins were used to dissect the neurotensin muscular response into an inhibitory phase and an excitatory component. It was possible to further characterize the two neurotensin muscular components by their kinetics of desensitization. The inhibitory neurotensin response showed a fast rate of desensitization and presented a relatively low spare receptor capacity. In contrast, desensitization to the excitatory action of neurotensin was much slower, the excitatory receptors apparently having a larger spare receptor capacity. Desensitization to the action of neurotensin was selective for the neuropeptide not altering the contractile activity of substance P, angiotensin II, bradykinin, histamine or acetylcholine. These results strongly suggest the presence of two subsets of neurotensin receptors in the ileum: the inhibitory set probably localized at the postsynaptic effector level and excitatory neurotensin receptors probably of neuronal origin whose function is probably to modulate the release of neurotransmitters. The physiological implications of these two subtypes of neurotensin receptors in the control of gastrointestinal motility are discussed.

Animals↗

PubMed1992

Further investigations on the antipropulsive effect of centrally administered histamine and its relation with morphine.

The effect of intracerebroventricularly (i.c.v.) administered histamine (100 micrograms/rat) on intestinal myoelectrical activity was investigated in the jejunum of fasted rats. Histamine caused the disappearance of phase III and a partial reduction of phase II of migrating myoelectric complexes. This effect was antagonized by i.c.v. pretreatment with mepyramine (10 micrograms/rat), an H1 receptor antagonist. Lesions of central noradrenergic neurons by i.c.v. injection of the neurotoxin 6-hydroxydopamine strongly reduced both the inhibition of intestinal propulsion and the migrating myoelectric complexes profile induced by i.c.v. histamine, whereas pretreatment with p-chlorophenylalanine, a selective depletor of serotonin stores, had no effect. It thus appears that aminergic pathways are involved in the visceral effects of central histamine. Mepyramine (200 micrograms/rat i.c.v.) partially reduced the slowing of intestinal transit induced by high doses of morphine. Pretreatment with compound 48/80 (10 micrograms/rat i.c.v.), a mast cell degranulator, but not with alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, reduced the antipropulsive action of i.c.v. morphine to the same extent as mepyramine, suggesting that histamine released from cerebral mast cells by high doses of morphine could contribute to the intestinal inhibition by morphine.

Animals↗

PubMed1987

Localization of specific binding sites for bombesin in the canine gastrointestinal tract.

The goal of these studies was to determine the tissue and cell types possessing specific binding sites for bombesin/gastrin-releasing peptide in the canine gastrointestinal tract. Monoiodinated, biologically active (Tyr-4)-bombesin 14 (100 pM) was applied to sections of canine gut and localized using quantitative autoradiography. The highest density of bombesin/gastrin-releasing peptide specific binding sites occurred over endocrine cells in the antral mucosa. Specific binding sites were also found on the circular muscle layer of the gastric fundus, gastric antrum, and ileum, on longitudinal muscle of the gastric fundus and antrum, and on neuronal elements in the myenteric plexus in the gastric fundus, antrum, and small intestine. No evidence for specific binding of 125I-(Tyr-4)-bombesin 14 was found in sections of canine esophagus, gastric cardia, gallbladder, pancreas, or colon. These results suggest sites of direct action of bombesin and endogenous gastrin-releasing peptide for gastrin release and gastrointestinal motility.

Animals↗

PubMed1990

Gastric protective activity of mixtures of saturated polar and neutral lipids in rats.

It has been shown that intragastric treatment of rats with a suspension of dipalmitoylphosphatidylcholine and tripalmitin at a 1:4 ratio (5 mg lipid/mL per rat) provided rats with highly efficaceous and consistent protection against a variety of ulcerogenic agents and conditions. The gastric protective activity of this mixture was of long duration (t 1/2 approximately 9 hours. In an attempt to understand the mechanism of protection, it was determined that the ulcerogen-induced reduction in gastric surface hydrophobicity was reversed in rats pretreated with the mixture. However, the lipid mixture did not affect the gastric emptying rate and maintained its cytoprotective activity in indomethacin-treated rats. These results indicate that the mixture's protective effect was not mediated by alterations in either gastrointestinal motility or the gastric accumulation of lipids or "cytoprotective" metabolites (prostaglandins). The mixture also appreciably reduced gastric lesion score in response to acid if one or both the lipids was substituted for a metabolically inert ether analogue, suggesting that lipid metabolism makes a negligible contribution to the protective response. Electron microscopic observation indicated that the predominent structure in the mixture is a microemulsion in which a dipalmitoylphosphatidylcholine monolayer encapsulates a tripalmitin core. Last, the improved gastric protective activity of the mixture in comparison to dipalmitoylphosphatidylcholine liposomes is discussed regarding marked differences in the physical structure of the two suspensions and the rate at which lipids in these states adsorb to a surface to enhance its hydrophobic properties.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1993

