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Ions and water in the epithelial cells of rabbit descending colon.

1. Isolated sheets of rabbit descending colon epithelial cells stripped from their underlying muscle coats were incubated in chambers at 37 degrees C with oxygenated media, and their non-inulin space water, sodium, potassium and chloride contents were subsequently determined. 2. With sodium Ringer bathing both surfaces, amiloride, 10(-4) M, decreased non-inulin space sodium content by 76 mmol/kg dry wt. Ouabain, 10(-3) M, caused loss of non-inulin space potassium which was not completely compensated for by uptake of sodium over 30 min incubation. Chloride and water, therefore, decreased. Amiloride, 10(-4) M, inhibited but did not prevent this uptake of sodium after ouabain. 3. Tissues exposed to sodium-free choline Ringer rapidly exchanged non-inulin space sodium for choline and, more slowly, lost potassium, chloride and water. The equilibration of sodium in the non-inulin space when sodium Ringer was restored to the mucosal medium alone was largely amiloride-insensitive. For restoration of non-inulin space potassium to normal levels, sodium was required in the serosal but not the mucosal medium. 4. Neither the absence of glucose nor the absence of chloride from the mucosal medium affected the non-inulin space sodium content when sodium was restored to the mucosal medium bathing sodium-depleted tissues. 5. It is argued that, whereas non-inulin space potassium and water contents are synonymous with their cellular values, only about one third of non-inulin space sodium is cellular when sodium Ringer bathes both surfaces, and the concentration of the sodium within the cellular transport pool approximated 20 mmol/kg H2O, consistent with estimates obtained from other techniques.

Amiloride↗

Inhibitory effects of NPY on ganglionic transmission in myenteric neurones of the guinea-pig descending colon.

Intracellular recordings were made from myenteric neurones of the guinea-pig descending colon. Neuropeptide Y (NPY) and related pancreatic polypeptides were applied by superfusion and the effects upon the amplitude of fast excitatory synaptic potentials (ESPs) and the ratio of paired fast ESPs evoked by stimulation of internodal fibre tracts were noted. NPY produced a concentration-dependent inhibition in fast ESP amplitude in the majority of neurones (17/21) with a calculated IC50 value of 7 nM; in some neurones this inhibition was mediated via the local release of noradrenaline. Peptide YY (PYY) (eight out of 11 neurones; IC50 = 1 nM), NPY(3-36) (three out of three neurones) and [Leu31, Pro34]NPY (four out of five neurones) also decreased the amplitude of fast ESPs. The effects of two or more pancreatic polypeptides or analogues on fast synaptic transmission were compared directly in six neurones; the apparent relative potency of agonists suggested the involvement of Y2-receptors and at least one other Y-receptor type. In the absence of any direct postsynaptic effects of pancreatic polypeptides on the active or passive properties of myenteric neurones, or on their sensitivity to ionophoretically applied acetylcholine, inhibition of fast ganglionic transmission was presumed to be presynaptic in origin. It is concluded that, in addition to their previously described depressant actions on neuro-effector transmission to colonic smooth muscle, pancreatic polypeptides can exert powerful inhibitory effects on myenteric neurones of the descending colon.

Adrenergic alpha-Agonists↗

The efferent mechanisms of reflex hemodynamic responses to distension of the descending colon in anesthetized dogs.

We have recently shown that distension of the descending colon in anesthetized dogs causes reflex increases in heart rate, aortic blood pressure and the maximal rate of rise of left ventricular pressure, involving afferent pathways in the hypogastric nerves. In this study we have examined the efferent mechanisms involved in those responses. The descending colon was distended using Ringer solution at constant pressure in 13 anesthetized dogs. As previously shown, distension of the colon caused an increase in aortic blood pressure, heart rate and the maximal rate of rise of left ventricular pressure. The increase in the aortic blood pressure was abolished by either bretylium tosylate or phentolamine. Propranolol or bretylium tosylate abolished the increases in heart rate when changes in the aortic blood pressure were prevented, and abolished the increases in the maximal rate of rise of left ventricular pressure when the increases in heart rate were also prevented. These results indicate that the reflex increases in heart rate, arterial blood pressure and the maximal rate of rise of left ventricular pressure involved efferent sympathetic pathways.

