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PubMed1994

[New findings on the mechanism and regulation of intestinal calcium transport].

Only in the duodenum and in the colon calcium is absorbed by a cellular 1,25 alpha-Vitamin D3-dependent transport mechanism. Calcium absorption is highest in the proximal large intestine, about ten times higher than in the duodenum or in the descending colon. 1,25 alpha-Vitamin D3 stimulates calcium transport by genomic (slow effect: synthesis of cytosolic calcium binding protein CabP and basolateral Ca-ATPase) and non-genomic action (rapid effect: transcaltachyia, liponomic effect at the brush border membrane). CabP-dependent translocation across the cytosol is thought to be rate limiting step of cellular calcium transport. However, only about 50% of calcium absorption is cellular mediated but the same amount of calcium convectively is absorbed by transepithelial water flow across the paracellular pathway (solvent drag effect). 1,25 alpha-Vitamin D3 not only activates cellular calcium absorption but also increases paracellular permeability for calcium by an unknown mechanism. However, essential steps in the cascade from the interaction of 1,25 alpha-Vitamin D3 with the specific receptor over the regulation of the synthesis of calcium binding and transporting proteins to the induction of cellular calcium transport are not as yet clearly understood. The exact feedback mechanism of synchronized calcium transport across the distinct subcellular compartments seems also to be resolved. Cellular calcium transport is not found in the jejunum or in the ileum, what can be explained by the absence of specific 1,25 alpha-Vitamin D3-dependent carrier systems in these segments. On the other hand calcium is secreted across the jejunum and ileum by an anomalous solvent drag effect. Hence, intestinal calcium metabolism seems to underlie an eneteroenteral circuit: 1,25 alpha-Vitamin D3-controlled cellular calcium absorption across the duodenum is followed by paracellular calcium secretion across the jejunum and ileum. The carrier in the proximal colon which works at the optimal level already under normal nutritional condition could be of physiological importance for the reclamation of unabsorbed dietary calcium and for the reabsorption of calcium that is secreted across the distal small intestine. Under certain pathophysiological conditions, i.e. malabsorption in proximal segments or malnutrition, calcium in addition may be conserved by the 1,25 alpha-Vitamin D3-sensitive carrier in the descending colon.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

Histiocytic ulcerative colitis in a boxer. A case report.

A case of canine histiocytic ulcerative colitis, a disease of boxers, is here described. It appears that this disease has not been previously reported in Scandinavia. The diagnosis was established at necropsy of a 5-month-old boxer, which had shown bloody diarrhoea since the age of four weeks. Treatment with antibiotics had only given a temporary remission of the condition. Macroscopical findings included thickening of the wall of the descending colon and rectum, multiple ulcers in the rectocolonic mucosa and marked enlargement of the colonic lymph nodes. Microscopically the lesions were characterized by large accumulations of PAS-positive histiocytes, mixed with cells of the plasma cell type, in the mucosa and submucosa of the rectum and descending colon and in the colonic lymph nodes. The importance of using proctocolonoscopy and colon biopsy for the clinical diagnosis of this condition is stressed.

Animals↗
PubMed1994

Serotonergic mediation of postprandial colonic tonic and phasic responses in humans.

This study examined the hypothesis that 5HT3 mechanisms mediate the postprandial gastrocolonic response in humans. Fasting and postprandial colonic tone and motility were studied in 12 healthy volunteers and the effects of a selective 5HT3 antagonist, ondansetron assessed in a double blind, randomised, placebo controlled fashion. A manometry barostat assembly was positioned in the transverse or descending colon to quantitate contractile activity fasting, after drug infusion and postprandially after a 1000 kcal meal. Fasting colonic tone and motility indices were similar in the placebo and ondansetron groups; ondansetron did not affect fasting motility. The placebo group showed a significant reduction in barostat balloon volume (signifying increased tone) from 232 ml (median, interquartile range (IQR) 179-261) during fasting to 181 ml (median, IQR 128-208) (postprandially) (p = 0.02). In contrast, the ondansetron group did not have a tonic colonic response (median 248 ml (IQR 199-300) fasting to median, 226 ml (IQR 185-290) postprandially) after the meal. Phasic volume events measured by the barostat increased postprandially in both groups. Postprandial motor activity measured by manometry increased significantly in the placebo group, but not in the ondansetron group. In conclusion, a 5HT3 mechanism participates in the physiological contractile responses in the human transverse and descending colon after ingestion of a high energy meal.

