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Relationships among sodium current, permeability, and Na activities in control and glucocorticoid-stimulated rabbit descending colon.

Effects of a potent synthetic glucocorticoid, methylprednisolone (MP), on transepithelial Na transport were examined in rabbit descending colon. Current-voltage (I-V) relations of the amiloride-sensitive apical Na entry pathway were measured in colonic tissues of control and MP-treated (40 mg im for 2 days) animals. Tissues were bathed mucosally by solutions of various Na activities, (Na)m, ranging from 6.2 to 75.6 mM, and serosally by a high K solution. These I-V relations conformed to the "constant field" flux equation permitting determination of the permeability of the apical membrane to Na, PmNa, and the intracellular Na activity, (Na)c. The following empirical relations were observed for both control and MP-treated tissues: Na transport increases hyperbolically with increasing (Na)m obeying simple Michaelis-Mentin kinetics; PmNa decreased hyperbolically with increasing (Na)m, but was unrelated to individual variations in (Na)c; (Na)c increased hyperbolically with (Na)m; both spontaneous and steroid-stimulated variations in Na entry rate could be attributed entirely to parallel variations in PmNa at each mucosal Na activity. Comparison of these empirical, kinetic relations between control and MP-treated tissues revealed: maximal Na current and PmNa were greater in MP tissues, but the (Na)m's at which current and PmNa were half-maximal were markedly reduced; (Na)c was significantly increased in MP tissues at each (Na)m while the (Na)m at half-maximal (Na)c was unchanged. These results provide direct evidence that glucocorticoids cause marked stimulation of Na absorption across rabbit colon primarily by increasing the Na permeability of the apical membrane. While the mechanism for the increased permeability remains to be determined, the altered relation between PmNa and (Na)m suggests possible differences in the conformation or environment of the Na channel in MP-treated tissues.

Animals↗

Age-related loss of nongoblet crypt cells parallels decreased secretion in rabbit descending colon.

The effects of aging on active electrolyte transport and epithelial cell morphology were studied in rabbit descending colon. The rate of electrolyte transport was determined using the voltage-clamp technique, while computerized morphometric techniques were used to describe age-related and secretion-induced changes in histology. Comparison of percent water content of fecal pellets between young (2-3 mo) and mature (3.5-5 yr) animals demonstrated that mature animals had significantly decreased percent stool water. In mature animals, the total number of crypt epithelial cells was significantly less than in young animals, primarily due to the loss of crypt nongoblet cells. Crypt goblet cell number and area were not significantly changed from young to mature, while the crypt nongoblet cell number and area declined 38 and 28%, respectively, in the mature colon. Theophylline elicited dilatation of the crypt lumen. The decreased crypt nongoblet cell area correlated with a decreased theophylline-induced Cl- secretory response observed in the mature colon as measured by the change in short-circuit current (Isc). Also, a significant decrease in theophylline-stimulated active Cl- secretion was observed in mature vs. young animals in the presence of mucosal barium (5 mM) to eliminate active K+ secretion. The maximum theophylline plus barium-induced increase in Isc in young colon was 3.4 +/- 0.3 mueq.cm-2.h-1 and in mature colon 2.5 +/- 0.3 mueq.cm-2.h-1 (P less than 0.05). No significant difference in basal Isc and amiloride-inhibitable Na+ absorption was found between young and mature animals. The decreased capacity to secrete Cl- and the decrease in number and area of crypt nongoblet cells corresponds with the decrease in percent water content of mature fecal pellets.

Aging↗

The effect of estrogen on epithelial cell proliferation and differentiation in the crypts of the descending colon of the mouse: a radioautographic study.

The regulatory role of estrogen on cell population kinetics in the descending colon was studied in intact female and ovariectomized mice. In the colonic crypts from intact mice, the crypt size (the number of epithelial cells per crypt column) and the proliferative activity of epithelial cells fluctuated slightly during the estrous cycle. Peak cellularity per crypt column was exhibted during estrus and early diestrus, whereas peaks in labeling index were seen during estrus and late metestrus. While the population size of mucous cells showed a minimal variation, the number of proliferative vacuolated cells per crypt column varied inversely with that of differentiated columnar cells during estrous cycle. The vacuolated cells were increased in number in the preovulatory phase and the columnar cells in the postovulatory phase. Three weeks after bilateral ovariectomy, the colonic crypt appeared to reach a new steady state, which was characterized by a small crypt size, a decrease in the number of differentiated cells, an increase in the relative number of proliferative cells and a relative increase in the proliferative activity of the crypt as compared to intact mice. When ovariectomized mice were treated with estrogen, the number of 3H-thymidine-labeled cells in the crypt was decreased as compared to untreated ovariectomized mice, the decrease being greater after a single injection than after multiple injections of estrogen, and the vacuolated-columnar cell line being affected more than mucous cell line. Meanwhile, the crypt size as well as the population size of differentiated cells in the crypt failed to return to normal after estrogen treatments. Thus, estrogen did not promote differentiation of epithelial cells in the crypt.