Animals↗

[A case of advanced descending colon cancer with peritoneal dissemination responding to weekly high-dose l-leucovorin/5-fluorouracil combination therapy].

We report a case in which l-leucovorin/5-fluorouracil (l-LV/5-FU) combination therapy was remarkably effective for non-resectable advanced descending colon cancer with carcinomatous peritonitis. A 65-year-old man complained of severe abdominal distension, abdominal pain and pulmonary failure, and was diagnosed as having ileus due to descending colon cancer. The patient underwent urgent open laparotomy to release the ileus condition on March 5, 2002. During the laparotomy, we established a diagnosis of nonresectable descending colon cancer accompanied by severe peritoneal dissemination and therefore performed only double-barreled transverse colostomy. The postoperative course was very good. Pathological examination of omental dissemination demonstrated moderately differentiated adenocarcinoma and cytology of ascites was class II. The levels of serum CEA and CA19-9 were within the normal ranges. l-LV/5-FU therapy was initiated postoperatively. Seven cycles of this chemotherapy regimen was performed with no apparent side effect during the treatment. There was no postoperative accumulation of carcinomatous ascites. The patient gained 15 kg compared with body weight admission. On abdominal computed tomography (CT), the primary lesion of the colon decreased 98% and there was no ascites found. To date, there has not been any sign of recurrence during the 19 months of follow-up after this therapy, and we are currently discussing closure of the transverse colostomy. This therapy may be useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

Adenocarcinoma↗

Panniculitis of the descending colon caused by enterocolic phlebitis: a case report.

A 73-year-old male was referred to our hospital for abdominal pain, diarrhea and general fatigue lasting for 3 weeks. Physical examination of the abdomen revealed a firm mass in the left abdominal region. Computed tomography revealed a mass around the descending colon. Colonoscopy and barium enema revealed poor extensibility of the lumen with edematous mucosa, and narrowing of the descending colon with rugged mucosal surface. Because of the clinical symptoms and findings, the patient was diagnosed clinically as suffering from panniculitis of the descending colon. He underwent the left hemi-colectomy with side-to-side colo-colostomy after making of a loop ileostomy. Histological analysis of the resected colon showed an infiltration of inflammatory cells, predominantly lymphocytes, into veins and venules of the submucosa, muscularis propria and fat tissue of the colonic mesentery, with an involvement of all layers of the vessel wall. Arteries were escaped from inflammatory changes. The histopathological diagnosis of enterocolic phlebitis and venulitis was made because of these findings.

Aged↗

Electrical stimulation to induce propulsive contractions in the porcine descending colon.

Electrical stimulation of the colon can improve transit in slow-transit constipation, or enable controlled emptying in colostomy patients. Preliminary studies showed that sequential stimulation of consecutive colon segments induced serial contractions resulting in colonic propulsion. This study was performed to optimize the stimulation parameters. The electrodes were inserted under the serosa of the descending colon of pigs. Charge-balanced rectangular pulses at 10 Hz were delivered in consecutive sessions. Electrically evoked contractions (ECs) were monitored using impedance planimetry and manometry. The luminal pressure and cross-sectional area (CSA), the latency and velocity of CSA decrease, and the wall tension were compared for ECs induced using 3 ms pulses of 9, 12, 15, and 30 mA. When using 15 mA, ECs induced by 0.03, 0.3, and 3 ms long pulses were compared. A current increase from 9 to 30 mA induced a significant increase in the pressure generated by contraction. The increase in pulse duration from 0.03 to 3 ms resulted in shorter latency, faster contraction, higher pressure, and higher wall tension. It is concluded that, at a frequency of 10 Hz, the best combination of current and pulse duration to elicit propulsive contractions in the descending colon of pigs is 15 mA and 3 ms.

Animals↗

[Spontaneous rupture of a pancreatic pseudocyst into the descending colon].

A 50-year-old male with nausea and upper abdominal pain was hospitalised. After five days, lower gastrointestinal bleeding occurred. Computed tomography (CT) revealed a pancreatic pseudocyst. Coloscopic biopsy indicated fistulisation of a pancreatic pseudocyst into the descending colon. The patient was successfully treated nonoperatively, using only antibiotics.

