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Kinetic characteristics of calcium absorption and secretion by rat colon.

The kinetic characteristics of calcium active transport in rat descending colon were determined by measuring unidirectional transmural calcium fluxes in vitro. The absorptive flux from mucosa to serosa (Jm leads to s) was saturable, with a calculated affinity (Kt) of calcium for the transport system of 1.6 mM and a maximal transport capacity (Vmax) of 133 nmol.cm-2.h-1. The administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increased Jm leads to s by increasing Vmax to 236 nmol.cm-2.h-1 without changing Kt (1.8 mM). The secretory flux from serosa to mucosa (Js leads to m) was not saturable and was not increased by 1,25(OH)2D3. Mannitol, a marker of transepithelial extracellular flux, underwent net absorption in the absence of electrochemical gradients, and its Jm leads to s and Js leads to m were not altered by 1,25(OH)2D3 administration. Addition of 11 mM D-glucose to the bathing medium consistently increased calcium Js leads to m and mannitol Jm leads to s and Js leads to m. Glucose reduced net calcium absorption except when sodium was removed from the medium. Calcium Js leads to m varied linearly with mannitol Js leads to m over the range of medium calcium from 0.125 to 5.0 mM. The behavior of calcium absorption by descending colon is compatible with a carrier-mediated, active-transport mechanism, whereas calcium secretion occurs by a nonsaturable process via a predominately paracellular pathway.

Animals↗

Colorectal transport during defecation in patients with lesions of the sacral spinal cord.

Normal defecation involves reflexes between the colorectum and sacral spinal cord. Lesions of the conus medullaris or cauda equina interrupt such reflex arches and cause constipation. The aim of the study was to compare colorectal transport during defecation in patients with sacral spinal cord lesions and healthy volunteers. Ten patients with sacral spinal cord lesions (six men and four women, age 21-57 y, median = 36) and 16 healthy volunteers (10 men and six women, age 22-42 y, median = 30) took one or two doses of 111In-labelled polystyrene pellets perorally to mark colorectal contents. Abdominal scintigraphy was performed before and after defecation. Total colorectal emptying and segmental antegrade or retrograde transport was computed. Median colorectal emptying during normal defecation was 81% of the rectosigmoid (range: 53% of the rectosigmoid to complete emptying of the rectosigmoid and 40% of the descending colon) in healthy volunteers and 27% of the rectosigmoid (range: 0-44% of the rectosigmoid) in patients with conal/cauda equina lesions (P < 0.001). Median antegrade transport was 82% (control group) vs 27% (patients) of the rectosigmoid (P < 0.001), 38% vs 4% of the descending colon (P < 0.02), 13% vs 1% of the transverse colon (P = 0.28), and 4% vs 2% of the caecum/ascending colon (P = 0.76). It is concluded that damage to reflex arches between the colorectum and the sacral spinal cord significantly reduces emptying of the rectosigmoid and descending colon during defecation.

Adult↗

Chemical and histochemical studies of normal and diseased human gastrointestinal tract. I. A comparison between histologically normal colon, colonic tumours, ulcerative colitis and diverticular disease of the colon.

Chemical and histochemical methods were used to compare the epithelial glycoproteins from formalin-fixed surgical specimens of normal human large intestine, colonic tumours, ulcerative colitis and diverticular disease. All the epithelial glycoproteins contained fucose, galactose, glucosamine, galactosamine and, in addition, sialic acids both with and without O-acyl substituents in the side chain and/or at position C4. The glycoproteins of the normal ascending and descending colons differed significantly with respect to the percentage of the sialic acids released following digestion of the de-O-acylated glycoprotein with Vibrio cholera neuraminidase and to the molar fucose-sialic acid ratio. Statistical analysis of the chemical data showed that (a) compared to normal, the sialic acids of the tumour and ulcerative colitis glycoproteins from the descending colon were significantly less substituted in the side chain and at position C4; (b) the O-acetyl substitution pattern of the sialic acids of the ulcerative colitis glycoproteins from the ascending colon and the quantitative composition of the carbohydrate prosthetic groups of the ulcerative colitis glycoproteins from both ascending and descending colons differed from normal; (c) it was not always possible to distinguish between the ulcerative colitis and tumour glycoproteins on the basis of the O-acetyl substitution pattern of their sialic acids; and (d), there were minor differences between normal glycoproteins and those from cases of diverticular disease.

Colitis, Ulcerative↗

Role of the rectosigmoidal junction in fecal continence: concept of the primary continent mechanism.