Adult↗
PubMedDate not supplied

Study of the effect of colonic mass movements on the rectosigmoid junction with evidence of colo-rectosigmoid junction reflex.

Mass movements of the left-sided colon bring the colonic material contained in it to the sigmoid colon. The cause why the colonic contents do not pass directly to the rectum but stop short of the rectosigmoid junction (RSJ) was studied. The study comprised 10 healthy volunteers (mean age 39.2 +/- 10.2 years; 8 men, 2 women). A condomended tube was introduced into the descending colon (DC) per anum. The pressure response of the DC, sigmoid colon (SC), and RSJ to condom inflation with carbon dioxide (CO2) in increments of 10 ml was recorded by means of a three-channel microtip catheter. The responses were registered upon inflation of the upper, middle, and lower third of the DC. The test was repeated after individual anesthetization of the descending colon and the RSJ on separate days. Colonic distension with 10 and 20 ml CO2 produced no significant pressure changes in the DC, SC, and RSJ (p > .05); 30 ml distension effected a pressure rise in both the DC (p < .01) and RSJ (p < .05), but no change in the SC pressure (p > .05); and 40, 50, and 60 ml distension produced pressure changes similar to those obtained with 30 ml distension. The RSJ pressure responded to distension of the saline-injected but not of the anesthetized DC. Thus, the RSJ response to colonic distension affirms the hypothesis of the possible involvement of a reflex, which we term colo-RSJ reflex. This reflex seems to regulate the passage of stools from the colon to the rectum. Further studies are required to investigate its role in the diagnosis of defecation disorders.

Adult↗
PubMed1982

Fecal blood loss in patients with colonic polyps: a comparison of measurements with 51chromium-labeled erythrocytes and with the Haemoccult test.

The quantitative determinations of fecal daily blood loss after intravenous administration of 51Cr-labeled erythrocytes in 44 patients with colonic polyps and in 11 controls were compared with the results of the daily performed Haemoccult test without dietary restrictions. A total of 642 stool specimens was analyzed for 51Cr loss and the Haemoccult test. The mean fecal daily blood loss in the 34 patients with adenomatous polyps of the descending colon and rectosigmoid was 1.36 +/- 0.14 ml/day (mean +/- SEM), in the 10 patients with polyps of the ascending and transverse colon it was 1.28 +/- 0.31 ml/day, and in the 11 controls 0.62 +/- 0.07 ml/day. There was no positive Haemoccult test in the controls. In fecal specimens from patients with polyps in the descending colon and rectosigmoid containing 2.0-3.99 ml blood/day, the Haemoccult-test was positive in 86%. Fecal specimens from patients with polyps in the ascending colon and transverse colon containing equal blood loss yielded a positive Haemoccult test result in 26%. Thus, the positivity of the Haemoccult test is determined by the fecal daily blood loss and the anatomic location of colonic bleeding sites.

Chromium Radioisotopes↗
PubMed2001

Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families.

Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifetime risk in gene carriers for synchronous and for metachronous colorectal cancer and endometrial cancer in women, prophylactic and extended surgery are considered as options for gene carriers. A 54-year-old patient with a history of metachronous rectal cancer and a family history fulfilling the Amsterdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histological examination of the specimen showed three synchronous colon carcinomas. The 31-year-old son carrying the pathogenic mutation refused to be included in the HNPCC surveillance program. One year later he presented with symptoms of bowel obstruction, and a carcinoma of the descending colon was diagnosed. Intraoperatively, in addition to the colon cancer, a small bowel cancer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented with synchronous cancer of the ascending colon and the lower rectum at the age of 49 years. Proctocolectomy and prophylactic hysterectomy were performed, which revealed an additional colon cancer and endometrial cancer. We discuss approaches for individual decision making for surgery in HNPCC patients. Is a subtotal colectomy indicated in the case of first colon cancer in HNPCC patients, or if the first tumor occurs in the lower rectum, should a proctocolectomy or a restorative proctocolectomy be considered? The aim of prospective clinical studies should be to assess acceptability, survival rates, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophylactic surgery.

Adult↗
PubMed1995

Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis.