Animals↗

Sd(a)-antigen-like structures carried on core 3 are prominent features of glycans from the mucin of normal human descending colon.

This paper describes structural characterization by NMR, MS and degradative studies of mucin glycans from normal human descending colon obtained freshly at autopsy. The saccharides were mainly based on core 3 (GlcNAcbeta1-3GalNAc). Among the terminal saccharide determinants Sd(a)/Cad-antigen-like structures were prominent, and Lewis x, sialyl Lewis x and sulphated Lewis x were found as minor components, whereas blood group H and A antigenic determinants were absent. The saccharides were markedly different from those of mucins from colon cancers or colon cancer cell lines analysed so far, in which cores 1 and 2 are prominent features, and in which various other terminal determinants have been found, but not Sd(a)/Cad.

Autopsy↗

[A case of resected spinal metastasis following colectomy and hepatectomy for descending colon carcinoma].

The patient was a 49-year-old man. In 1995, he underwent left hemicolectomy for descending colon carcinoma, and in 1996, partial hepatic resection was performed for liver metastasis. Post-operative chemotherapy was performed with 5'-DFUR. Five years later, he had lumbar and femoral pain. X-ray and MRI examination revealed a compression fracture and a spinal tumor at the XII thoracic vertebra. Though chemoradiotherapy was performed, the symptoms of pain, numbness and muscle weakness progressed. A resection of the metastatic spinal tumor was performed. Following several systemic chemotherapies, such as 5-FU/l-LV, CPT-11 + 5-FU/l-LV and low-dose CPT-11/UFT, radiotherapy was performed for the progressed bone tumor. At 2 years after surgery, he is still able to walk and no other site of recurrence has been detected.

Adenocarcinoma↗

Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflection. II. Antimesenteric wall ascending and descending colon and cecum.

From 1970 to 1981, 50 patients had curative surgery for carcinoma of the cecum, ascending, or descending colon and were Stage greater than or equal to B2. In 15 cases, the lesion originated on the antimesenteric (posterolateral) bowel wall. Of seven cases (with minimum three-year follow-up) not receiving adjuvant postoperative regional irradiation, four recurred in the tumor bed/abdominal wall versus 0/3 irradiated patients. Similarly, the five-year survival was improved in the irradiated group (2/3) versus only 2/9 in the unirradiated group. Patients with transmural extension of right or left colon cancers originating on the anti mesenteric (posterolateral) bowel wall may have a high incidence of postoperative regional failure which may be decreased by adjuvant postoperative regional irradiation.

Adenocarcinoma↗

Myenteric neurons of the rat descending colon: electrophysiological and correlated morphological properties.

