INFLAMMATORY BOWEL DISEASES, Issue 5 2010
Norman R. Harris PhD
Abstract Background: Adoptive transfer of naive T-lymphocyte subsets into lymphopenic mice initiates chronic gut inflammation that mimics several aspects of inflammatory bowel disease (IBD). Patients with IBD can have profound alterations in intestinal blood flow, but whether the same is true in the T-cell transfer model has yet to be determined. Methods: In the current study, chronic intestinal inflammation was induced in recombinase-activating gene-1-deficient (RAG,/,) mice by adoptive transfer of CD4+ T-lymphocytes obtained from interleukin-10 deficient (IL-10,/,) mice. Results: Four weeks later, widespread colonic inflammation was observed in the reconstituted recipients, in contrast to 2 control sets of mice injected with a different subset of lymphocytes or with vehicle alone. We observed that the resulting pathology induced in the reconstituted RAG,/, mice was divided distinctly into 2 subsets: 1 with blood flow near normal with very high inflammation scores, and the other with severely attenuated blood flow but with much lower signs of inflammation. Colonic and ileal blood flow rates in the latter subset of CD4+ mice averaged only ,30% compared to the mice with higher inflammation scores. The lower blood flow rates were associated with greatly reduced red blood cell concentrations in the tissue, suggesting a possible loss of vascular density. Conclusions: In this model of chronic intestinal inflammation, mild inflammation was associated with significant decreases in blood flow. Inflamm Bowel Dis 2009 [source]

Discrepancy between recalled and recorded bowel habits in irritable bowel syndrome

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010
M. Coletta
Aliment Pharmacol Ther 2010; 32: 282ash;288 Summary Background, A discrepancy between recalled and recorded bowel habit subtypes has been reported in irritable bowel syndrome (IBS), but the reasons for it remain unclear. Aim, To assess the agreement between recalled and recorded bowel habit subtypes; to determine whether any discrepancy is related to stool form variability or psychological factors; and to test the correlations of recalled and recorded stool form with colonic transit time. Methods, Bowel habit subtype was established in 54 IBS patients at the enrolment visit (recalled) and with the aid of diary cards (recorded). Colonic transit time, the variability of stool form and the patients' psychological profiles were also recorded. Results, Recalled and recorded bowel habit subtypes agreed in only 54% of the patients (kappa = 0.28). Stool form variability was greater among the patients whose recalled and recorded bowel habit subtypes were discordant (P = 0.03), whereas the psychological profiles were not different. Colonic transit time significantly correlated with stool form only when it was recorded on diary cards. Conclusion, The discrepancy between recalled and recorded bowel habits in IBS patients is related more to stool form variability than an altered psychological profile. Diary cards should be used to ensure that stool form reflects colonic transit time. [source]

Colonic and small-intestinal phenotypes in gastric cancers: Relationships with clinicopathological findings

PATHOLOGY INTERNATIONAL, Issue 10 2005
Tsutomu Mizoshita
The clinicopathological significance of colonic and small-intestinal phenotypes has hitherto remained unclear in gastric cancers. The purpose of the present study was therefore to examine 86 gastric carcinomas histologically and phenotypically using several phenotypic markers, including colon-specific carbonic anhydrase 1 (CA1) and sucrase as small-intestine specific marker. Of 86 gastric cancers, sucrase and CA1 expression was observed in 12 (14.0%) and only in two cases (2.3%), respectively, associated with other intestinal markers such as villin and mucin core protein (MUC)2. In the sucrase cases, expression appeared independent of the stage. However, CA1 expression was observed only in two advanced cases. No association was observed between colonic and small-intestinal phenotypes, and lymph node metastasis and postoperative survival in the advanced gastric cancer cases with intestinal phenotypic expression. Cdx2 appeared to be linked to upregulation of both CA1 and sucrase. In conclusion, the data suggest that colonic phenotype occurs rarely in gastric carcinogenesis. Colonic and small-intestinal phenotypes appear with expression of several intestinal phenotypic markers under the control of Cdx2 and presumably other related transcription factors. [source]