BACKGROUND: Rectal foam enemas provide for drug delivery to the distal colon for treatment of left sided ulcerative colitis. However, currently available formulations contain chlorofluorocarbons which are due to be phased out in the near future. The objective of this study was therefore to determine the degree of dispersion of a newly developed non-chlorofluorocarbon rectal foam preparation in ulcerative colitis patients. METHODS: This was an open label non-controlled study of a single administration of a mesalazine foam enema (two actuations containing 2 g of mesalazine in approximately 120 mL foam) in 10 patients with quiescent ulcerative colitis. Spreading of the 99mTc-labelled foam enema was assessed over a 4-h period by the non-invasive technique of gamma scintigraphy. RESULTS: All patients retained the enema for the full 4-h imaging period. In nine out of the 10 patients, the enema was observed to spread as far as the descending colon and on average 23% of the dose was present in the descending colon at 4 h post-dose. CONCLUSIONS: The extent of spreading observed in the study supports the use of the formulation in the treatment of left sided ulcerative colitis.

Aminosalicylic Acids↗
PubMed1968

Factors influencing the electrical potential across the mucosa of rat colon.

1. An investigation has been carried out into various factors which influence the transmucosal potential difference (p.d.) of rat colon in vivo when the p.d. is either high (> 30 mV) or low (< 20 mV).2. The p.d. was uninfluenced by short duration anaesthesia with ether or pentobarbitone. When anaesthesia was prolonged for several hours, p.d. rose steadily. The gradient of p.d. along the descending colon which developed and its elimination by adrenalectomy suggested that the rise was due to increased secretion of adrenal steroids.3. P.d. was increased by Na depletion after a delay of about 18 hr and fell again following Na repletion with a similar time delay. A characteristic gradient of p.d. along the descending colon was seen.4. Both haemorrhage and anoxia caused a rapid fall of p.d. P.d. was restored rapidly to its previous level when anoxia was corrected.5. Vasopressin (I.V.) in low dose was without effect; in high dose it caused a transient fall of p.d. associated with intense vasoconstriction of gut blood vessels.6. The following factors studied were without effect on p.d.: presence of glucose within the lumen; considerable osmotic gradients across the mucosa; variation of luminal pH over the range 5.2-9.8; intravenous administration of acetazolamide, chlorothiazide, frusemide, triamterene, ethacrynic acid or ouabain. Ouabain in the luminal solution also had no effect in all but two rats in which a small fall of p.d. was seen.7. 2,4-dinitrophenol, 10(-2)M, in the lumen caused a small fall of p.d. only if the p.d. was high.8. Experiments were done to determine the effect on p.d. of altering the ionic composition of the luminal solution. When the p.d. was low (< 20 mV) alteration of [Na], [K] or [Cl] produced small absolute changes of the p.d., all of comparable magnitude. The changes could be interpreted as due to diffusion potentials resulting from the ionic gradients across the mucosa. When the p.d. was high (> 30 mV), it showed a striking dependence on the luminal [Na] only, consistent with the presence of a large p.d. due to active Na transport.

Acetazolamide↗
PubMed1997

Higher frequency of aberrant crypt foci in rapid than slow acetylator inbred rats administered the colon carcinogen 3,2'-dimethyl-4-aminobiphenyl.

Humans and other mammals such as rats exhibit a genetic polymorphism in acetyltransferase (NAT2) capacity, yielding rapid and slow acetylator phenotypes. The rapid acetylator phenotype has been associated with increased incidence of human colorectal cancer in some, but not all, epidemiological studies. In order to investigate this possible association, a rapid (F-344) and slow (WKY) acetylator inbred rat model was utilized to investigate the role of the acetylator genotype (NAT2) in the formation of aberrant crypt foci (ACF) following administration of colon carcinogens. Age-matched (retired breeder) female rapid and slow acetylator inbred rats received two weekly injections (50 or 100 mg/kg, sc) of 3,2'-dimethyl-4-aminobiphenyl (DMABP) or a single 50 mg/kg, sc, injection of 1,2-dimethyl-hydrazine (DMH). The rats were euthanized at 10 weeks and ACF were evaluated in the cecum, ascending, transverse, and descending colon, and rectum. ACF were observed in the colon and rectum, but not the cecum of rapid and slow acetylator inbred rats administered DMABP or DMH. ACF were more concentrated in the descending colon. ACF frequencies were significantly higher in colons of rapid than slow acetylator inbred rats administered DMABP, a colon carcinogen which is activated via O-acetylation catalyzed by polymorphic acetyltransferase (NAT2). At 50 mg/kg, ACF frequency in the distal colon was 2.29 +/- 0.57 in rapid acetylators versus 0.38 +/- 0.18 in slow acetylators. At 100 mg/kg, ACF frequency was 4.11 +/- 1.06 in rapid versus 1.57 +/- 0.48 in slow acetylators. ACF frequency did not differ significantly between rapid and slow acetylator inbred rats administered DMH, a colon carcinogen which is not metabolized by polymorphic acetyltransferase. The two inbred rat strains did not differ in hepatic microsomal phenacetin deethylase activity, which is a marker for CYP1A2 activity important for the activation of aromatic amines. These results support the hypothesis that rapid acetylator (NAT2) genotype is a risk factor in aromatic amine-induced colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1988