Abdominal Pain↗

Neuropeptide Y hyperpolarizes submucosal neurons of the guinea-pig descending colon.

Effects of neuropeptide Y (NPY) on submucosal neurons of the guinea-pig descending colon were investigated electrophysiologically by means of intracellular electrophysiological recordings. NPY (100 nM) induced a marked and prolonged hyperpolarization, accompanied by a decrease in input resistance in most (90%) neurons. This NPY-induced hyperpolarization was diminished and augmented by membrane hyperpolarization and depolarization, respectively. The NPY-hyperpolarization was not affected by exposure to either calcium-free solutions or the alpha2-adrenoceptor antagonist, idazoxan (1 microM). When more than one peptide was applied to a neuron, NPY, PYY and Pro34-NPY were equipotent, whilst NPY13-36 was less potent. It was concluded that NPY hyperpolarized submucosal neurons of the guinea-pig descending colon, possibly via a direct action on postsynaptic Y1-receptor and increasing potassium conductance.

Animals↗

Haemodynamic effects of distension of the descending colon in anaesthetized dogs.

1. This study was undertaken to determine whether distension of the descending colon in anaesthetized dogs reflexly affects the heart rate, arterial blood pressure or the left ventricular inotropic state. 2. Experiments were performed on twenty-six dogs, which were anaesthetized with sodium pentobarbitone and artificially ventilated. A segment of the distal descending colon was isolated and was distended with warm Ringer solution at a steady intraluminal pressure. 3. In each animal, distension of the colon caused an increase in heart rate and aortic blood pressure. The response of an increase in heart rate was augmented by preventing changes in aortic blood pressure, and was graded in seven dogs by step increments in the distending pressure. In the same animals, distension of the colon always caused a small increase in left ventricular (dP/dt)max at constant heart rate and aortic blood pressure. 4. In four of the twenty-six dogs, cutting the pelvic nerves did not abolish the observed responses to the distension. In seven of the twenty-six dogs, which included the four animals with sectioned pelvic nerves, cutting the hypogastric nerves completely abolished all the observed responses. 5. In thirteen of the twenty-six dogs, propranolol or bretylium tosylate completely abolished the reflex increases in heart rate and left ventricular (dP/dt)max, and phentolamine or bretylium tosylate abolished the reflex increase in aortic blood pressure. 6. These results showed that distension of the colon reflexly increased the heart rate, arterial blood pressure and left ventricular inotropic state. These reflex responses were mediated by sympathetic effects and their afferent limb involved the hypogastric nerves.

Animals↗

Brain activity during distention of the descending colon in humans.

Brain-gut interaction is considered to be a major factor in the pathophysiology of irritable bowel syndrome. However, only limited information has been provided on the influence of gastrointestinal tract stimulation on the brain. Our aim in this study was to determine the specific regions of the brain that are responsible for visceral perception and emotion provoked by distention of the descending colon in humans. Fifteen healthy males aged 22 +/- 1 participated in this study. Using a colonoscope, a balloon was inserted into the descending colon of each subject. After sham stimulation, the colon was randomly stimulated with bag pressures of 20 and 40 mmHg, and regional cerebral blood flow was measured by [(15)O] positron emission tomography. The subjects were asked to report visceral perception and emotion using an ordinate scale of 0-10. Colonic distention pressure dependently induced visceral perception and emotion, which significantly correlated with activation of specific regions of the brain including the prefrontal, anterior cingulate, parietal cortices, insula, pons, and the cerebellum. In conclusion, distention of the descending colon induces visceral perception and emotion. These changes significantly correlate with activation of specific regions in the brain including the limbic system and the association cortex, especially the prefrontal cortex.

Adult↗

Splenodiaphragmatic interposition of the descending colon.