HYPOTHESIS: At mass contraction of the descending colon, the colonic contents stop at the sigmoid colon (SC) and do not pass directly to the rectum. We investigated the hypothesis that a continent mechanism seems to exist at the rectosigmoidal junction (RSJ), preventing the direct passage of stools from the descending colon to the rectum. METHODS: The SC in 16 healthy volunteers (mean +/- SD age, 38.6 +/- 10.2 years; 9 men and 7 women) was distended with an isotonic sodium chloride solution-filled balloon, and the pressure response of the RSJ and the rectum was recorded at rapid and gradual filling of the balloon. The test was repeated after the SC and RSJ were anesthetized separately. RESULTS: Rapid SC balloon distension with a mean +/- SD of 52.1 +/- 3.6 mL of isotonic sodium chloride solution effected an RSJ pressure increase to a mean +/- SD of 67.8 +/- 18.4 cm H(2)O (P<.01) with no rectal pressure response (P>.05). Slow SC filling produced a progressive increase in RSJ pressure but no rectal pressure change. At a mean +/- SD SC distending volume of 86.3 +/- 4.1 mL, the RSJ pressure decreased to 9.6 +/- 2.8 (P<.01), and the balloon was dispelled to the rectum; rectal pressure increased (P<.001), and the balloon was expelled to the exterior. The RSJ pressure did not respond to distension of the anesthetized SC. CONCLUSIONS: Contraction of the RSJ at rapid SC distension with big volumes implies a reflex relationship that we call the RSJ guarding reflex. This reflex seems to prevent the descending colon contents from passing directly to the rectum. It is considered the first continent reflex and may serve as an investigative tool in the study of fecal incontinence.

Adult↗

Distinguishing right from left colon by the pattern of gene expression.

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.

Adult↗

Methylation of intestinal and hepatic DNA in rats treated with methylazoxymethanol acetate.

Descending colon is the most sensitive segment of rat intestine and is at least as sensitive as liver to the carcinogenic effects of methylazoxymethanol acetate. To determine whether a relationship exists between tumor induction and level of DNA methylation, we measured the levels of 7-methylguanine in the DNA isolated from duodenum, descending colon, and liver of rats treated with this carcinogen. Because radiolabeled methylazoxymethanol acetate is not available, we utilized high pressure liquid chromatography whereby methylated purines could be detected in amounts as little as 100-300 pmoles. DNA isolated from liver of carcinogen-treated rats had significant amounts of 7-methylguanine. On the contrary, DNA isolated from descending colon of rats treated with methylazoxymethanol acetate had minimal amounts of 7-methylguanine; these data suggest that the level of 7-methylguanine does not correlate with sensitivity to tumor induction by methylazoxymethanol acetate.

Animals↗

Prevention of spontaneous and chemically induced carcinogenesis using activated carbon fiber adsorbent. III. Inhibitory effect of the activated carbon fiber adsorbent 'Aqualen' on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in rats.

Two-month-old outbred female LIO rats were exposed weekly to 15 (experiment I, groups 1, 2 and 3) or to 5 (experiment II, groups 4, 5 and 6) subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen, the rats from groups 2, 3, 5 and 6 were given Aqualen in their diet. In both experiments rats were fed Aqualen five times per week together with lab chow at the daily dose of 0.1 g/kg (groups 2 and 5) or 1.0 g/kg (groups 3 and 6) of body weight. Additionally, other rats were not exposed to the carcinogen and served as an intact control (group 7) or were given Aqualen with the diet at the daily dose of 0.1 g/kg (group 8) or 1.0 g/kg (group 9). These experiments were finalized 6 months after the first injection of DMH. In experiments I and II, the majority of tumors were localized in the descending colon. Tumors of the small intestines developed only in rats from experiment I. The total incidence of colon tumors as well as tumors in different parts of the colon and the mean number of tumors per rat were much higher in rats from all groups in experiment I than in the rats from experiment II. In experiment I supplementation of Aqualen to the diet was followed by a decrease in the incidence of tumors in the ascending colon and by a decrease in the number of tumors per rat in both ascending and descending colons regardless of the dose of the enterosorbent. In experiment II the effect of Aqualen was stronger than in experiment I -- the enterosorbent decreased both the tumor incidence and the multiplicity in the total colon, its ascending and descending parts and in the rectum. In experiments I and II the percentage of small colon tumors among rats exposed to Aqualen (groups 2, 3, 5 and 6) was higher than that of the controls (groups 1 and 4). Most of detected intestinal tumors were classified as adenocarcinomas. The level of tumor differentiation was higher in rats exposed to Aqualen. There were no pathological changes observed in rats exposed to Aqualen without DMH. Carcinogen treatment resulted in an increase of serum glucose and cholesterol levels whereas Aqualen normalized these changes. Thus, our results demonstrate the inhibitory effect of activated carbon fiber adsorbent Aqualen on intestinal carcinogenesis in rats.