Routine double contrast barium enema and fiberoptic colonoscopy in the diagnosis of colorectal carcinoma.

The diagnostic efficacy of routine double-contrast barium enema and fiberoptic coloscopy for detection of cancer was retrospectively studied in 303 patients consecutively operated for colorectal adenocarcinoma in a 52-month period from January 1980. Double-contrast barium enema was performed in 180 patients with 184 carcinomas, 157 (85%) of which were revealed by this examination. The detection rate of carcinoma according to site was 89% between cecum and descending colon, 92% in sigmoid colon and 71% in rectum. Fiberoptic colonoscopy was done in 176 patients with 181 carcinomas, 163 (90%) of which were detected by the endoscopical examination. The detection rate of carcinoma according to site was 86% between cecum and descending colon, 90% in sigmoid colon and 95% in rectum. The two methods were equally effective in detecting carcinoma of the colon. Colonoscopy was superior to barium enema in detection of rectal carcinoma.

Adenocarcinoma↗
PubMed2000

Deficiency of the intestinal growth factor, glucagon-like peptide 2, in the colon of SCID mice with inflammatory bowel disease induced by transplantation of CD4+ T cells.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cells of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestinal mucosal growth. Our objective was to study the content of GLP-2 in the large intestine in a murine model of T-cell-induced inflammatory bowel disease. METHODS: Inflammation was induced by adoptive transfer of CD4+ blast T cells from BALB/c mice to SCID mice. The amount of GLP-2 (1-33) was measured with a specific, NH2-terminally directed radioimmunoassay in tissue extracts from the large intestine of transplanted mice developing colitis and from BALB/c and SCID control mice. RESULTS: In the middle and descending colon segments showing the most severe signs of inflammatory lesions in the CD4+ T-cell-transplanted mice, the amount of GLP-2 was significantly lower than in similar colon segments in both untransplanted SCID mice and normal BALB/c mice (P = 0.0013 and 0.0033). In the descending colon the amount of GLP-2 was 6.7 +/- 1.0 pmol/g protein in the CD4+ transplanted mice compared with 68.4 +/- 20.3 and 42.7 +/- 4.3 in the two groups of control mice. Similar findings were made with regard to the contents of the two other proglucagon-derived intestinal peptides, glicentin and GLP-1. CONCLUSION: The amount of GLP-2 is markedly reduced in the colon of mice with a T-cell-induced inflammatory bowel disease histopathologically resembling both Crohn disease and ulcerative colitis. This observation may provide a pathophysiologic rationale for administration of GLP-2 as a trophic factor in inflammatory bowel disease.

Animals↗
PubMed1998

Enterocutaneous fistula: a complication of posterior iliac bone graft harvesting not previously described.

A case of enterocutaneous fistula at the donor site is presented. A patient underwent posterior C5-C6 wire fusion with autologous bone graft taken from the posterior superior iliac crest for degenerative C5-C6 spondylolisthesis. The tip of the osteotome slipped anteriorly during the procurement but neither neurovascular nor peritoneal injury were observed. Spillage of formed faecal material was observed from the donor site on the 12th postoperative day. Fistulogram showed an enterocutaneous fistula to descending colon. The fistula closed spontaneously in a week. Enterocutaneous fistula after bone harvesting has never been reported in the literature as far as we know. Congenital malformations and acquired causes may create a vulnerable peritoneal area. Small bowel or descending colon may show a close relationship or even an adhesion to peritoneum in the presence of local peritonitis. A small lesion in this area may play a role in the occurrence of a fistula, and a low flow pseudofistulous tract may appear. The thermal injury and possible ischaemic necrosis due to cauterisation may be predisposing factors in the aetiology of this kind of fistula. The lack of foreign material and spontaneous closure were against an infectious origin. The aims of this report are to present and analyse the reasons of this complication, not previously described.