Conventional intracellular electrophysiological recordings were made from 502 myenteric neurons of the rat descending colon. Myenteric neurons could be classified into three groups on the basis of distinct electrophysiological properties. The first group of neurons (51% of all neurons) fired tetrodotoxin-sensitive action potentials in response to direct somal depolarization and the majority (98%) of this group generated fast cholinergic excitatory synaptic potentials in response to focal stimulation and were therefore designated S/Type 1 neurons. The second group (40%) of neurons fired tetrodotoxin-insensitive action potentials which were followed by long-lasting membrane afterhyperpolarizations, hence were termed AH neurons. These neurons did not receive fast cholinergic synaptic inputs but ionophoretic application of acetylcholine induced rapid nicotinic cholinoceptor-mediated depolarizations. The final group of neurons (9%), named Type 3 neurons, received fast cholinergic synaptic inputs but could never be made to fire action potentials. Rundown in amplitude of successive fast excitatory synaptic potentials evoked by a short train of presynaptic nerve stimuli was observed in only a small proportion of neurons (8/37; 22%) with the majority of neurons (29/37; 78%) showing no such decrease in amplitude, even at frequencies of stimulation as high as 10 Hz. Superfusion of 5-hydroxytryptamine could induce both an inhibition and a facilitation of cholinergic fast synaptic transmission. Evidence was adduced that these presynaptic inhibitory and facilitatory actions appeared to be mediated via 5-hydroxytryptamine 1A and 5-hydroxytryptamine 4 receptors, respectively. Muscarinic slow excitatory synaptic potentials were not detected (9/9 neurons tested) and non-cholinergic slow excitatory synaptic potentials following repetitive focal presynaptic nerve stimulation were observed in only 39/502 (8%) of all neurons. In those neurons in which a demonstrable change in membrane input resistance was detectable, slow excitatory potentials were accompanied by an increased input resistance. In addition, in a small subset (4%) of S/Type 1 neurons, slow membrane hyperpolarizations accompanied by an increased membrane input resistance were observed following tetanic presynaptic nerve stimulation. Superfusion of 5-hydroxytryptamine induced both membrane depolarizations and hyperpolarizations. Membrane depolarizations were observed in 40% of all neuronal types (34% of S/Type 1 neurons, 58% of AH neurons and 11% of Type 3 neurons) and were accompanied by an increased membrane input resistance and occasionally, in S/Type 1 and AH neurons, by anodal break excitation or spontaneous action potential firing. Membrane hyperpolarizations were observed in S/Type 1 neurons (5%) only and were accompanied, unexpectedly, by an increased membrane input resistance. In those neurons that responded both to application of 5-hydroxytryptamine and tetanic presynaptic nerve stimulation, 5-hydroxytryptamine always mimicked the slow synaptic response indicating that 5-hydroxytryptamine may function as a slow synaptic mediator in some myenteric neurons. Myenteric neurons identified by intracellular injection of the neuronal marker Neurobiotin TM were found to conform to the morphological classification schemes proposed for myenteric neurons of the guinea-pig and porcine intestine, that is, Dogiel Types I and II and Stach Type IV neurons were present. Simultaneous electrophysiological recording and intracellular staining techniques revealed that a correlation existed between the electrophysiological and morphological properties of myenteric neurons of the rat colon, with electrophysiological classified S/Type 1 neurons having Dogiel Type I morphologies (95/108 neurons; 88%) and electrophysiological classified AH neurons having Dogiel Type II morphologies (87/94 neurons; 93%)...

Animals↗

Histogenesis of the mucosa of the descending colon in mouse fetuses.

The present study clarify intraepithelial events occurring during the formation of intestinal crypts in the descending colon. In early stage, the mucosa is lined with a simple columnar epithelium consisting of undifferentiated cells which are mutually joined by the junctional complex surrounding the intestinal lumen. The epithelium becomes thickened and stratified, and secondary junctional complexes are formed in the abluminal part of the epithelium. An intracellular cavity opens to the focal tight junction of the secondary junctional complex to form an intraepithelial (intercellular) cavity surrounded by the tight junction. The intraepithelial cavity grows by the fusion of intracellular cavities and vesicles as well as by the division of surrounding cells. Intraepithelial cavities fuse with each other and with the main intestinal lumen. This, together with mesenchymal invasion, results in the formation of intestinal crypts lined with a simple columnar epithelium, where various cell types begin to differentiate. These processes seem essentially similar to those occurring in the developing small intestine except that villi, not crypts, are formed in the small intestine. It is suggested that the formation site and elongation of the tight junction provide for the location and fusion of intraepithelial cavities and eventually result in the formation of villi or crypts, alternatively.

Animals↗

Primary malignant fibrous histiocytoma of the descending colon.

We herein present the case of a 50-year-old woman with malignant fibrous histiocytoma arising from the descending colon and localizing in the colonic wall. Malignant fibrous histiocytoma of the large bowel is a very rare tumor. A total of 18 cases, including our case, have been reported in the world medical literature so far and we also reviewed these cases. In our case, combined adjuvant chemotherapy was administered after a complete resection had been performed. No clinical signs of local recurrence or distant metastasis were found at 7 years after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

Epithelial cell kinetics in the descending colon of the rat. I. The effect of ischaemia-induced epithelial cell loss.