Diagnostic utility of mammaglobin and GCDFP-15 in the identification of metastatic breast carcinoma in fluid specimens

DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2009
Z. Yan M.D.
Abstract Morphologic differentiation of breast carcinoma from nonmammary malignancies in fluid specimens can be a diagnostic challenge. Immunocytochemistry is often employed in the differential diagnosis. In this study, we evaluated the expression of mammoglobin (MGB1) in body-cavity fluid specimens and compared its efficacy as a marker for metastatic breast carcinomas with that of gross cystic disease fluid protein-15 (GCDFP-15). Cell blocks from 40 fluid specimens were immunostained with monoclonal antibodies against MGB1 and GCDFP-15. They included 15 breast carcinomas and 25 nonmammary carcinomas (10 lungs, 10 ovaries, 3 gastrointestinal tracts, 1 kidney, and 1 urinary bladder). Positivity was defined as the presence of cytoplasmic staining in 10% or more carcinoma cells. Thirteen (87%) and seven (47%) breast carcinomas showed positive staining with MGB1 and GCDFP-15, respectively. Three (12%) nonmammary carcinomas (2 ovarian and 1 colonic) showed positive MGB1 staining; one (3%) nonmammary carcinoma demonstrated positive GCDFP-15 staining. The differences of MGB1 and GCDFP-15 staining between breast and nonmammary carcinomas were statistically significant (P < 0.05). Both MGB1 and GCDFP-15 are specific markers for metastatic breast carcinomas in cell block fluid specimens (88 vs. 96%). However, MGB1 is more sensitive than GCDFP-15 as a marker for metastatic breast carcinoma (87 vs. 46%). Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]

Recurrent colics in a 9-year-old Arabian stallion due to several congenital anomalies

EQUINE VETERINARY EDUCATION, Issue 11 2008
M. P. Robert
Summary A 9-year-old Arabian stallion was presented for evaluation of recurrent colic problems of 2 years' duration. These colic episodes were associated with a right sided abdominal distension. An exploratory laparotomy revealed a colonic diverticulum that was resected en bloc. Two days later, following signs of acute colic, a second laparotomy showed incarceration of the distal jejunum into a mesodiverticular band combined with haemorrhage of a mesenteric arterial branch. In addition, an abnormally short jejunum (10 m) was also observed. An end-to-end jejunojejunostomy was performed. Following surgery the horse developed septic peritonitis, ptyalism and became dysphagic. Ten days after the second surgery, an infected oesophageal diverticulum causing regional inflammation was diagnosed endoscopically and euthanasia was performed. Post mortem examination showed a 40 cm long diverticulum lateral to the oesophagus. Histology suggested a congenital nature of the colonic and oesophageal diverticuli. [source]

Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohn's disease in an Australian population

INFLAMMATORY BOWEL DISEASES, Issue 5 2008
Georgia E. Hume MD
Abstract Background: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll-like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta-analysis. Methods: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case-control analysis prior to and after stratification by NOD2 genotype. Genotype,phenotype relationships were also sought. Meta-analysis was conducted via RevMan. Results: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta-analysis of 11 CD cohorts identified a 1.5-fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). Conclusions:TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes. (Inflamm Bowel Dis 2007) [source]

Efficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn's disease: A single-center experience

