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Effects of intestinal muscular wrapping on remnant intestinal motility after massive small bowel resection in conscious canines.

We searched the effect of the muscular valve on the management of short bowel syndrome. The motility of the remnant intestine with a special muscular valve after 80% massive distal small bowel resection (MSBR) was evaluated in conscious dogs. The valve (muscular ring) was made by the autointestinal muscle layer holding vascular pedicle. Interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gauge force transducers 2-4 weeks after the surgery, and data of this group (Group I) were compared to the motility in dogs after MSBR without valve construction (Group II) and in controls (Control). Results; Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) in Group I occurred at longer intervals than in Control and almost similarly to those in Group II. MMCs arising from the duodenum were often interrupted before the jejunum above the valve and the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment including that from the duodenum to the proximal jejunum, and to the jejunum above the anastomosis. Transit time in MSBR group (I and II) from the duodenum to the terminal ileum was extremely shorter than in Control, but there were no differences between in Groups I and II. The duration of the postprandial period without duodenal MMCs in Group I was significantly prolonged than in Control, but was shorter than that in Group II. The muscular valve was frequently activated, and the jejunum covered with the valve was contracted frequently which synchronized with the valve activity. It seemed the valve worked as sphincter. However, intestinal obstruction was not occurred through the jejunum covered by the valve. In conclusion, changes in gut motility after MSBR with the valve construction compensate for the shortened intestine and maintain the bowel content earlier postoperatively in comparison with the MSBR alone, and also contribute to the adaptive increase in the remnant intestinal absorption.

Animals↗

Effects of restricted diet and intestinal flora on the life span of small intestine epithelial cells in mice.

Previous data have shown that the life span of small intestine epithelial cells in germ-free (GF) mice was 4.3 days, while that in conventional (CV) mice was 2.1 days, under ad libitum feeding. On the other hand, in the author's laboratory, it was also found that feeding conditions affected the cells' life span. That is, in CV mice the life span of the cells lengthened under restricted feeding (2.6 days), compared with under and libitum feeding (1.8 days). In the present experiment the life span of small intestine epithelial cells was investigated using radioautography, under controlled feeding (setting it equal to ad libitum feeding) and restricted feeding, in both CV and GF mice. Small intestine samples were taken from the middle part of duodenum, jejunum and ileum. Body weight changes, organ wet weights and intestine were also measured. In the lower part of the small intestine the effects of a restricted diet on epithelial cell life span prolongation appeared clearly in CV mice, but this effect was reduced in GF mice. This may be partly because the restricted group had slightly shorter villi in the case of GF mice.

Animals↗

[Intensive effect of traditional Chinese medicines activating blood to resolve stasis on medicines dredging intestines--influence on peristalsis of small intestine in guinea pigs].

OBJECTIVE: To observe the changes of peristalsis of small intestine in guinea pigs after administration of traditional Chinese medicines activating blood to resolve stasis (Compound Danshen Decoction, CDSD) or/and medicines dredging intestines (Dachengqi Decoction, DCQD), and to explore the synergetic or intensive effect of CDSD on DCQD. METHODS: By means of BL-420 Biological Experimental System, peristalsis of small intestine was recorded and analyzed following administration of DCQD, CDSD or Huoxue Chengqi Decoction (HXCQD, compound of CDSD and DCQD) respectively in different experimental periods. RESULTS: The amplitude and frequency of intestinal peristaltic wave obviously increased following administration of the three decoctions, but HXCQD appeared to be most dominantly. CONCLUSION: The effect of DCQD can be further enhanced by combining use of CDSD, suggesting that the traditional Chinese medicines activating blood to resolve stasis have an intensive effect on medicines dredging intestines.

Animals↗

Intact intestinal mRNAs and intestinal epithelial cell esterase, but not Cryptosporidium parvum, reach mesenteric lymph nodes of infected mice.