Fluid loading of the human colon: effects on segmental transit and stool composition.

BACKGROUND: Because segmental storage by the colon is relevant to diarrheal states, we quantified colonic transit in 13 healthy volunteers. METHODS: We infused radiolabelled liquids and solids into the cecum. Gamma camera images were obtained for 48 hours and counts measured in ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colons. Bowel movements were scored for consistency and stool outputs of isotopes were quantified. RESULTS: No volunteers developed diarrhea. Times for isotopes to transverse AC and TC were shorter with rapid infusions (P < 0.001). Counts remaining in AC and TC were also correlated with infusion volumes for 9 hours but not thereafter. Solids were initially delayed in AC but solids and liquids were stored equally in TC. Transit through DC was rapid, but RS stored contents for many hours. First appearance of counts in stools and total counts excreted after 48 hours were not dependent on the infusion rate. Fecal consistency and water content correlated significantly with colonic transit times. CONCLUSIONS: Fluids moved ahead of solids in the AC, but liquids and solids were stored equally in the TC. The DC acted mainly as a conduit during fluid overload but the RS stored both isotopes extensively. Stool consistency was a valid reflection of total colonic transit.

Adolescent↗

PubMed1995

Hyperglycemia alters perception of rectal distention and blunts the rectoanal inhibitory reflex in healthy volunteers.

BACKGROUND/AIMS: Acute hyperglycemia has been shown to alter gastrointestinal motility. The effects of hyperglycemia on rectal afferent neural and anal sphincter function were studied. METHODS: Perception of rectal balloon distention, pressure-volume relationships, volumes necessary to induce reflex internal anal sphincter relaxation, resting anal sphincter pressure, and maximal anal sphincter squeeze pressure were measured under basal, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions in 9 healthy volunteers. RESULTS: Hyperglycemic clamping (258 +/- 14 mg/dL) significantly blunted threshold perception and the urge to defecate in response to rectal distention without altering perception of maximally tolerated distention. In contrast, euglycemic, hyperinsulinemic clamping had no effect on perception of rectal distention. Rectal pressure-volume relationships after hyperglycemic clamping were unchanged compared with basal conditions. Hyperglycemic clamping caused a significant increase in the distention necessary to induce the rectoanal inhibitory reflex. This effect was not observed under euglycemic, hyperinsulinemic clamp conditions. Hyperglycemia did not significantly affect resting internal anal sphincter pressure or maximal external anal sphincter squeeze pressure. CONCLUSIONS: Acute hyperglycemia but not secondary hyperinsulinemia reduces sensation of rectal distention and blunts the onset of the rectoanal inhibitory reflex, suggesting effects both on visceral afferents projecting to the cortex and intrinsic afferents mediating local reflex activity.

Adult↗

PubMed1991

Capillary zone electrophoresis studies of motilin peptides. Effects of charge, hydrophobicity, secondary structure and length.

Motilin is a gut hormone, which is involved in gastrointestinal motility. Capillary electrophoresis studies were made on 24 peptides that are N-terminal, C-terminal or internal fragments of motilin. The isoelectric point, total charge and hydrophobicity were calculated for all of the peptides. The effects of buffers and pH on migration time and resolution were studied. These included citrate buffer, pH 2.5; phosphate buffer, pH 7.0 and borate buffer, pH 10.0. A capillary zone electrophoresis method was developed to resolve 14 of the motilin peptides. Secondary structure predictions were made using the Chou-Fasman method. Circular dichroism spectra were collected to confirm presence of alpha-helix in several fragments. Effects of charge, hydrophobicity, secondary structure and length of the motilin fragments on migration time were studied.