INFLAMMATORY BOWEL DISEASES, Issue 1 2008
Aaron Benson MD
Abstract Background: The published experience regarding the use of tacrolimus in Crohn's disease (CD) and ulcerative colitis (UC) refractory to more commonly used medical therapy has been fairly limited. Our objective was to describe our experience with its use in a cohort of patients which, to our knowledge, represents the largest North American cohort described to date. Methods: This was a retrospective, single-center chart analysis. Patients were identified by compiling all hospital discharges with principle diagnoses of ICD-9 codes for 555.0-555.9 (regional enteritis) and 556.0-556.9 (ulcerative colitis) from January 1, 2000, to October 31, 2005, and then cross-referencing the electronic charts for tacrolimus serum concentrations ordered during this time period. Additional patients were identified through verbal communication with participating clinicians. Information abstracted included proportion with clinical response and remission (using a modified disease activity index), ability to wean from steroids, need for surgery / time to surgery, and side-effect profile. Results: In all, 32 UC patients and 15 CD patients were identified. The mean disease duration was: UC 81 months (range, 1 month to 37 years), CD 100 months (range, 1 month to 35 years). The disease distribution for UC was: pancolitis 12 (37.5%), extensive colitis 6 (18.8%), left-sided 11 (34.4%), and proctitis 3(9.4%). For CD this was: TI 2 (13.3%), small bowel 2 (13.3%), colonic 3 (20.7%), ileocolonic 7(46.7%), and perianal 1 (6.7%). The duration of tacrolimus treatment for UC was mean, 29 weeks. For CD it was mean, 9.9 weeks. In all, 30/32 UC and 7/15 CD patients were on steroids; 4/30 UC and 0/7 CD patients were able to subsequently wean off steroids. In all, 12/32 UC patients proceeded to colectomy. Mean time to colectomy was 28 weeks and 6/15 CD patients proceeded to a resective surgery. The mean time to surgery was 22 weeks. In all, 22/32 UC patients achieved a clinical response; 3/32 achieved remission and 8/15 CD patients achieved a clinical response; 1/15 achieved remission. Adverse reactions were generally mild. In 6 patients the drug had to be discontinued because of an adverse reaction. There were no opportunistic infections identified, no cases of renal insufficiency related to drug administration, and no deaths while on the medicine. Conclusions: Our experience with tacrolimus in UC and CD indicates that it is safe and relatively well tolerated, although its clinical efficacy is quite variable. More prospective studies assessing its use are necessary. (Inflamm Bowel Dis 2007) [source]

Dual-association of gnotobiotic Il-10,/, mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis

INFLAMMATORY BOWEL DISEASES, Issue 12 2007
Sandra C. Kim MD
Abstract Background: Monoassociating gnotobiotic IL-10-deficient (,/,) mice with either nonpathogenic Enterococcus faecalis or a nonpathogenic Escherichia coli strain induces T-cell-mediated colitis with different kinetics and anatomical location (E. faecalis: late onset, distal colonic; E. coli: early onset, cecal). Hypothesis: E. faecalis and E. coli act in an additive manner to induce more aggressive colitis than disease induced by each bacterial species independently. Methods: Germ-free (GF) inbred 129S6/SvEv IL-10,/, and wildtype (WT) mice inoculated with nonpathogenic E. faecalis and/or E. coli were killed 3,7 weeks later. Colonic segments were scored histologically for inflammation (0 to 4) or incubated in media overnight to measure spontaneous IL-12/IL-23p40 secretion. Bacterial species were quantified by serial dilution and plated on culture media. Mesenteric lymph node (MLN) CD4+ cells were stimulated with antigen-presenting cells pulsed with bacterial lysate (E. faecalis, E. coli, Bacteroides vulgatus) or KLH (unrelated antigen control). IFN-, and IL-17 levels were measured in the supernatants. Results: Dual-associated IL-10,/, (but not WT) mice developed mild-to-moderate pancolitis by 3 weeks that progressed to severe distal colonic-predominant pancolitis with reactive atypia and duodenal inflammation by 7 weeks. NF-,B was activated in the duodenum and colon in dual-associated IL-10,/, × NF-,BEGFP mice. The aggressiveness of intestinal inflammation and the degree of antigen-specific CD4+ cell activation were greater in dual- versus monoassociated IL-10,/, mice. Conclusion: Two commensal bacteria that individually induce phenotypically distinct colitis in gnotobiotic IL-10,/, mice act additively to induce aggressive pancolitis and duodenal inflammation. (Inflamm Bowel Dis 2007) [source]

5-Aminosalicylic acid (mesalazine) use in Crohn's disease: A survey of the opinions and practice of Australian gastroenterologists