We present a variation named splenodiaphragmatic or retrosplenic interposition of the colon in three patients aged 6, 70, and 71 years who suffered from different symptoms. The cases were found in 1,000 thoracoabdominal CT scans examined at the radiology clinic between 1999 and 2001. The upper part of descending colon was seen to be between the spleen and the left kidney on abdominal CT scans with contrast enema in the patient aged 71 years. In a 6 year-old child, part of the left colic flexure in the intestinal gas patterns was located between the left kidney and spleen, extending up to the diaphragm in the left hypochondrium on radiological examinations. The left colic flexure and the beginning of the descending colon were imaged on CT behind the spleen at the level of the 11th thoracic vertebra in the third patient aged 70 years. Hepatodiaphragmatic interposition of the colon has been reported previously in many patients; however, no detailed reports are available dealing with the interposition of the descending colon between the diaphragm and spleen. Three cases with retrosplenic colon variation were investigated in detail in the present study. The significance of retrosplenic colon is discussed. It is concluded that the identification of this anatomical variation could avoid unnecessary colon perforation during percutaneous nephrostomy, splenostomy, biopsy, or splenectomy.

Aged↗

Cellular-mediated and diffusive magnesium transport across the descending colon of the rat.

Concentration and voltage dependence of unidirectional magnesium fluxes across the rat descending colon were measured in a modified Ussing-chamber. Mucosa to serosa (ms) magnesium flux exhibits a saturable component, whereas serosa to mucosa (sm) flux is linearly related to the magnesium concentration from 0.125 to 8 mmol/L. At all the concentrations used, ms magnesium transport is higher than the flux in the opposite direction, resulting in net magnesium absorption. Only ms magnesium transport has a voltage-independent, i.e., cellular-mediated component. Magnesium flux from serosa to mucosa, however, is totally voltage-dependent, i.e., purely diffusive and probably constrained to the paracellular pathway. The cellular-mediated fraction of ms magnesium transport is comparable to that found for calcium. Calcium (5 mmol/L) has no influence on ms flux or on the magnesium flux in the opposite direction. Magnesium (5 mmol/L) has no influence on the sm calcium flux but abolishes calcium absorption by decreasing ms calcium flux. The voltage clamp experiments reveal that magnesium has no influence on the cellular-mediated ms calcium transport but exclusively decreases diffusive calcium flux in this direction. Pretreatment with 1 alpha,25-dihydroxyvitamin D3 (250 ng/kg s.c. daily given for 4 days) has no effect on ms magnesium flux but it remarkably stimulates ms calcium transport. These findings suggest that both earth alkaline ions in the descending colon are transported by separate cellular-mediated mechanisms. On the other hand, the similarity of the kinetic parameters as well as the similarity of the voltage-independent ms fluxes would support the assumption that both ions are absorbed by the same mechanism. Hence, the question of whether both ions are absorbed by the same or by distinct transport processes cannot be answered by the present experiments. Diffusive movement across the paracellular route plays an important role in net transport of both ions. Diffusive magnesium flux is equal in both directions. In contrast, for calcium an asymmetry in the paracellular fluxes with a prevalence of the diffusive sm flux over the diffusive fraction of the flux from mucosa to serosa has been reported. The different behavior with respect to the paracellular movement can be explained by the radius of the hydrated magnesium ion, which is smaller than calcium with its hydration shells.

Animals↗

Pericryptal myofibroblast growth in rat descending colon induced by low-sodium diets is mediated by aldosterone and not by angiotensin II.

Pericryptal myofibroblast growth in descending colonic crypts correlates with the activation of the renin-angiotensin-aldosterone system. Earlier work showed that during the transition from a high-Na(+) (HS) to low-Na(+) (LS) diet there are changes in the colonic crypt wall and pericryptal sheath. As LS diet increases both aldosterone and angiotensin II, the aim here was to determine their individual contributions to the trophic changes in colonic crypts. Experiments were conducted on control and adrenalectomized Sprague-Dawley rats fed an HS diet and then switched to LS diet for 3 days and supplemented with aldosterone or angiotensin II. The actions of the angiotensin-converting enzyme inhibitor captopril, the angiotensin receptor antagonist losartan and the aldosterone antagonist spironolactone on extracellular matrix proteins, claudin 4 and E-cadherin myofibroblast proteins, alpha-smooth muscle actin (alpha-SMA) and OB-cadherin (cadherin 11), angiotensin type 1 and TGFbetar1 membrane receptors were determined by immunolocalization in fixed distal colonic mucosa. The LS diet or aldosterone supplementation following ADX in HS or LS increased extracellular matrix, membrane receptors and myofibroblast proteins, but angiotensin alone had no trophic effect on alpha-SMA. These results show that aldosterone stimulates myofibroblast growth in the distal colon independently of dietary Na(+) intake and of angiotensin levels. This stimulus could be a genomic response or secondary to stretch of the pericryptal sheath myofibroblasts accompanying enhanced rates of crypt fluid absorption.