Aged↗
PubMed1975

A further investigation into the energy dependence of angiotensin II-induced contractions of isolated smooth muscle preparations.

1 The energy dependence of angiotensin and acetylcholine-induced contractions of rat descending colon and uterus was investigated. 2 Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen. 3 The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4-dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself. 4 The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4-dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis. 5 It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.

Angiotensin II↗
PubMed1995

Effects of long-term treatment with anthranoids and sodium picosulphate on the contents of vasoactive intestinal polypeptide, somatostatin and substance P in the rat colon.

OBJECTIVE: To examine the effects of chronic treatment and a single high-dose application of anthranoids and sodium picosulphate on the neuropeptide content of the rat colon. DESIGN AND METHODS: Over a 6-month period, eight groups of rats were each given one of the following: sennosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/day, respectively), in high daily doses (40 and 10 mg/kg/day, respectively), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectively); high daily doses of danthron (500 mg/kg/day); and vehicle (tragacanth 0.5%) only. Four further groups of rats each received a single dose of vehicle or a high dose of one of the three laxatives. All rats were killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis externa. Vasoactive intestinal polypeptide (VIP), somatostatin, and substance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoassays. RESULTS: After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there was a significant reduction in mucosal levels of VIP and somatostatin and in submucosal levels of somatostatin of both colonic segments, as well as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate had no effect. CONCLUSIONS: Chronic treatment with anthranoids in high doses, but not with sodium picosulphate, reduces VIP and somatostatin levels in the rat colon. This may represent damage to the enteric nervous tissue or a pharmacological effect of the anthranoids, causing decreased synthesis or increased breakdown of these peptides.

Animals↗
PubMed1999

Regional differences in rat large intestinal crypt function in relation to dehydrating capacity in vivo.

1. Rat descending colon absorbed fluid against a large hydraulic resistance, imposed by 10 % agarose (w/v) gel plugs inserted in the lumen, by raising the tonicity of the absorbate from the gel to 880 +/- 54 mosmol kg-1; the tonicity of the absorbate from 2.5 % gels was 352 +/- 38 mosmol kg-1. The hypertonic absorbate generated an osmotic pressure which created a fluid tension in the crypt lumen. This was monitored as a suction tension in colonic luminal gels of 45.3 +/- 3 cmH2O with 2.5 % gels and 725 +/- 145 cmH2O with 10 % gels. The caecum was unable to absorb fluid against a significant hydraulic resistance. 2. Fluorescein isothiocyanate-labelled dextran (FITC dextran; molecular mass 10000 Da) accumulated within descending colonic crypt lumens by concentration polarization. Maximal accumulation at a depth of 20-40 micrometer below the mucosal surface was 5.68 +/- 0.2-fold above control levels. Caecal crypts accumulated dextran to a maximum of 1.8 +/- 0.17-fold above control levels. 3. The relationship between crypt luminal tension and suction tension of the distal colon was also demonstrated using paraffin, which occluded the crypt lumens with microscopic droplets and completely inhibited fluid absorption from high resistance luminal gels. 4. Reduction in dietary Na+ intake raised plasma aldosterone and the capacity of the distal colon to dehydrate against a high luminal hydraulic resistance. The caecum did not respond in this way to varied Na+ intake.

Animals↗
PubMed1998

Effect of bowel preparation and a fiber-free liquid diet on expression of transforming growth factor and procollagen in colonic tissue preoperatively and postoperatively.