INFLAMMATORY BOWEL DISEASES, Issue 8 2007
Richard B. Gearry MD
Abstract Background: The use of 5-aminosalicylate (5-ASA) drugs in Crohn's disease (CD) is controversial, with their continuing apparent widespread use despite high-level evidence indicating marginal benefit at best and international guidelines recommending limited indications. Methods: In order to understand how clinicians translate the evidence base into clinical practice, we surveyed a cross-section of Australian gastroenterologists to determine opinions and prescribing patterns of 5-ASA drugs in CD. Results: In all, 42% of 285 gastroenterologists who were sent a questionnaire by e-mail responded. Five (4%) never use 5-ASA drugs in CD. The drugs are most commonly prescribed for patients with colonic (96%) or ileocolonic (92%) disease location, inflammatory disease behavior (80%), and mild disease activity (97%). The majority (64%) use a dose of 1,3 g/day, but only 6% use over 4.5 g/day. Less than one-half use 5-ASA drugs as maintenance following surgical resection, but most use it for inducing remission alone (70%) or in combination with other drugs (90%), and continue its use for maintenance. Side effects are thought to be infrequent (62%) or rare (20%) and few common side effects are believed to be serious. Respondents estimated that over 90% of patients were nonadherent to prescribed 5-ASA regimens at least 50% of the time. While 84% believed that 5-ASA drugs were effective in CD, only 58% believed that they were cost-effective. Conclusions: In Australia 5-ASA drugs are extensively prescribed for CD at relatively low doses without expectation of patient adherence. Current evidence and guidelines has had little apparent impact on clinical practice. The cost implications are considerable. (Inflamm Bowel Dis 2007) [source]

Characterization of colonic and mesenteric lymph node dendritic cell subpopulations in a murine adoptive transfer model of inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 6 2004
John Karlis BScHons
Abstract Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (TH1) type cell response, whereas ulcerative colitis is predominantly associated with a TH2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b+ B220, myeloid dendritic cells and 50% expressed the CD11b, B220+ plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-, in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD. [source]

Immunohistochemical assessment of parafibromin in mouse and human tissues

JOURNAL OF ANATOMY, Issue 6 2006
Andrea Porzionato
Abstract Parafibromin is a protein encoded by the HRPT2 oncosuppressor gene, whose mutation causes the hyperparathyroidism,jaw tumour syndrome, characterized by the occurrence of parathyroid adenoma or carcinoma, fibro-osseous jaw tumours, and renal neoplastic and non-neoplastic abnormalities. Non-morphological techniques, such as Northern and Western blotting and reverse transcriptase-PCR, indicate that parafibromin is ubiquitously expressed, but extensive immunohistochemical studies have not been performed. To increase our knowledge of the distribution and patterns of expression of parafibromin, we examined its expression and location in many different mouse and human organs by immunohistochemistry. There were no substantial differences in parafibromin expression between mouse and human. We found widespread expression of parafibromin, except in connective tissue, smooth muscle, endothelium and some other types of epithelia (colonic, urinary, tubaric, uterine, thyroid). Heterogeneity of positivity intensity and subcellular location (nuclear, nucleocytoplasmic, cytoplasmic) was found between tissues and cell types, suggesting differential functional involvement of parafibromin. Moreover, higher parafibromin expression was found in cell types, such as hepatocytes, cells of the base of gastric glands, renal cortex tubules and the pars intermedia of the hypophysis, which are characterized by different proliferative capacity, thus indicating that the cellular function of parafibromin may not be reduced only to its anti-proliferative effect. [source]

Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009
S. KVOLIK
Background: The aim of this study was to determine the effect of a single exposure of carcinoma cells (Caco-2 and HEp-2) to an anaesthetic gas mixture containing sevoflurane 3%, applied for a period of either 1 or 2 h, on the induction of apoptosis, propapototic gene expression and sphingomyelinase activity. Methods: Apoptosis was determined by flow cytometry. p53, caspase 3 and CYP2E1 gene expression was determined using reverse transcriptase polymerase chain reaction. Activities of acid (aSMase) and neutral sphingomyelinases (nSMase) were measured using methyl- 14C sphingomyeline, and for de novo ceramide and lipid synthesis [3H] palmitic acid was used. All results were compared with controls and analysed by Mann,Whitney and Kruskal,Wallis tests. Results: In the treated Caco-2 cells, the apoptotic ratio increased 24 h after anaesthesia (16.9%; P=0.04). The expression of both p53 and caspase-3 genes increased in Caco-2 and decreased in HEp-2 cells. The CYP2E1 gene expression was observed only in the Caco-2 cells. In control cells, the catalytic activity of aSMase was 2.3 times higher than that of nSMase activity. Decreased aSMase and nSMase activities were observed in Caco-2 cells 24 h after exposition. aSMase activity was halved (54.2%; P=0.06) in HEp-2 cells 24 h after anaesthesia. De novo ceramide synthesis correlated with SMase activity in Caco-2 cells. Conclusion: Sevoflurane anaesthesia induces late apoptosis in the colonic and laryngeal cancer cells investigated. Although the results obtained may indicate that an anaesthetic gas mixture containing sevoflurane induces p53-dependent apoptosis in the Caco-2 cells, the mechanism of apoptosis induction is unclear and remains to be elucidated. [source]

Reasons for creation of permanent ileostomy for the management of idiopathic chronic constipation

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2004
AM EL-TAWIL
Abstract The aim of the present study was to examine the reasons for initiation of end ileostomy for management of intractable constipation over the last 35 years. A total of 62 patients with intractable constipation, on whom an end ileostomy was created during the period from 1966 to 2001, were recorded. The incidence of initiating a terminal ileostomy as a further surgical intervention to the total number of managed patients in examined studies varied from 2 to 25%. Preoperative unevaluated anal and rectal abnormalities formed the highest proportion compared with other reasons (65%, 40/62). A better understanding of the functional colonic and anorectal abnormalities may facilitate changes in surgical therapy. [source]

MR colonography for the assessment of colonic anastomoses

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2006
Waleed Ajaj MD
Abstract Purpose To assess colonic anastomoses in patients after surgical treatment by means of MR colonography (MRC) in comparison with conventional colonoscopy (CC). Materials and Methods A total of 39 patients who had previously undergone colonic resection and end-to-end-anastomosis were included in the study. MRI was based on a dark-lumen approach. Contrast-enhanced T1-weighted (T1w) three-dimensional (3D) images were collected following the rectal administration of water for colonic distension. The MRC data were evaluated by two radiologists. The criteria employed to evaluate the anastomoses included bowel wall thickening and increased contrast uptake in this region. Furthermore, all other colonic segments were assessed for the presence of pathologies. Results In 23 and 20 patients the anastomosis was rated to be normal by MRC and CC, respectively. In three patients CC revealed a slight inflammation of the anastomosis that was missed by MRI. A moderate stenosis of the anastomosis without inflammation was detected by MRC in five patients, which was confirmed by CC. In the remaining 11 patients a relevant pathology of the anastomosis was diagnosed by both MRC and CC. Recurrent tumor was diagnosed in two patients with a history of colorectal carcinoma. In the other nine patients inflammation of the anastomosis was seen in seven with Crohn's disease (CD) and two with ulcerative colitis. MRC did not yield any false-positive findings, resulting in an overall sensitivity/specificity for the assessment of the anastomosis of 84%/100%. Conclusion MRC represents a promising alternative to CC for the assessment of colonic anastomoses in patients with previous colonic resection. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [source]

Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesis

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006
Muthaiyan Kamaleeswari
Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg,1 (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg,1 for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P < 0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and ,-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P < 0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg,1 had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats. [source]

The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010
B. S. Wong
Aliment Pharmacol Ther 2010; 32: 884,893 Summary Background, The short-term effects of methylnaltrexone (MNTX), a peripherally acting ,-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. Aim, To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. Methods, In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Results, Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t1/2 (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Conclusion, Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health. [source]