Adaptation, Physiological↗

In vivo fluorescence measurement of Na(+) concentration in the pericryptal space of mouse descending colon.

A method involving surgical exposure of the colonic mucosa, fluorescent dye addition, and confocal microscopy has been developed for monitoring colonic crypt function in vivo in mice. Na(+) concentration in the extracellular pericryptal space of descending colon was measured using a low-affinity Na(+)-sensitive fluorescent indicator consisting of an Na(+)-sensitive chromophore (sodium red) and an Na(+)-insensitive chromophore (Bodipy-fl) immobilized on 200-nm-diameter polystyrene beads. The Na(+) indicator beads accumulated in the pericryptal spaces surrounding the colonic crypts after a 1-h exposure of the colonic luminal surface to the bead suspension. Na(+) concentration ([Na(+)]) in the pericryptal space was 491 +/- 62 mM (n = 4). After a 70-min exposure to amiloride (0.25 mM), pericryptal [Na(+)] was reduced to 152 +/- 21 mM. Blockage of the crypt lumen with mineral oil droplets reduced pericryptal [Na(+)] to 204 +/- 44 mM. Exposure of the colonic mucosa to FITC-dextran (4.5 kDa) led to rapid accumulation of the dye into the crypt lumen with a half time of 19.8 +/- 1.0 s, which was increased to 77.9 +/- 6.0 s after amiloride treatment. These results establish an in vivo fluorescence method to measure colonic crypt function and provide direct evidence for accumulation of a hypertonic absorbate in the pericryptal space of descending colon. The pericryptal space represents the first example of a hypertonic extracellular compartment in mammals that is not created by a countercurrent amplification mechanism.

Amiloride↗

Food deprivation increases apoptotic cell counts induced by 1,2-dimethylhydrazine in rat descending colonic and rectal crypts.

The frequency of apoptosis after treatment with 1,2-dimethylhydrazine (DMH) was counted in the descending colonic and rectal crypts of food-deprived and fed rats. Food-deprived or fed rats were subcutaneously injected with DMH (100 mg/kg body weight). Six hours after the injection, apoptotic cells were observed in crypt regions by light microscopy. The incidence of DMH-induced apoptosis in food-deprived rats was significantly higher than in fed rats. The incidence appeared to be higher in descending colon than in rectum. PAS staining revealed that DMH treatment lowered mucin secretion in crypts, which was substantially lowered by food deprivation. The effect of food deprivation on apoptosis induced by DMH may be due to the decrease in mucus barrier against DMH.

1,2-Dimethylhydrazine↗

The dehydrating function of the descending colon in relationship to crypt function.

Very high pressure is required to generate hard faeces approximately 5-10 atmospheres. This is much more than can be supplied by the mechanical force from the muscular wall of the colon. Osmotic pressure (at least 200 mOsm) can generate the necessary suction forces required to consolidate faeces. The colon has a hypertonic absorbate (net above plasma approximately 500 mOsm) in vivo. Fluorescence imaging of perifused rat descending colonic mucosa shows high steady state Na+ concentrations (600 mM) in the intercryptal extracellular space and low [Na+] present in the crypt lumen. This [Na+] distribution generates an osmotic pressure gradient across the crypt luminal wall resulting in a fluid inflow into the crypt lumen. Direct observation using confocal fluorescence microscopy of FITC dextran (mol. wt. 10,000) shows that there is concentration polarisation of the dextran in the upper 30% of the crypt lumen. The time course and steady state distribution of concentration polarisation of fluorescent dyes within the crypt lumen permit an estimation of the fluid convection rate along the length of the crypt lumen. This is sufficient to account for the majority of fluid absorption by the colon. Observation of the suction force on agarose gels by rat descending colon in vivo shows that the colon generates up to 4,000 cm H2O suction pressure on the stiff gels, this is accompanied by a hypertonic absorbate from the gels of 800 mOsm. Disruption of the colonic mucosa by bile salts reduces the suction pressure to about 40 cm H2O.

Animals↗