Epithelial cell loss was induced in the descending colon of the rat by temporary ischaemia to investigate whether this would lead to an increase in crypt cell proliferation. Shortly after the temporary ischaemia the number of cells per crypt was markedly reduced, and it was shown that the cell loss occurred mainly from the non-proliferating upper half of the crypt. The number of cells per crypt reached control values again after 24-48 h. There was a marked increase in proliferative activity, as reflected by the labelling index after 3HTdR and by the mitotic index, with peak values at 16 and 24 h after ischaemia. After 48 h the proliferative indices were normal again. The increase in crypt cell proliferation was characterized by an increase in the labelling index as well as in the mitotic index per crypt cell position. No enlargement of the proliferative cell compartment in the crypt was observed. It is most likely then that the increase in crypt cell proliferation was brought about by a shortening of the cell cycle, since the growth fraction in the lower half of the crypt approaches 1.0. The possible implications of the present data for the control of colonic cell proliferation and colonic carcinogenesis are discussed.

Animals↗

Do internal iliac arteries contribute to vascularization of the descending colon during abdominal aortic aneurysm surgery? An intraoperative hemodynamic study.

The inferior mesenteric artery (IMA) is the nutrient artery for the descending colon. Colon ischemia after repair of abdominal aortic aneurysm (AAA) can be prevented by routine or elective revascularization of the IMA. In case of occlusion of the IMA, revascularization of the internal iliac artery (IIA) has been recommended but its effectiveness has never been documented. In this study, intraoperative hemodynamic monitoring of the IMA was performed to determine if the IIA contributed significantly to the region supplied by the IMA. From January 1998 to August 1999, a total of 223 patients underwent AAA repair at 11 vascular surgery centers. The IMA was occluded in 113 of these patients (51%). This study involves the other 110 patients (49%) with patent IMA. Study consisted of measuring residual systolic arterial pressure in the IMA (IMAP) immediately after AAA repair. To compensate for blood pressure variations, systolic pressure in the radial artery (RAP) was measured concurrently and the inferior mesenteric index (P) was calculated by dividing IMAP by RAP. Measurements were made before and during cross-clamping of the IIA to obtain two corresponding indexes-i.e., P1 and P2, respectively. Mean P1 and P2 were 0.61 (95% confidence interval, 0.8-0.4) and 0.58 (95% confidence interval, 0.55-0.61), respectively, with p

Aged↗

Actions of the Cl- channel blocker NPPB on absorptive and secretory transport processes of Na+ and Cl- in rat descending colon.

The effects of the Cl- channel blocker, NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), on the transport of Na+ and Cl- in the descending colon of the rat were studied in the Ussing chamber. In control tissue, NPPB administered at the mucosal side of the epithelium increased the short-circuit current (Isc) and inhibited the unidirectional mucosa-to-serosa fluxes of Na+ and Cl-. In HCO3- - or Cl- -free media for in the presence of SITS (4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid), this increase in Isc caused by mucosal NPPB was not observed. The serosal administration of NPPB was without effect. Mucosal NPPB (10(-4) mol l-1) decreased the forskolin-induced increase in Isc by only about 60%. However, the activation of the serosa-to-mucosa flux of Cl- caused by forskolin was inhibited completely. NPPB decreased the mucosa-to-serosa fluxes of Na+ and Cl- reduced additionally by forskolin. Serosal NPPB decreased Isc and FNasm, but had no effect on FNams or FClmas. In HCO3- -free buffer the increase in Isc induced by forskolin was inhibited completely by NPPB. The inhibition of Cl- secretion by NPPB fits well with the capacity of the drug to block Cl- channels. For the inhibition of neutral NaCl absorption two sites of action are discussed: an interaction with the Cl-/HCO3- exchanger or an interference with the extrusion of Cl- through the basolateral membrane.

Animals↗

Sodium pump quantity and turnover in rabbit descending colon at different rates of sodium absorption.