Discrepancy between recalled and recorded bowel habits in irritable bowel syndrome

Spatial variation of intestinal skatole production and microbial community in Jinhua and Landrace pigs,

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 4 2009
Cai-Yan Li
Abstract BACKGROUND: An excessive accumulation of skatole in pigs is a major contributor to boar taint. Intestinal skatole concentrations may vary among different pig segments and breeds. The objective of this study was to evaluate the spatial variation of intestinal skatole production and the microbial community in local Jinhua and exotic Landrace pigs. RESULTS: For both breeds, skatole concentration increased towards the rectum and segment had a significant effect on skatole (P < 0.001). The caecal skatole concentration in Landrace was significantly lower than proximal, distal colonic and rectal skatole levels (P < 0.05). Compared with Jinhua pigs, the rectal skatole and proximal and distal colonic indole levels were significantly higher in Landrace pigs (P < 0.05). Volatile fatty acids were significantly affected by breed except for isobutyrate and isovalerate (P < 0.05), with higher butyrate level and lower pH in Landrace pigs (P < 0.05). There were no significant differences in mitosis and apoptosis for the two breeds. The denaturing gradient gel electrophoresis profile showed differences between breeds and segments within one breed, though some bands were common to all samples. CONCLUSION: The higher skatole levels in Landrace pigs may be not associated with higher intestinal apoptosis. The results suggested that pig genotype plays a role in the establishment of the host-specific microbiota and that the variations in fermentation patterns are more likely to explain differences in intestinal skatole production. Copyright © 2009 Society of Chemical Industry [source]

Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009
N. MANABE
Summary Background, The mechanism of action of bisacodyl in the unprepared human colon remains unclear. Aim, To evaluate the effect of oral bisacodyl on the overall and regional colonic transit in humans. Methods, In a double-blind, randomized, placebo-controlled study of 25 healthy participants, effects of oral bisacodyl (5 mg p.o. per day) and placebo on colonic transit were compared. A validated scintigraphy method was used to measure colonic transit. The primary transit endpoints, ascending colon emptying t1/2 and geometric centre of colon isotope at 24 h (overall transit), were compared (Wilcoxon rank sum test). Results, There were significant treatment effects on ascending colon t1/2, with the bisacodyl group demonstrating accelerated emptying [median 6.5 h, interquartile range 5.0,8.0 h] relative to the placebo group [11.0 h (7.0,17.1); P = 0.03]. Numerical differences in colonic geometric centre 24 h [bisacodyl median 3.0 (2.2,3.8), placebo 4.0 (3.1,4.6)] were not significant (P = 0.19). There were no significant differences observed in geometric centre 4 h. Conclusion, Oral 5 mg bisacodyl accelerates ascending colon in the unprepared colon in healthy adults; this action may contribute to the drug's efficacy in constipation. [source]

Review article: the current and evolving treatment of colonic diverticular disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
A. TURSI
Summary Background, Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea). Aims, To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies. Methods, PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease. Results, Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy. Conclusions, Data suggest that diverticular disease may share many of the hallmarks of other, better-characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly. [source]

Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
I. KÜBLER
Summary Background, Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the ,- and ,-defensins. Little is known about in vivo effects of common drugs on their expression. Aim, To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation. Methods, We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD. Results, Ileal and colonic ,- and ,-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell ,-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples. Conclusions, Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity. [source]

A dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol)