Dendritic cells from the mesenteric lymph nodes (MLN) contain dense esterase-positive inclusions that may originate in effete intestinal epithelial cells and reach MLN without degradation. The MLN esterases have the electrophoretic mobilities of both intestinal and mononuclear cells. Cryptosporidium parvum (CP)-infected mice have CP Ag-positive cells in MLN and also increased numbers of dense esterase-positive cells, but the CP Ag-positive cells do not stain for esterase. To characterize the handling of epithelial cell products by dendritic cells, we analyzed mRNAs in the MLN of control and CP-infected recombination-activating gene(-/-)DO11.10 mice by oligoarrays. mRNAs for 115 proteins were increased in MLN after CP infection, of which the principal increases in trypsin and chymotrypsin approximated to 250-fold. Colipase, reg-1, C-reactive protein-ductin, and amyloid were also up-regulated >10-fold and all returned to baseline by 28 days after infection. mRNAs for the same proteins were detected in intestinal epithelial cells of infected mice by oligoarrays and RT-PCR after infection. mRNA for CP beta-tubulin was detectable in intestinal epithelial cells between 5 and 18 days after infection but was not detected in the MLN throughout the observation period. It appears that host response to CP infection includes expression of mRNA for some pancreatic enzymes by intestinal epithelial cells and their subsequent transport to the MLN. The esterase and trypsin, and mRNAs for chymotrypsin, colipase, and others that may derive from uninfected epithelial cells, appear to be transported to the MLN intact, while mRNA for CP beta-tubulin that is derived from infected cells is degraded.

Animals↗

Cyclin D1 is not an essential target of beta-catenin signaling during intestinal tumorigenesis, but it may act as a modifier of disease severity in multiple intestinal neoplasia (Min) mice.

Deregulation of beta-catenin activity is an important step in the development of colorectal cancers. One consequence of this is transcriptional activation of cyclin D1, an oncogene known to be overexpressed in colorectal cancers. We tested the hypothesis that cyclin D1 gene activation is important for intestinal tumorigenesis. Multiple intestinal neoplasia mice (a model for human familial adenomatous polyposis) were crossed with cyclin D1 knockout (Ccnd1(-/-)) mice. Despite the absence of cyclin D1, intestinal tumors still developed. However, Ccnd1(-/-) multiple intestinal neoplasia mice developed significantly fewer tumors than Ccnd1(+/-) or Ccnd1(+/+) mice (P = 0.003). We conclude that cyclin D1 is not essential for intestinal tumorigenesis, but it may act as a modifier gene.

Animals↗

[Experimental study on the effects of intestinal trefoil factor on intestinal epithelial proliferation and its signal transduction mechanism].

OBJECTIVE: To explore the effects of intestinal trefoil factor (ITF) on intestinal epithelial proliferation and its possible signal transduction mechanism. METHODS: 1). The intestinal epithelial cytoplasmic membrane was isolated and harvested from Wistar rats, and it was treated with various doses of ITF in the concentration of 0.01, 0.10, 1.00 and 10.00 micro g/ml. The tyrosine protein kinase (TPK) activity from cytoplasmic membrane ITF receptor was determined by membrane-bound method. 2). The intestinal epithelial cells 6 (IEC-6) cultured in vitro were employed in the study. Some of the cells were used as normal control, while a group of cells were stimulated by 1 micro g/ml ITF, and others were treated by PD098059, SB202190 and SB202474, respectively. The last three agents were inhibitors of three members of mitogen-activated protein kinase family (MAPKs), i.e. extracellular signal regulated protein kinases (ERKs), protein kinase p38 (p38), and stress-activated protein kinase (SAPK). They were used before the addition of 1 micro g/ml of ITF. The changes in DNA synthetic rate and the MAPK activity of IEC-6 after being treated by above agents were assessed by (3)H-TdR incorporation method. RESULTS: ITF receptor possessed TPK activity. TPK activity of ITF receptor, MAPKs activity and DNA synthetic rate of IEC-6 were increased obviously under the stimulation of ITF (P < 0.01). The above ITF effects could be evidently blocked by PD098059 and partially attenuated by SB202474. But SB202190 showed no effect in this respect. CONCLUSION: ITF could promote intestinal epithelial proliferation and transmit extracellular signals mainly by means of ERKs signalling pathway.

Animals↗

[Mucus models for investigation of intestinal absorption mechanisms. 4. Comparison of mucus models with absorption models in vivo and in situ for prediction of intestinal drug absorption].