1,2-Dimethylhydrazine↗

Colonic motility and tone after spinal cord and cauda equina injury.

AIM: To characterize colonic motility and tone in patients with spinal cord and cauda equina injury. METHODS: Barostat-controlled measurements of tone and manometric measurements of phasic contractions in the left colon in two patients with spinal cord injury. ANALYSIS: Computer based analysis of tone and phasic activity; comparison with data from 11 healthy subjects. RESULTS: Both patients showed normal fasting tone and decreased postprandial tone in the colon; one had markedly decreased phasic contractility in the descending colon, but both had normal sigmoid colon motility. CONCLUSIONS: Impaired postprandial tone and phasic motor function of the descending colon after spinal cord injury with normal sigmoid motility suggests regional differences in the effect of denervation. The effect of the level of injury to the neural axis on colonic motor and sensory function requires further elucidation.

Adult↗

Infrarenal aortic occlusion, colonic blood flow, and the effect of nitroglycerin afterload reduction.

Colonic ischemia has been reported to occur in 1% to 13% of all cases of aortic reconstruction. To examine intestinal blood flow in aortic occlusion, three groups of dogs were subjected to measurement of hemodynamic parameters and mesenteric blood flow. Group I served as a control group, while group II underwent balloon catheter occlusion of the infrarenal aorta. Group III received intravenous nitroglycerin infusion during and after aortic occlusion. There was no statistically significant change in intestinal blood flow in group I. Small bowel mucosal blood flow fell in group II. Small bowel serosal blood flow was preserved but total small bowel and small bowel mucosal values fell sharply in group III. Ascending and descending colonic blood flow was unaltered in group I but fell significantly in groups II and III. After restoration of normal aortic circulation, small bowel mucosal flow remained significantly below baseline in groups II and III. Ascending and descending colonic blood flow also remained depressed in groups II and III. Both mucosal and serosal blood flow fell and serosal values remained constant in group III. Both groups exhibited decreased total, mucosal, and serosal blood flow in the descending colon after release of the aortic occlusion. These data show that temporary infrarenal aortic occlusion causes significant changes in intestinal blood flow. The mechanism is due to persistent autoregulatory vasoconstriction. Nitroglycerin used for afterload reduction in aortic reconstruction does not ameliorate decreases in intestinal blood flow and may actually shunt blood away from the distal colon and the distal intestinal mucosa during aortic occlusion.

Animals↗

Nicotinic acid action on gastrointestinal smooth muscle.

The mechanism of nicotinic acid action in smooth muscle was studied by testing the drug in rat stomach fundus and descending colon using either the superfusion or perfusion technique. In the rat stomach strips nicotinic acid (or Na-nicotinate) induces concentration-dependent contractions that are drastically antagonized by indomethacin but not by the other inhibitors tested (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine, imidazole, anacardic acid). Reduced glutathione, on the contrary, clearly potentiates the contractile effect of nicotinic acid in the tissue. The response of the rat stomach strips to different prostanoids (PGE1, PGE2 alpha, PGF2 alpha, and PGI2) shows that only PGE2 (at a very low concentration: 14 nM) induces muscle contraction similar to that evoked by Na-nicotinate (34.4 nM). In segments of rat descending colon Na-nicotinate induces concentration-dependent contractions that are abolished by scopolamine, by hemicholinium-3 or incubation at low temperature (20 degrees C). These results provide evidence that nicotinic acid influences gastrointestinal smooth muscle by indirect mechanisms, i.e. by release of endogenous autacoids, namely prostaglandins in the stomach fundus and cholinergic transmitter in the descending colon.

Animals↗

Pressure response of human colon to intraluminal distension.

Pressure response to intraluminal distension was recorded in the ascending and descending colon of six subjects awaiting closure of transverse colostomies to assess and compare compliance in different regions of the human colon. Resistance to distension was significantly greater in the descending colon at intraluminal volumes of 30 ml or greater (P less than 0.01). An equal number of postmortem studies, representing passive connective tissue resistance, demonstrated a similar but more pronounced difference (P less than 0.001), which was maintained after correction for initial intraluminal diameter differences (P less than 0.001). The differences between in vivo and postmortem results indicated an active muscular component in the response of the ascending colon to distension compared with a totally passive distal response. These results support the concept of a functional division in the human colon.

