A smooth muscle tone-dependent stretch-activated migrating motor pattern in isolated guinea-pig distal colon.
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We have investigated the tone dependence of the intrinsic nervous activity generated by localized wall distension in isolated segments of guinea-pig distal colon using mechanical recordings and video imaging of wall movements. A segment of colon was threaded through two partitions, which divided the colon for pharmacological purposes into oral, stimulation and anal regions. An intraluminal balloon was located in the stimulation region between the two partitions (12 mm apart). Maintained colonic distension by an intraluminal balloon or an artificial faecal pellet held at a fixed location generated rhythmic (frequency 0.3 contractions min(-1); duration approximately 60 s) peristaltic waves of contraction. Video imaging of colonic wall movements or the selective application of pharmacological agents suggested that peristaltic waves originated just oral (< or = 4 mm) to the pellet and propagated both orally (approximately 11 mm s(-1)) and anally (approximately 1 mm s(-1)). Also, during a peristaltic wave the colon appears to passively shorten in front of a pellet, as a result of an active contraction of the longitudinal muscle oral to the pellet. Faecal pellet movement only occurred when a rhythmic peristaltic wave was generated. Rhythmic peristaltic waves were abolished in all regions by the smooth muscle relaxants isoproterenol (1 microM), nicardipine (1 microM) or papavarine (10 microM), and by the neural antagonists tetrodotoxin (TTX; 0.6 microM), hexamethonium (100 microM) or atropine (1 microM), when added selectively to the stimulation region. Nicardipine, atropine, TTX, or hexamethonium (100 microM) also blocked the evoked peristaltic waves when selectively added to the oral region. Nomega-nitro-L-arginine (L-NA; 100 microM) added to the anal region reduced the anal relaxation but increased the anal contraction, leading to an increase in the apparent conduction velocity of each peristaltic wave. In conclusion, maintained distension by a fixed artificial pellet generates propulsive, rhythmic peristaltic waves, whose enteric neural activity is critically dependent upon smooth muscle tone. These peristaltic waves usually originate just oral to the pellet, and their apparent conduction velocity is generated by activation of descending inhibitory nerve pathways. (
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Distinguishing right from left colon by the pattern of gene expression.
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Distinct epidemiological and clinicopathological characteristics of colorectal carcinomas (CRCs) based on their anatomical location suggest different risk factors and pathways of transformation associated with proximal and distal colon carcinogenesis. These differences may reflect distinct biological characteristics of proximal and distal colonic mucosa, acquired in embryonic or postnatal development, that determine a differential response to uniformly distributed environmental factors. Alternatively, the differences in the epidemiology of proximal and distal CRCs could result from the presence of different procarcinogenic factors in the ascending versus descending colon, acting on cells with either similar or distinct biological characteristics. We applied cDNA microarray technology to explore the possibility that mucosal epithelium from adult proximal and distal colon can be distinguished by their pattern of gene expression. In addition, gene expression was studied in fetal (17-24 weeks gestation) proximal and distal colon. More than 1000 genes were expressed differentially in adult ascending versus descending colon, with 165 genes showing >2-fold and 49 genes showing >3-fold differences in expression. With almost complete concordance, biopsies of adult colonic epithelium can be correctly classified as proximal or distal by gene expression profile. Only 87 genes were expressed differently in ascending and descending fetal colon, indicating that, although anatomically relevant differences are already established in embryonic colon, additional changes in gene expression occur in postnatal development. (
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Mechanisms involved in carbachol-induced Ca(2+) sensitization of contractile elements in rat proximal and distal colon.
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1. Mechanisms involved in Ca(2+) sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied. 2. In alpha-toxin-permeabilized preparations from the rat proximal and distal colon, Ca(2+) induced a rapid phasic and subsequent tonic component. After Ca(2+)-induced contraction reached a plateau, guanosine 5'-triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparations of both the proximal and distal colon (Ca(2+) sensitization). Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced Ca(2+) sensitization more significantly in the proximal colon than in the distal colon. 3. Y-27632 at 10 microm had no effect on Ca(2+)-induced contraction or slightly inhibited phorbol-12,13-dibutyrate-induced Ca(2+) sensitization in either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor, inhibited GTP plus CCh-induced Ca(2+) sensitization in the distal colon, but not in the proximal colon. The component of Ca(2+) sensitization that persisted after the chelerythrine treatment was completely inhibited by Y-27632. 4. In beta-escin-permeabilized preparations of the proximal colon, C3 exoenzyme completely inhibited GTP plus CCh-induced Ca(2+) sensitization, but PKC(19-31) did not. In the distal colon, C3 exoenzyme abolished GTP-induced Ca(2+) sensitization. It inhibited CCh-induced sensitization by 50 % and the remaining component was inhibited by PKC(19-31). 5. These results suggest that both protein kinase C and rho pathways in parallel mediate the Ca(2+) sensitization coupled to activation of muscarinic receptors in the rat distal colon, whereas the rho pathway alone mediates this action in the proximal colon. (
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Proximal versus distal hyperplastic polyps of the colorectum: different lesions or a biological spectrum?