Intestinal absorption with an in vitro model using pig intestinal mucus was examined by means of in vivo and in situ experiments in the rat. With 10 compounds of different structure, in vitro, in situ, and in vivo models were tested. The in vitro model in the present form can only simulate the first step of intestinal absorption, namely diffusion through the mucus layer. Indeed, we found that one function of the intestinal mucus can be described being a molecular sieve with a molecular mass (MM) cut off within the range of about 600 to 700 [g/mol]. Absorption of substances with higher molecular mass remains at a low level. With the mucus model prediction of intestinal absorption of hydrophilic substances with MM < 600 to 700 [g/mol] will be possible, if the mass transport in the mucus layer is rate limiting. Independent of polarity, it is also valid for substances of MM > 600 to 700 [g/mol]. Estimation however, is not valid for lipophilic substances and MM < 600 to 700 [g/mol], when mass transport from the mucus to the adjacent compartments is rate limiting. Further optimization of the mucus model for a more extensive application seems possible and reasonable with respect to saving in vivo experiments with animals.

Animals↗

[Repeated intestinal exploration and multi-stage surgeries within the program of the treatment of segment necrosis and the small intestine ischemia].

An ischemic intestinal affection is observed frequently, its diagnosis difficult, mortality is high. In the clinic there were followed 47 patients with an ischemic intestinal affection. In 24 of them the etiology of ischemia was mesenterial thrombosis, in 23--strangulational ileus. While the doubt in intestinal viability existed, relaparotomy was performed for its state estimation and in necrosis-resection with primary anastomosis conduction. Mortality was 2.1%. Application of such a tactic had permitted to reduce significantly the frequency of resection conduction while doubt in intestinal viability present as well as mortality--in intestinal necrosis.

Acute Disease↗

Response of intestinal globule leucocytes in the mouse during a Trichinella spiralis infection and its independence of intestinal mast cells.

We have previously reported that intestinal mast cells represent a separate population of mast cells which is thymus- (T-) dependent. In this paper we examine whether the appearance of these cells is dependent on thymus-dependent antibodies or thymus serum factor(s). The response of intestinal mast cells and globule leucocytes to a Trichinella spiralis infection was therefore studied in congenitally athymic (nude) mice after treatment with specific anti-T. spiralis hyperimmune serum or normal mouse serum from thymus-bearing litter-mates. However, transfer of both types of serum did not lead to an intestinal mast cell response. It was concluded that the presence of an intact thymus or T-dependent cellular reactions and/or their products are essential for appearance of intestinal mast cells. In contrast infected athymic mice reacted with a minor reponse of globule leucocytes irrespective of the serum transfer. Occasionally metachromatic intra-epithelially located cells with toluidine-blue-positive granules, believed to be globule leucocytes, showed mitotic figures. Metachromatic cells were observed occasionally within the lumen of the gut. These data were interpreted as supporting the idea that the globule leucocyte is a cell sui generis and independent of the intestinal mast cell.

Animals↗

Tissue-specific expression of GM3(NeuGc) and GD3(NeuGc) in epithelial cells of the small intestine of strains of inbred rats. Absence of NeuGc in intestine and presence in kidney gangliosides of brown Norway and spontaneously hypertensive rats.

The ganglioside composition of the epithelial cells of the small intestine was investigated in 15 strains of inbred rats. Most of these strains had GM3 as the only detectable ganglioside. In addition to GM3, small amounts of GD3 were found in four strains, AVN, BN, DA, and LE. The fatty acid content of the ceramide portion was composed of a large, although variable, percentage of 2-hydroxy fatty acids. The sphingoid base was always C18-4D-hydroxysphinganine. The highly prominent sialic acid was N-glycolylneuraminic acid (NeuGc) in most strains. However in two strains, Brown Norway (BN) and spontaneously hypertensive rats (SHR), NeuAc was the only sialic acid of the gangliosides of the intestinal epithelium. The analysis of the ganglioside composition of the epithelium of the small intestine of the first generation hybrids of SHR with DA and BN, respectively, demonstrated that the expressions of GM3 (NeuGc) and GD3 were genetically transmitted as dominant traits and that BN and SHR were likely to carry the same deficient gene that led to the expression of GM3(NeuAc) instead of GM3(NeuGc) in the small intestine. For comparison, the sialic acid composition of kidney gangliosides was analyzed in some strains. 21-23% of the kidney gangliosides was GM3(NeuGc) in all tested strains, including BN and SHR. Therefore, the ganglioside composition of the intestinal epithelium could vary in the rat species, and the defect of N-glycolylneuraminic acid was not only strain-specific but also occurred in a tissue-specific way among strains of inbred rats.

Animals↗

The Golgi apparatus of rat small intestinal absorptive cells. I. Morphology and cytochemical staining pattern in proximal and distal small intestinal regions.

