Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alteration in visceral sensation locally at the site of presumed symptom origin in the gastrointestinal tract has been proposed as an important etiopathological mechanism in the so-called functional bowel disorders. Patients presenting with one functional gastrointestinal syndrome, however, frequently have additional symptoms referable to other parts of the gut, suggesting that enhanced visceral nociception may be a panintestinal phenomenon. We measured the sensory thresholds for initial perception (IP), desire to defecate (DD), and urgency (U) in response to rectal balloon distension, and the thresholds for initial perception and for discomfort in response to esophageal balloon distension in 12 patients with irritable bowel syndrome (IBS) and 10 patients with functional dyspepsia (FD), in comparison with healthy controls. As expected, IBS patients exhibited lower rectal sensory thresholds than controls (P < 0.0001), but in addition had significantly lower sensory thresholds for both perception and discomfort evoked by balloon distension of the esophagus (mean +/- SEM: 8.8 +/- 1.3 ml vs 12.1 +/- 1.5 ml (P < 0.05) and 12.2 +/- 1.4 ml vs 16.4 +/- 1.4 ml (P < 0.02) respectively. Patients with FD showed similarly enhanced esophageal sensitivity, with thresholds for perception and discomfort of 8.1 +/- 0.9 ml (P < 0.02), and 10.1 +/- 1.0 ml (p < 0.001), respectively, but were also found to have sensory thresholds for rectal distension similar to those observed in the IBS group, significantly lower than in controls: IP 45.0 +/- 17.6 vs 59.3 +/- 1.5 ml (P < 0.001), DD 98.0 +/- 17.9 vs 298.7 +/- 9.0 ml (P < 0.0001), U 177.2 +/- 25.4 vs 415.1 +/- 12.6 ml (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. 764 57

Structure-activity studies demonstrate that galanin fragments 1-15 and 2-29 are fully active, whereas fragment 3-29 has been reported to be inactive, in a number of different in vivo models. M15, a chimeric peptide comprising galanin 1-13 and substance P5-11, has recently been found to be a potent galanin antagonist. Direct effects of galanin at the level of the pituitary have been defined, yet, paradoxically, a number of studies have been unable to demonstrate galanin binding to an anterior pituitary receptor. Porcine galanin stimulated prolactin release from dispersed rat anterior pituitary cells up to 180% +/- 12% (mean +/- SEM) of control secretion. The addition of a specific galanin antiserum caused a profound inhibition of basal prolactin release, maximal inhibition being 12% +/- 0.5% of control secretion. Addition of M15 produced no effect on basal or galanin-stimulated prolactin release. Galanin fragment 3-29 was fully active when compared to galanin 1-29. Fragments 5-29 and 8-29 stimulated prolactin release to a lesser extent and galanin 1-15, 10-29, and 20-29 had no significant prolactin-releasing activity. Using [mono(125I)iodo-Tyr26]galanin or porcine 125I-labeled Bolton-Hunter [mono(125I)iodo-Lys25]galanin, no anterior pituitary membrane binding was observed. In contrast, 125I-labeled Bolton-Hunter N-terminally labeled galanin allowed characterization of a single high-affinity anterior pituitary galanin receptor with a Kd of 4.4 +/- 0.34 nM and a Bmax of 79 +/- 8.3 fmol/mg of protein. The IC50 for porcine galanin was 0.51 +/- 0.04 nM but for M15 was in excess of 10 microM. Galanin 3-29 fully displaced the label with an IC50 of 0.96 +/- 0.7 nM. The IC50 for galanin 5-29 was 200 nM, whereas 8-29 and 1-15 were > 1 microM. Galanin 10-29 and 20-29 failed to displace the label. These data suggest the presence of a high-affinity pituitary galanin receptor, designated GAL-R2, in which region 3-10 and amino acid 25 are crucial for membrane binding and biological activity, in contrast to the known gut/brain galanin receptor (designated GAL-R1). A number of tissues known to bind or respond to galanin were screened. GAL-R2 would appear to be expressed only in the anterior pituitary and hypothalamus.
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PMID:Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor. 768 28

Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with ensuing mucosal repair. This study investigated possible roles for gut vasoactive neuropeptides and trophic peptides in these phenomena. Groups of rats were monitored during superior mesenteric artery occlusion for five or 20 minutes, with or without subsequent reperfusion for five minutes. Peptide concentrations (fmol/ml) in arterial blood, were measured using specific radioimmunoassays. Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide release. Reperfusion, after five minutes of ischaemia, resulted in arterial hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM)) (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion resulted in greater hypotension (p < 0.05) and release of both vasoactive intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p < 0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin were not released. Bombesin, a stimulatory neuropeptide, was released after 20 minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27) (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene related peptide, unopposed by vasoconstrictors, may promote post-ischaemic intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse mucosal injury and is consistent with the putative trophic role of this peptide.
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PMID:Release of vasodilator, but not vasoconstrictor, neuropeptides and of enteroglucagon by intestinal ischaemia/reperfusion in the rat. 782 5

