Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischaemia of the small intestine leads to the destruction of the intestinal mucosa. The capacity of the epithelium to regenerate is proportional to the duration of revascularization. The aim of this work was to analyze the kinetic aspects of intestinal epithelial regeneration after destruction due to prolonged ischaemia. This study was conducted in 44 animals (swine) after development of an ischaemia-revascularization protocol of a jejunal loop and bipolar secondary cutaneous exteriorization. After a first series with ischaemia times of 1, 2, 3 and 4 hours, the 4 hour period of ischaemia was chosen for further analysis of the regeneration kinetics over a period of 21 days since it leads to regular and total destruction of the epithelium compatible with regeneration. This analysis included (1) a histological examination (semi-thin slices), (2) immunofluorescent detection of intestinal brush border proteins on frozen slices (villin, saccharase-isomaltase, aminopeptidase N, dipeptidylpeptidase-IV) and mucines, (3) measurement of specific intestinal hydrolase activities (saccharase, aminopeptidase N, dipeptidylpeptidase-IV and alkaline phosphatase) in enriched brush border fractions, and (4) an analysis of variations in intestinal flora. After the 4 hour ischaemia, total destruction of the epithelium with disappearance of the villin and intestinal hydrolases and disorganization of the mucosa invaded by mucosal lacks was observed. Epithelial regeneration was rapid and two days later the histological aspect of the mucosa showed apical expression (still discontinuous), villin and intestinal hydrolase activity. Luminal apical expression of the markers became continuous on day 4, demonstrating the total recovery of the intestinal barrier as confirmed by stable microbial flora. Mucine expression also returned to normal. This regeneration was however incomplete since the mucosa was seen to be flat, without villosities. Immunofluorescence showed the weak intensity of brush border activity and the very low specific activity of hydrolase. Values were below normal and did not start to rise again until day 21. If serum levels and associated brush border markers could be measured and were significant, they could be specific markers of regeneration in double stomy ischaemic-revascularized intestine and thus eliminate the need for early second look laparotomy.
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PMID:[Effects of ischemia and revascularization on the epithelium of the small intestine: study on swine]. 798 9

Jejunal expression of three brush-border membrane (BBM) enzymes, intestinal alkaline phosphatase (IAP), lactose-phlorizin hydrolase (LPH), and sucrase-isomaltase (SI), and a cytosolic protein, ferritin (Ft), was investigated after transient segmental ischemia-reperfusion (I/R). I/R reduced mucosal IAP, LPH, and SI mRNAs to 36%, 11%, and 38% of normal jejunal levels after 3 h of reperfusion and to 22%, 8%, and 51% of normal jejunal levels after 6 h of reperfusion, respectively. Intriguingly, in the internal control jejunum IAP and LPH mRNAs also decreased significantly. LPH and SI mRNA rapidly recovered to levels significantly higher than those of normal jejunum at 12 h, whereas IAP mRNA levels did not recover until 48 h. Enzyme activity paralleled changes in mRNA levels in the ischemic reperfused jejunum. Electrophoretic mobility shift assays showed that I/R significantly increased SI footprinting 1 (SIF1) binding activity. The mobility of one of the DNA-protein complexes was further retarded in the presence of anti-Cdx-2 antibody, suggesting that either Cdx-2 or a related protein was interacting with the SIF1 sequences. Similar to BBM enzymes, cytosolic Ft mRNA and protein were significantly decreased at 3 and 6 h after I/R. By 12 h, Ft mRNA, but not Ft protein, had increased to higher than normal levels. We conclude that a rapid recovery of BBM mRNAs and enzymes occurs in regenerating mucosa after upper villus damage. The increase of SIF1 binding protein activity after I/R may enhance SI, and perhaps LPH, gene transcription. The expression of Ft is regulated at both pretranslational and translational levels.
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PMID:Expression of intestinal brush-border membrane hydrolases and ferritin after segmental ischemia-reperfusion in rats. 972 71