Comparative studies on the Golgi apparatus of rat small intestinal absorptive cells from duodenal, jejunal and ileal segments showed that the characteristic polarity of Golgi stacks is apparent along the entire small intestine; dilated cisternae containing lipoprotein particles are preferably localized at one Golgi side (cis face); narrow, regular cisternae predominate at the other side (trans face). Osmium deposits after prolonged osmification are restricted to cis Golgi cisternae. Pronounced differences between proximal and distal small intestinal regions exist in the cytochemical staining pattern of Golgi stacks after localization of thiamine pyrophosphatase, inosine diphosphatase and acid phosphatase. In duodenal and proximal jejunal absorptive cells demonstration of thiamine pyrophosphatase and inosine diphosphatase causes heavy deposits of reaction product over all Golgi cisternae; in the distal jejunum and in the ileum only 1-3 cisternae at the trans Golgi side are reactive. Similarly, the number of acid phosphatase-positive cisternae decreases from proximal to more distal small intestinal regions. Thiamine pyrophosphate, nucleoside diphosphatase and acid phosphatase are assumed to be active in glycosylation being involved in the removal of uridine diphosphate and other nucleoside phosphates (Tartakoff, 1980; Farquhar and Palade, 1981; Roth and Berger, 1982). Accordingly, the differences in the Golgi apparatus staining pattern after localization of these enzymes between proximal and distal small intestinal segments may reflect regional differences in the glycosylation of apoproteins in lipoprotein particles and in the kinetics of glycosylated plasma membrane and lysosomal constituents.

Acid Anhydride Hydrolases↗

Intestinal membrane calcium-binding protein. Vitamin D-dependent membrane component of the intestinal calcium transport mechanism.

A particulate fraction of rat intestinal mucosal homogenates, termed the "calcium-binding complex," contains three vitamin D-dependent activities: calcium binding of high affinity, calcium-dependent adenosine triphosphatase, and p-nitrophenylphosphatase. These particulate activities vary concordantly with intestinal calcium transport, suggesting that they represent membrane components of the translocation mechanism. The particulate was solubilized with 1-butanol and the activities were resolved partially by gel filtration and by DEAE-cellulose and spheroidal hydroxyl-apatite column chromatography. The Ca-binding activity was separated from the enzymes and isolated as a protein of molecular weight approximately 200,000, as estimated by gel filtration in 0.1% Triton X-100. The membrane protein, named IMCal (intestinal membrane calcium-binding protein), was dissociated with sodium dodecyl sulfate to yield a monomer of molecular weight 20,500 which is clearly distinguishable from the soluble calcium-binding protein (molecular weight 11,500) of rat mucosa. The apparent dissociation constants of Ca2+ of IMCal and of the soluble calcium-binding protein were estimated as 0.37 microM and 2.25 microM, respectively. The vitamin D-dependent activities of the calcium-binding complex are present in isolated intestinal microvillus membranes and may mediate the translocation of calcium from the intestinal lumen to the cytosol.

4-Nitrophenylphosphatase↗

Intestine-like remodeling of adult mouse glandular stomach by implanting of fetal intestinal mesenchyme.

A morphogenetic response of adult glandular stomach grown in contact with implanted fetal intestinal mesenchyme has been demonstrated. Mesenchymal tissues from intestines of 14- to 16-day-old BALB/c mouse fetuses were introduced beneath the epithelial layer of glandular stomach in 2-month-old mice and allowed to develop. Three to 4 weeks later, remodeling of the epithelial architecture had occurred; the characteristic glandular pit structure of normal stomach had been replaced by immature villi and crypts composed of mucus-secreting columnar cells more characteristic of intestinal tissues. Chief and parietal cells had disappeared, but neither goblet nor Paneth cells were observed. Such intestine-like morphogenesis was not induced by similarly implanted mesenchymal controls from fetal glandular stomach, forestomach, and salivary gland. A possible role of the mesenchymal stroma in the pathogenesis of intestinal metaplasia in stomach is discussed.

Aging↗

Regeneration in small intestine following exposure to X-radiation and neutron beam as estimated in the light of changes in alkaline phosphatase activity and degree of 3H-thymidine incorporation into cells in intestinal crypts.