The digestibility of ispaghula, a mucilage from Plantago ovata composed mainly of arabinoxylans, and its faecal bulking effect were studied in seven healthy volunteers who ingested a low fibre controlled diet plus either placebo or 18 g/day of ispaghula for two 15 day periods. Whole gut transit time and gas excretion in breath and flatus were not different during the periods of ispaghula and placebo ingestion. Faecal wet and dry weights rose significantly, however, during ispaghula ingestion. Faecal short chain fatty acid concentrations and the molar proportions of propionic and acetic acids also increased. Most of the ispaghula had reached the caecum four hours after ingestion in an intact highly polymerised form. During ispaghula ingestion, the increase in the faecal output of neutral sugars was accounted for by the faecal excretion of arabinose and xylose in an intact highly polymerised form; the apparent digestibilities of these sugars were 24 (11) and 53% (6) respectively (mean (SEM)). In conclusion, ispaghula is more resistant to fermentation than previously reported in humans, and its bulking effect largely results from intact material.
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PMID:Digestibility and bulking effect of ispaghula husks in healthy humans. 782 13

Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol. 788 76

It is unclear whether menaquinones produced by the intestinal microflora play any role in human nutrition. Reports of coagulopathy due to vitamin K deficiency occurring in patients receiving broad spectrum antibiotics indirectly suggest that vitamin K2 produced by the gut microflora may be utilized by the host. We analyzed the vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) content in a convenience sample of 22 human post-mortem liver samples, including 9 individuals who had been receiving broad spectrum antimicrobials prior to death and 13 individuals who had been victims of sudden, unexpected deaths. There were no significant differences in the mean (+/- SEM) phylloquinone content between the 2 groups [21.9 (+/- 15.5) vs. 16.0 (+/- 9.3) pmol/g wet weight (excluding those who had received supplemental vitamin K1)] but there was a significant difference (p < 0.05) in the total menaquinone (MK) content, 70.0 (+/- 23.3) vs. 423.1 (+/- 141) pmol/g between the 2 groups. These findings suggest an association between receipt of broad spectrum antibiotics and a reduction in hepatic menaquinone concentration, lending support to the hypothesis that a reduction in the gut microflora responsible for their production leads to reduced hepatic stores of this form of the vitamin.
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PMID:Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. 789 17

Interleukin-1 (IL-1) may be involved in gut permeability to macromolecules and gut glutamine metabolism during endotoxemia. We developed a sensitive radioimmunoassay specific for mouse IL-1 alpha (detection limit of 100 pg/ml, or 5 pM) and measured intestinal levels of IL-1 alpha in response to endotoxin. CD-1 mice (N = 190) were randomized to intraperitoneal (ip) or intravenous (i.v.) lipopolysaccharide (LPS) infusion (15 micrograms/g or 1.5 micrograms/g Escherichia coli 0111:B4 LPS) or saline. Mice were sacrificed at Time 0, 30 min, 1 hr, 2.5 hr, 4 hr, 6 hr, 12 hr, and 24 hr (3 mice/group/time point). Small bowel (SB) and large bowel (LB) were harvested and compared to liver. Duodenum, upper jejunum, midjejunum, terminal ileum, cecum, ascending colon, and sigmoid were analyzed in separate experiments. Tissues were frozen, weighed, and homogenized, the homogenates were centrifuged, and the supernates were assayed for immunoreactive IL-1 alpha. IL-1 alpha was expressed as pg/g wt +/- SEM (lowest detectable amount = 1000 pg/g wet tissue (WT)). SB but not LB from normal controls had constitutively elevated levels of IL-1 alpha (6177 +/- 1640 pg/g WT). LPS ip or i.v. produced lethargy, diarrhea, and a dramatic elevation of IL-1 alpha levels in both SB and LB. In SB, IL-1 alpha was elevated compared to baseline at 1 hr (19201 +/- 626 pg/g WT) and reached a fivefold maximal increase at 2.5 hr (31775 +/- 503 pg/g WT) following 15 micrograms/g ip.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal production of interleukin-1 alpha during endotoxemia in the mouse. 841 68