Colon↗

The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats.

1. The mitotic rate in the crypts of Lieberkühn of the descending colon and in dimethylhydrazine-induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique. 2. Intraperitoneal injection of a small dose (10 microgram/kg) of serotonin resulted in an increase in the tumour cell mitotic rate. 3. Blockade of serotonin receptors by 2-bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL-6-fluorotryptophan both result in a decrease in the tumour cell mitotic rate. 4. Treatment with serotonin, 2-bromolysergic acid diethylamide and DL-6-fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.

Adenocarcinoma↗

Study of kinetics of epithelial cell populations in normal tissues of the rat's intestines and in carcinogenesis. III. Changes in kinetics of enterocyte populations in the course of experimental intestinal tumour induction in rats.

A stage-by-stage study of disturbances in enterocyte proliferation in the ileum and descending colon in the course of tumour induction by treatment with 1,2-dimethylhydrazine was performed. Even at early stages, an expansion of the zone of epithelial cell proliferation in the crypts and migration of dividing cells as far as to the crypt mouth, which is a manifestation of enterocyte differentiation disturbances, were observed. Enterocytes of the crypts chiefly proliferated through a short cycle, the mean duration of which was slightly greater than in normal intestinal tissue. The reduced cell loss in the epithelium and resultant disturbances of its steady state led to the accumulation of great numbers of atypical cells in the superficial layers of the crypts and formation of carcinomas in situ in the descending colon. The microscopically unaltered sections of the mucosa, prior to development of overt neoplastic changes carcinomas in situ, superficial cancers and small-size adenocarcinomas revealed a simplified structure of enterocyte population, as compared with normal epithelium. As tumours progressed, the heterogeneity of its component cell subpopulations increased, and several subpopulations, differing in mean duration of the mitotic cycle, were formed. Pathologic mitoses made up a greater portion (50-60 per cent) of the dividing cells of the descending colon, as compared with ordinary 4 per cent at all stages of experimental tumour induction.

1,2-Dimethylhydrazine↗

Cell death (apoptosis) in mouse intestine after continuous irradiation with gamma rays and with beta rays from tritiated water.

Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed dose from HTO, the water content both of the mouse body and of the cells was assumed to be 70%. One megabecquerel of HTO per mouse (i.e., 40 MBq/kg body wt) gave a dose rate of 0.131 mGy/h. The mean lethal doses (D0) were calculated for gamma rays and HTO, and relative biological effectiveness values of HTO relative to gamma rays were obtained. The D0 values for continuous irradiation with gamma rays were 210 mGy for small intestine and 380 mGy for descending colon, and the respective values for HTO were 130 and 280 mGy, indicating the high radiosensitivity of target cells for apoptotic death. The relative biological effectiveness of HTO relative to 137Cs gamma rays for cell killing in both the small intestine and the descending colon in the mouse was 1.4-2.1.

Animals↗

Depth of insertion at flexible sigmoidoscopy: implications for colorectal cancer screening and instrument design.

BACKGROUND AND STUDY AIMS: The depth of insertion at flexible sigmoidoscopy is variable, depending upon bowel preparation, patient tolerance and distal colonic anatomy. Many endoscopists routinely aim to insert the 60 cm flexible sigmoidoscope to the splenic flexure; however internal endoscopic markers are unreliable, making the true anatomical extent of the examination difficult to assess. The aim of this study was to assess the depth of insertion at flexible sigmoidoscopy. PATIENTS AND METHODS: Two separate studies were done. In the first (study 1), magnetic endoscopic imaging was used to determine the final depth of insertion at non-sedated, screening flexible sigmoidoscopy. In the second (study 2), "real-time" imaging was utilized to determine sigmoid looping and the anatomical location of the endoscope tip after 60 cm of instrument had been inserted during total or limited colonoscopy. A total of 117 consecutive average-risk patients, aged 55-65 years participated in study 1, and 136 patients underwent either limited, (33) or attempted total colonoscopy (103) in study 2. RESULTS: In study 1 the median insertion distance was 52 cm, range 20-58. In 61 % of patients the imaging system showed that the descending colon had not been visualized by the end of the procedure. Failure to reach the sigmoid/descending junction occurred in 29 (24%) patients. Reasons for failure included poor tolerance of the procedure due to pain (23 patients) inadequate preparation (3 patients) and, excessive looping (3 patients). In study 2, after 60 cm of instrument had been inserted, the splenic flexure or beyond was reached in 29% and the descending colon in 9%, whilst in 62 % the endoscope tip had not passed beyond the sigmoid/descending colon junction. A sigmoid loop formed in 70% of patients, and unusual loops such as the alpha, reverse alpha and reverse sigmoid spiral loop occurred more frequently in women compared to men (P = 0.0249). In those 104 patients where the splenic flexure was reached the mean maximum length of instrument inserted prior to reaching the flexure was 75.4 cm, (SD = 21.9). CONCLUSIONS: Examination of the entire sigmoid was not achieved in approximately one-quarter of patients undergoing screening flexible sigmoidoscopy, mainly because of discomfort. The descending colon is intubated in a minority of cases (using standard instruments), even after 60 cm has been inserted. Alternative instruments with different shaft characteristics (floppy, narrow calibre, 80-100 cm in length) may be necessary to ensure deeper routine intubation in nonsedated patients.