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BACKGROUND: Because of their suggested link with microsatellite instability high colorectal cancers, right sided hyperplastic polyps (HPs) may differ from their distally located counterparts. This is highlighted by the recognition of a variant HP, termed sessile serrated adenoma (SSA), which predominates in the proximal colon. HPs displaying the morphological features now associated with SSAs have been shown to have altered expression of "cancer associated" markers, but no studies have investigated whether this is dependent on anatomical location of the polyps. AIMS: To evaluate morphological and functional features in right versus left sided HPs from patients without colorectal cancer with the aim of identifying distinguishing characteristics. METHODS: HPs originating in the proximal and distal colorectum were histochemically and immunohistochemically stained to evaluate a panel of markers related to proliferation and differentiation. In addition, a series of morphological features was evaluated for each polyp. RESULTS: Crypt serration, crypt dilatation, and horizontal crypt growth were more common among HPs from the right side, whereas histochemical factors including mucin changes, global methylation status, and expression of carcinoembryonic antigen were not significantly different. An age disparity was also seen between patients with right versus left sided lesions, with patients with right sided lesions being an average of more than 10 years younger than those with left sided lesions. CONCLUSIONS: These findings suggest that right and left sided HPs differ mainly in terms of growth regulation rather than cellular differentiation, implying that these lesions belong to a continuous spectrum of serrated polyps that differ quantitatively rather than qualitatively. (
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Rectosigmoid findings are not associated with proximal colon cancer: analysis of 6 196 consecutive cases undergoing total colonoscopy.
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AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy. METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (mean age 60 years, 65% males, without prior history of colorectal examination). Neoplasms were classified as diminutive adenoma (5 mm or less), small adenoma (6-9 mm), advanced adenoma (10 mm or more, with villous component or high-grade dysplasia) and cancer (invasive adenocarcinoma). The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal colon (from cecum to descending colon). RESULTS: The trend of the prevalence of advanced proximal adenoma was to increase with severe rectosigmoid findings, while the prevalence of proximal colon cancer did not increase with severe rectosigmoid findings. Among the 157 patients with proximal colon cancer, 74% had no neoplasm in the rectosigmoid colon. Multivariate logistic-regression analysis revealed that age was the main predictor of proximal colon cancer and existence of rectosigmoid adenoma was not a predictor of proximal colon cancer. CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening, especially in older populations. (
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Withdrawing method of the stiffening tube incidentally inserted into the descending colon.
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We experienced a very rare complication of colonoscopy, a migration of stiffening tube into the colorectum. We herein introduce a withdrawing method of migrating stiffening tube incidentally inserted into the colorectum. A 65-year-old Japanese woman underwent colonoscopy because of abdominal discomfort. We used stiffening tube to insert the scope to the proximal colon because of her redundant sigmoid colon. When withdrawing the scope, we realized that the tube was fully inside the colorectum. We could not remove the tube instantly, and it reached the splenic flexure, finally. We reinserted the scope through the migrating tube, straightened the scope, and withdrew it holding a slight angle of the scope over the proximal end of the tube. Then, we could safely remove the tube along with the scope through the anus. (
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Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa.
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BACKGROUND: Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon. METHODS: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods. RESULTS: Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon. CONCLUSION: The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon. (
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Comparative study of descendent colon rupture resistance considering traction force of rupture and total energy of rupture in rats.
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PURPOSE: To compare total energy of rupture and traction force of rupture tests within a rupture resistance study of descendent colon of rats. METHODS: Twelve descendent colon segments of rats were considered to perform the study. For each one of the specimens, total energy of rupture and traction force of rupture necessary to promote colic wall burst were evaluated through the biomechanical total energy of rupture test using the Biomechanical Data Acquisition and Analysis System, version 2.0. Average, standard deviation, standard error of average and coefficient of variation were considered for analysis of results. RESULTS: Traction force of rupture average, standard deviation, standard error of average and coefficient of variation were 380.05 gf, 98.74, 28.5 e 25.98%, respectively while total energy of rupture presented average of 244.85 gf, standard deviation of 57.76, standard error of average of 16.67 and coefficient of variation of 23.59. CONCLUSION: Although, total energy of rupture considered a larger number of attributes to its calculation related to non-linear viscoelastic materials, such as colic wall, it presented a smaller coefficient of variation when compared to traction force of rupture, thus demonstrating to constitute a possible parameter to analyze intestinal resistance of rats. (
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