Previous studies have suggested that the cyclic entry of bile into the duodenum during fasting regulates interdigestive patterns of motility by releasing the putative regulatory hormone motilin. Our aim was to determine if cyclic secretion of bile into the duodenum regulates interdigestive myoelectric activity and plasma motilin concentrations. Six dogs were prepared with gastric and intestinal serosal electrodes. Myoelectric activity was measured during fasting and after a meal before and after reoperative translocation of the entrance of the bile duct to the mid-jejunum. The characteristics of the migrating myoelectric complex (MMC) and conversion to a postprandial pattern were similar before and after bile duct translocation. The period (112 +/- 5 vs 109 +/- 10 min; mean +/- SEM), migration velocity of phase III through the duodenum (8.9 +/- 1.2 vs 6.8 +/- 0.5 cm/min), and duration of individual phases of the MMC in the stomach, duodenum, and jejunum were not altered significantly (each P > 0.05) by chronic diversion of bile from the duodenum. Plasma motilin concentrations were similar before and after bile duct translocation (P > 0.05), continued to cycle temporally with the MMC, and peak concentrations occurred during phase III and were greater than during phases I and II (P < 0.01). We conclude that the presence of bile in the lumen of the duodenum does not regulate interdigestive myoelectric patterns of the canine upper gut or the cyclic release of motilin.
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PMID:Chronic bile diversion does not alter canine interdigestive myoelectric activity. 850

The tonometric method of detecting decreased gut intramucosal pH (pHi) is based on the fact that carbon dioxide can diffuse through the wall of the silastic balloon of the tonometer. By using deoxified saline and measuring PO2 as well as PCO2 this study aimed to follow changes in mucosal PO2 and relate them to changes in pHi in peritonitis versus haemorrhage. Twenty five pigs were used. Five were controls, in 10 peritonitis was induced by the instillation of faeces in the abdominal cavity, and 10 were bled, half of them stepwise during three hours, and half of them rapidly down to a mean (SEM) arterial pressure of 30 (10) mm Hg. The drop in pHi correlated well with decreasing intraluminal PO2 (r = 0.63 (0.13)) in haemorrhage. In peritonitis this drop occurred within a very limited change in intraluminal PO2 (r = 0.06 (0.17)). Thus oxygen seemed to be present in the mucosa at the same time as there were signs of anaerobic metabolism as evidenced by a low intramucosal pH. Impaired oxygen extraction or utilisation, or both, is proposed as an explanation to this seemingly paradoxical situation.
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PMID:Gut intramucosal pH and intraluminal PO2 in a porcine model of peritonitis or haemorrhage. 853 49

Ileal and fecal gut endogenous nitrogen and amino acid excretions in adult domestic cats were determined. Ileal digesta were collected (10 cm of terminal ileum) from the cats fed either a protein-free diet or an enzymatically hydrolyzed casein-based diet (free amino acids and peptides < 10,000 Da) for 1 wk. Chromic oxide was included in each diet as an indigestible marker. The relative contribution of the hindgut to total endogenous gut excretion was investigated in a separate study by feeding cats a protein-free diet with or without added antibiotics for 10 d. Endogenous ileal nitrogen and amino acid nitrogen excretions of (mean +/- SEM 2.4 +/- 0.27 and 1.9 +/- 0.13 mg/g food dry matter intake, respectively, were found for the cats fed the protein-free diet, whereas higher excretions of 3.6 +/- 0.73 (P = 0.12) and 3.6 +/- 0.76 (P = 0.03) mg/g food dry matter intake were obtained in cats fed the enzymatically hydrolyzed casein. Significantly (P < 0.05) higher endogenous ileal amino acid excretions, for the enzymatically hydrolyzed casein-fed cats compared with those fed the protein-free diet, were found for methionine, aspartic acid, serine, glutamic acid, proline, valine and isoleucine, with the differences in excretions of glycine, alanine, leucine and histidine being significant at the 6% level. Most of the endogenous fecal amino acid excretions were unaffected by the inclusion of the antibiotics in the protein-free diet, although bacterial numbers were significantly lower (69%). Antibiotics addition led to significantly higher fecal endogenous excretions of nitrogen, taurine, threonine, serine and histidine but significantly lower excretions of methionine and lysine. Cats, like other simple-stomached mammals, excrete higher amounts of endogenous amino acids at the terminal ileum when the diet contains peptides.
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PMID:Gut endogenous nitrogen and amino acid excretions in adult domestic cats fed a protein-free diet or an enzymatically hydrolyzed casein-based diet. 861 99


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