Amino Acid Sequence↗

PubMed1994

Effect of rectal distention and feeding on cecal tone in pigs.

The effects of eating and rectal distention on cecal tone were evaluated. Cecal tone was measured using a computer-controlled barostat in four female 30 to 40 kg Yucatan Micropigs fitted with cecal fistulas. Each pig underwent two separate trials of pre and postprandial measurements of cecal tone, either with or without continuous rectal distention with a 30 ml water-filled balloon. Cecal tone was measured 10 min prior to, during, and 10 min following a high-fat (60%) liquid meal (473 ml). Cecal tone significantly increased (intrabag volume decreased) after feeding (119.6 +/- 9.1 ml vs. 81.2 +/- 7.9 ml; p = 0.008). Rectal distention tended to reduce the postprandial change in cecal tone (142.8 +/- 11.5 vs. 130.9 +/- 12.6 ml; p = 0.196). There was also a strong tendency for cecal volumes to be higher (decreased tone) with rectal distention preprandially (142.8 +/- 11.5 ml vs. 119.6 +/- 9.1 ml; p = 0.024). Nutrient ingestion significantly increased cecal tone and rectal distention abolished this effect. These findings may indicate a regulatory pathway that allows additional storage of fecal material in the event that the output of the system is disturbed.

Animals↗

PubMed1985

Computer-aided analysis of gastrointestinal myoelectric activity.

This method of analysing gastrointestinal motility involves data collection for 12 h periods and calculations from electromyographic signals at 15 s intervals; results are printed for successive 20 min epochs. In addition, phases of regular spike activity are recognized during the interdigestive periods. The system has been used in a series of comparative measurements of duodenal activity before and after feeding, and in studies involving drug-induced regular spike activity.

Action Potentials↗

PubMed1990

Untreated anorexia nervosa. A case study of the medical consequences.

This case demonstrates the devastating physical sequelae of 30 years of untreated anorexia nervosa. A full array of these consequences occur in this one patient and include the following: malnutrition and hypoproteinemia, electrolyte disturbances, cortical atrophy with hydrocephalus ex vacuo, tricuspid and mitral valvular dysfunction, anemia, impaired lower gastrointestinal motility, delayed gastric emptying, disturbances in the hypothalamic pituitary target organ axes, severe osteoporosis, marked edema, and extreme muscle wasting. Other possible physical sequelae of her anorexia nervosa are discussed. Psychiatrists, as well as other physicians, should be vigilant in diagnosing this illness and treating it as early as possible. This particular patient was in the medical system for numerous admissions and workups over three decades before the correct diagnosis of anorexia nervosa was made.

Aged↗

PubMed1992

Effect of chemical sympathectomy on scintigraphic gastric and small bowel transit in the rat.

Our aims were to measure gastric and small bowel transit of radiolabeled chow or liquids in rats and to assess the effect of pharmacologically induced chronic sympathectomy of at least 5 weeks duration. Three series of experiments were performed. In series I, four rats in each group underwent i.p. chloral hydrate anesthesia, tracheostomy with intubation and mechanical ventilation: they received by gavage 1.0 g rat chow dissolved in 1.5 ml saline labeled with 1.0 mCi 99mTc-DTPA In series II, four rats in each group were anesthetized with only i.p. chloral hydrate and received 1.5 ml labeled saline. Rats were placed on a gamma camera for dynamic acquisition of 1-min images for 7 h in series I, and 4 h in series II. Activity was quantitated in stomach and cecum; gastric emptying was analyzed by the power exponential model. In series III, four rats in each group were studied for 1 h on gamma camera and sacrificed after 5 h. At the end of each study, the stomach, small bowel, cecum and colon were removed and radioactivity counted in each organ in a dose calibrator. Quantitation of radioactivity by gamma camera was highly accurate: labeled chow in the stomach at 7 h was identical by external camera and counting of the excised organ (linear regression slope = 1.01, r = 0.97, P less than 0.0001). Similar precision was observed with labeled liquids (slope = 0.93, r = 0.93, P = 0.001). Chow emptied slower than liquid in both groups (P = 0.048). Ileocecal movement of isotope occurred by bolus transfers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