3H-Ouabain binding to isolated epithelia and basolateral membrane vesicles of Na+-transporting epithelial cells of rabbit descending colon was determined to quantify the number of operative Na+-pump sites at different rates of transcellular Na+ transport which was varied over a wide range by chronic dietary Na+ restriction or Na+ loading. Both in intact epithelia and in basolateral membrane vesicles the maximal number of specific ouabain binding sites was higher in preparations from animals transporting Na+ at high rates than in preparations from animals transporting Na+ at low rates. The affinity of ouabain to its binding site and the association and dissociation rate constants were not dependent on the rate of Na+ transport. In intact epithelia the Na+ turnover rate per pump unit was twice as high in tissues with high Na+ transport than in tissues with low Na+ transport. In basolateral membrane vesicles the Na+ turnover rate was considerably higher than in intact epithelia and there was no difference in turnover rate between vesicle preparations obtained from tissues transporting Na+ at high or low rates. Hence, factors within the intact cell appear to control the turnover rate of the Na+-pump.

Animals↗

Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis.

A case of giant inflammatory polyposis associated with a localized inflammatory bowel disease of the descending colon in a 49-year-old man is presented. Lower abdominal distension rapidly appeared without any previous history of gastrointestinal disease. Two months later, he underwent a left hemicolectomy. Postoperative recovery was complete and he remains in good health more than 2 years later. The resected colon showed a giant and bizarre polyposis measuring up to 12 cm in length and 2 cm in height and covering the entire circumference of the colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregularly shaped ulcers, which sometimes extended into muscularis propria. Although longitudinal ulcers or scars, stricture, and a cobble-stone appearance were not observed, transmural inflammation and deep fissures were found in the interpolypoid area. From these findings, this case seems to be more similar to Crohn's disease than other inflammatory bowel diseases.

Colitis↗

Regional differences in the number and type of myenteric neurons in the descending colon of rats.

The purpose of this study was to analyze the neuronal density of the myenteric plexus of the intermediate and antimesocolic regions of the descending colon of rats. Whole-mounts were stained with three different techniques of neuronal evidenciation. Through counts of the number of neurons in an area of 6.64 mm under light microscopy, we found 1,271 +/- 227.54 neurons with Giemsa in the intermediate region and 1,234 +/- 225.92 neurons in the antimesocolic region; with the NADH-diaphorase technique we found 530 +/- 92.97 neurons in the intermediate region and 539 +/- 146.72 neurons in the antimesocolic region; and through the NADPH-diaphorase histochemistry, we found 417 +/- 34.42 neurons in the intermediate region and 547 +/- 84.01 neurons in the antimesocolic region. We conclude that there is a variation in the density of NADPH-diaphorase positive neurons in the intestinal circumference; that the NADH-diaphorase positive neuronal subpopulation represented 42.7% of that stained with Giemsa; and that the NADPH-diaphorase positive neurons represented 37.8% of the whole myenteric population.

Animals↗

[An early cancer of the descending colon, histologically showing a poorly differentiated adenocarcinoma].

Reported is the case of a 71 year-old male with a poorly differentiated adenocarcinoma of the colon that had invaded the submucosal layer. A barium enema had revealed a polyp, 1.5 cm in diameter, in the descending colon, and an endoscopic polypectomy was performed. The resected specimen mainly consisted of an adenoma and a partial, poorly differentiated adenocarcinoma that had massively infiltrated into the submucosal layer. A left hemicolectomy was carried out, and no carcinoma was identified in the resected colon and/or the regional lymph nodes.

Adenocarcinoma↗

Absorption and secretion of potassium by rabbit descending colon.

Measurements of K fluxes under a variety of conditions have provided an internally consistent set of data that demonstrate active absorption and active secretion of K by rabbit descending colon in vitro. The properties of K diffusion across the paracellular pathway are those of a free solution shunt. With Na and Cl present on both sides of short-circuited tissues the two opposing active K transport systems balance each other, so that there is no net K transport. Net K absorption results when the transcellular secretory K flux is inhibited by 1. serosal addition of ouabain, 2. serosal addition of furosemide, or 3. omission of either Na or Cl from the serosal solution. Hence basolateral K uptake appears to be mediated by a furosemide-sensitive Na-Cl-K cotransport system in addition to the Na-K exchange pump. Luminal addition of mersalyl or orthovanadate inhibits active K absorption. The adenosine analogue 5'-N-ethylcarboxamide adenosine and the beta-adrenergic agent isoproterenol, added to the serosal solution, cause net K secretion which is inhibitable by furosemide. The secretory K fluxes, both under stimulated and nonstimulated conditions, are abolished by an opposing electrical gradient, suggesting conductive K exit across the apical cell membrane, whereas K absorption appears to be an electroneutral process.

Absorption↗