Aged↗

Free amino acids in biopsy specimens from the human colonic mucosa.

The content of free amino acids and total protein was determined in endoscopic biopsy specimens from the rectum, descending colon, transverse colon, and ascending colon in 10 patients. The amino acids were quantified by ion-exchange chromatography and were detected by fluorescence. The amino acid pattern and the rank order of the individual amino acids in the colon were different compared to those in plasma. Glutamate, taurine, aspartate, glutamine, glycine, alanine, serine, lysine, valine, and ornithine were the 10 most abundant amino acids in the colon. The rank order was the same in all of the different segments of the colon. The concentrations of the amino acids decreased the more aborally the biopsies were taken. The protein content in the rectum was significantly lower than that in the transverse colon, but there were no difference between the different segments otherwise. The study demonstrated the possibility of determining free amino acids from endoscopic biopsies of human colonic mucosa. Biopsy specimens from the descending colon and/or rectum/sigmoid colon may be considered representative of the entire large intestine. The technique may be used for repeated sampling in studies of the amino acid metabolism of the intestinal mucosa.

Aged↗

Position changes improve visibility during colonoscope withdrawal: a randomized, blinded, crossover trial.

BACKGROUND: Adequate distension is essential to maximize neoplasia detection during colonoscope withdrawal. Position changes may improve distension but are often not performed in routine practice. OBJECTIVE: To assess whether routine position changes improve luminal distension during colonoscope withdrawal. DESIGN: Randomized, blinded, crossover trial. SETTING: Single tertiary-referral center, United Kingdom. PATIENTS: Fourteen patients attending for routine colonoscopy. INTERVENTIONS: Videotaped, back-to-back examination of colon proximal to rectosigmoid junction in left lateral position only, then with position changes: left lateral for the cecum to the hepatic flexure, supine for the transverse colon, and right lateral for the splenic flexure and the descending colon, or vice versa. MAIN OUTCOME MEASUREMENTS: Luminal distension as scored by a blinded video reviewer. Luminal distension was scored on a scale of 1 to 5 for each colonic area: 1, complete collapse; 5, widely distended to limit of view. A score of 2 or less was considered inadequate for diagnosis. RESULTS: Scores for the 2 examinations from the blinded video reviewer were significantly higher in the transverse, the splenic flexure, and the descending colon, P = .02, .002, and <.001, respectively. Without position changes, 6 of 14 of patients (43%) would have had a nondiagnostic distension score (1 or 2) in at least 1 colonic area, P = .03. LIMITATIONS: Nonvalidated scoring system for luminal distension, however, good agreement between endoscopist and blinded reviewer, weighted kappa 0.53, 95% confidence interval 0.38-0.69. CONCLUSIONS: Position change, a cost-neutral intervention, during colonoscope withdrawal improved luminal distension between hepatic flexure and sigmoid-descending junction and has the potential to reduce adenoma and early cancer miss rates.

Colon↗

Partial colonic obstruction following ovariohysterectomy: a report of three cases.

Partial extramural obstruction of the descending colon was diagnosed in two dogs and a cat as a complication of elective ovariohysterectomy. In each case, the obstruction was caused by fibrous tissue that encircled or crossed the descending colon, severely restricting the organ's normal mobility and luminal diameter. Clinical signs secondary to obstipation were observed in two cases, five weeks and 27 months after elective ovariohysterectomy. In one dog without clinical signs, the adhesion was an incidental finding during a laparotomy performed nine years after the ovariohysterectomy. The fibrous adhesions were removed surgically in all three cases without additional complications.

Animals↗