Swiss mice were irradiated with X-rays (5, 7 and 9 Gy) and neutrons (3 and 5 Gy) determining the degree of 3H-thymidine incorporation into the cells in the intestinal crypts, alkaline phosphatase activity in intestinal homogenate and serum, and radiation-induced leucopenia. It was shown that damage to the cells in intestinal crypts depends on the dose and type of radiation. More radiation-resistant cells covering the intestinal villi showed a significant inhibition of alkaline phosphatase activity at high radiation doses. Changes in intestinal alkaline phosphatase activity were reflected also by changes in its level in the serum where its dependence on the dose of radiation was evident also.

Alkaline Phosphatase↗

[Unusual way of regenerating intestinal epithelium during seasonal intestinal transformation in Stichopus japonicus holothurians (possibility of an "external cambium")].

In Stichopus japonicus during summer months a profound morphofunctional rearrangement of the digestive tract resulting in its renovation is noted. It includes certain destructive-atrophic changes in the wall of the intestinal tube and some reparative processes accompanying them. In some species a spontaneous throwing out of the intestine with its subsequent restoration takes place. The mechanisms of the intestinal tube regeneration after its partial atrophy and after its spontaneous throwing out have much in common between them and with those previously described after an experimental throwing out. It is possible that under natural conditions (as well as under experimental ones) certain forms of wandering cells, migrating from the sublayers and/or from the surrounding structures (mesenterium and others), participate in the regenerative histogenesis of the intestinal epithelium. A suggestion is made that these cells are of coelomesodermal origin and play the role of the external cambium at sharp seasonal rearrangements of the holothurian intestinal tract.

Aging↗

[14C]glucosamine incorporation into intestinal glycoproteins by calf intestinal epithelium in organ culture.

The uptake and incorporation of [14C]glucosamine into secreted intestinal glycoproteins was examined in the calf intestinal mucosa and isolated epithelial cells, using an organ culture system. Incorporation varied with the area of the intestine, ie duodenum greater than jejunum greater than ileum. Secreted glycoproteins were examined after 3 and 24 hours in organ culture. Initially, a glycoprotein approximately 68,000 molecular weight (mol wt) was secreted by all areas of the intestine. This was followed by the appearance of a larger glycoprotein 10(6) to 10(7) mol wt. Enzymatic cleavage of jejunal brush borders released a glycocalyx glycoprotein similar in size to the secreted large mol wt glycoprotein. These similarities in mol wt are only suggestive evidence that the 2 large glycoproteins are the same. This procedure allows for the study of the maturation and development of a poorly understood component of the intestinal epithelial cell which has a wide range of functional considerations.

Animals↗

Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats.

Irinotecan hydrochloride (CPT-11), an antitumor camptothecin derivative, causes severe forms of diarrhea clinically. We characterized CPT-11-induced diarrhea histologically and enzymologically and assessed the relationships between intestinal toxicity and the activity of the enzymes that play a key role in the major metabolic pathway of CPT-11 in rats. CPT-11 (60 mg/kg i.v. for 4 days) induced intestinal toxicity characterized by severe chronic diarrhea, loss of body weight, and anorexia. Histological damage was most severe in the cecum. The segmental difference in the degree of the damage showed good correlation with the beta-glucuronidase activity in the contents of the lumen in each case, but not with the intestinal tissue carboxylesterase activity, which converts CPT-11 to its active form (7-ethyl-10-hydroxycamptothecin). Inhibition of the beta-glucuronidase activity in the intestinal microflora by antibiotics (1 mg penicillin and 2 mg streptomycin per ml of drinking water) markedly ameliorated the diarrhea and reduced cecal damage. Analysis of CPT-11 and its metabolites in the feces indicated that antibiotics completely inhibited the deconjugation of the glucuronic conjugate of 7-ethyl-10-hydroxycamptothecin by beta-glucuronidase. It is suggested that CPT-11-induced diarrhea would be attributable to the damage to the cecum, and that the inhibition of the beta-glucuronidase activity in the intestinal microflora is a major protective effect of antibiotics.

Animals↗

The intestinal mucosal barrier to intact antigenic protein. Difference between colon and small intestine.

The integrity of the normal mature intestinal mucosal barrier to unaltered proteins was evaluated with tritiated bovine albumin in rats. Intact H3-BSA placed into either colon or small intestinal lumen regularly reached the bloodstream in quantities sufficient to be antigenic or toxigenic, although the fraction of H3-BSA absorbed from the colon (0.13 per cent) was significantly smaller than that absorbed from the small intestine (1.7 per cent). These studies support the possibility that uptake of ingested or bacterial antigens from the normal gut may be involved in the pathogenesis of local intestinal and systemic disease in man.

Animals↗