PURPOSE: Dehiscence of colonic anastomoses is prevalent and potentially fatal. In an attempt to reduce the likelihood of anastomotic dehiscence, the colon is cleansed before surgery and fiber-free diets are prescribed postoperatively. However, fiber-free diets induce colonic atrophy and impair healing. This study was designed to investigate the effect of bowel preparation and postoperative fiber-free diet on the local gene expression of transforming growth factor-beta 1 and procollagen type I. METHODS: Four Sprague-Dawley rats underwent bowel preparation with a fiber-free liquid diet and polyethylene glycol in a balanced electrolyte solution for two days (fiber-free preoperative diet group), whereas four rats received standard chow with fiber (preoperative diet with fiber group). On the third day tissue was obtained from the descending colon of each rat to assess the effect of bowel preparation. Forty additional rats had their bowels prepared and underwent transection of the descending colon and anastomosis. These rats were then randomly assigned to continue on the liquid diet (fiber-free postoperative diet group) or rat chow (postoperative diet with fiber group). On postoperative days 3, 5, 6, 7, and 14, colonic tissue was obtained from the anastomosis and analyzed with the use of semiquantitative reverse transcriptase-polymerase chain reaction to examine the relative expression of transforming growth factor-beta 1 and procollagen type I genes normalized to that of a constitutive gene. RESULTS: There was a decrease in the expression of the transforming growth factor-beta 1 and the procollagen type I genes in the fiber-free preoperative diet group compared with the preoperative diet with fiber group; however, this difference only reached statistical significance for procollagen type I. Postoperatively, significant increases in the expression of the transforming growth factor-beta 1 and procollagen type I genes over baseline levels were observed around postoperative day 7 in both groups, which temporally correlates with active phases of collagen deposition in the wounded colon. Expression of the procollagen type I gene, however, was significantly decreased at this time in the fiber-free postoperative diet group compared with the postoperative diet with fiber group. CONCLUSION: Although necessary to reduce septic complications, preoperative bowel preparation has a detrimental effect on the expression of transforming growth factor-beta 1 and procollagen type I. A postoperative fiber-free liquid diet also may be detrimental to the expression of these transcripts in the bowel. Alternative methods for delivery of colonic fuels are needed to create a better environment for colonic healing while eliminating bacteria and bulk.

Anastomosis, Surgical↗
PubMed1997

Relevance of irinotecan hydrochloride-induced diarrhea to the level of prostaglandin E2 and water absorption of large intestine in rats.

For characterization of the mechanism(s) of severe diarrhea due to the anticancer agent, irinotecan hydrochloride (CPT-11), examination was made of the relation of CPT-11-related diarrhea to colonic prostaglandin E2 (PGE2) and water absorption in rats. Acute diarrheal symptoms were observed within 1 hr after the administration of CPT-11 to rats, with increased PGE2 and decreased water absorption in the colon. Treatment with atropine at 1 mg/kg, s.c. was noted to inhibit intestinal PGE2 and the CPT-11-related acute diarrheal symptoms, indicating that these diarrheal symptoms were mediated through the cholinergic nervous system accelerated functionally by CPT-11. On the other hand, daily treatment of CPT-11 at the same dose resulted in chronic diarrheal symptoms in all animals 3 days after CPT-11 treatment. Histopathological changes observed in the descending colon and ileum of the rats included degeneration and necrosis of villi and cryptal cells and a decrease in the number of the goblet cells. Significantly increased PGE2 and impaired water absorption of the descending colon were also observed during the chronic diarrheal stage. It can be considered that the chronic diarrheal symptoms appear as a consequence of the gastrointestinal injury characterized by significant increase in PGE2 accompanied by impaired water absorption.

Animals↗
PubMed2003

No volume effect on retrograde colonic spread of rectally-administered ropivacaine gel.

BACKGROUND: Rectal administration of enemas, foams and suppositories is the most efficient way to deliver locally acting drugs to the distal colon. Ropivacaine, a long-acting local anaesthetic, was chosen as a candidate for a new rectal treatment of ulcerative colitis. AIM: To determine the colonic spread of a rectal ropivacaine formulation. METHODS: In this randomized, incomplete cross-over study, 12 male volunteers were given 200 mg ropivacaine HCl rectally in 20, 40, 60 and 80 mL hydroxypropyl methylcellulose gel. The viscosity of the gel was 1.1 Pa s. The spread of the radiolabelled (99mTc-labelled diethylenetriaminepenta-acetic acid) formulations was assessed by gamma-scintigraphy. Plasma was collected and analysed for ropivacaine base. RESULTS: The retrograde spread was limited to the descending colon and the difference between the studied volumes was not statistically significant. Only the 80-mL volume tended to have a larger distribution, although the 20-mL volume showed the same maximal distribution in two subjects. No distinct relationship between volume, retrograde colonic spread and plasma concentrations could be found. Ropivacaine was well tolerated. CONCLUSIONS: Rectal ropivacaine gel in all volumes between 20 and 80 mL can spread up to the descending colon. There was no relationship between either retrograde colonic spread or the administered volume and the ropivacaine plasma concentrations.

Administration, Rectal↗