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009
M. P. THORPE
Summary Backround, 5-ASA in a pH sensitive tablet (Asacol) is administered as three doses/day to treat ulcerative colitis. Once daily dosing may improve patient adherence. Simulation of colonic levels of 5-ASA can be used to compare dosing regimens. Aim, To create a dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol). Methods, Using published data, we created a computer model with STELLA software to simulate amounts of colonic 5-ASA in the total colon, right, transverse, descending and sigmoid/rectum after daily and three time/day Asacol. Results, The model predicted similar total and regional amounts of 5-ASA with both regimens. Distribution of 5-ASA was 38% in the right colon, 33% in the transverse colon and 14% each in the descending and sigmoid/rectal colon. Simulated increases in colonic motility and defecation rate exaggerated this 5-ASA distribution, resulting in negligible amounts of 5-ASA in the sigmoid/rectal region. Conclusions, This computer model suggests that Asacol can be administered as a single daily dose. The model supports experimental and clinical observations that alternate dose or route of administration may be necessary to achieve adequate 5-ASA amounts in the distal colon during acute exacerbations of ulcerative colitis. This simulation cannot account for all sources of variability in the clinical setting, but provides a rationale for further investigation. [source]

Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009
A. AGRAWAL
Summary Background, A sensation of abdominal swelling (bloating) and actual increase in girth (distension) are troublesome features of irritable bowel syndrome (IBS), which is more common in patients with constipation, especially those with delayed transit. Aim, To establish whether a fermented dairy product containing Bifidobacterium lactis DN-173 010 reduces distension in association with acceleration of gastrointestinal transit and improvement of symptoms in IBS with constipation. Methods, A single centre, randomized, double-blind, controlled, parallel group study in which patients consumed the test product or control product for 4 weeks. Distension, orocaecal and colonic transit and IBS symptoms were assessed on an intention-to-treat population of 34 patients. Results, Compared with control product, the test product resulted in a significant reduction in the percentage change in maximal distension [median difference , 39%, 95% CI (,78, ,5); P = 0.02] and a trend towards reduced mean distension during the day [,1.52 cm (,3.33, 0.39); P = 0.096]. An acceleration of orocaecal [,1.2 h (,2.3,0); P = 0.049] as well as colonic [,12.2 h (,22.8, ,1.6); P = 0.026] transit was observed and overall symptom severity [,0.5 (,1.0, ,0.05); P = 0.032] also improved. Conclusions, This probiotic resulted in improvements in objectively measured abdominal girth and gastrointestinal transit, as well as reduced symptomatology. These data support the concept that accelerating transit is a useful strategy for treating distension. [source]

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2008
P. NETZER
Summary Background, Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. Aim, To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. Methods, Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. Results, Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. Conclusions, Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects. [source]

Review article: new drug formulations, chemical entities and therapeutic approaches for the management of ulcerative colitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008
S. C. NG
Summary Background, Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. Aim, To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Methods, Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. Results, 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations, and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator-activated receptor-, (PPAR-,) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-, agonists. Conclusion, The evolution of novel oral 5-ASA formulations and dosage regimens, and recent development of new molecules have expanded the therapeutic armamentarium of UC. [source]

Epidemiology of slow and fast colonic transit using a scale of stool form in a community

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2007
R. S. CHOUNG
Summary Background, Measurement of gastrointestinal transit is commonly performed in the clinic, but data on transit in the community are lacking. Aim, To estimate the prevalence of slow and fast colonic transit using stool form, and potential risk factors. Methods, A validated self-reported gastrointestinal symptom questionnaire was mailed to 4196 randomly selected members of the community (response rate 54%). One question asked the subject to self-report their stool form using the Bristol Stool Scale. Results, Overall, 18%, 9% and 73% met stool form criteria for slow, fast or normal colonic transit, respectively. Increased odds for slow transit were observed with a higher Somatic Symptom Checklist score (OR = 1.6; 1.3,2.0), while a decreased odds for slow transit was observed in males relative to females (OR = 0.6; 0.5,0.8). An increased odds for fast transit was observed with higher Somatic Symptom Checklist score (OR = 2.3; 1.7,2.9) and a history of cholecystectomy (OR = 1.8; 1.2,2.8). Increasing body mass index (per 5 units) was associated with decreased odds for slow (OR = 0.85; 0.78,0.93), and an increased odds for fast (OR = 1.1; 1.04,1.24) colonic transit. Conclusion, Based on stool form assessment, nearly one in five community members may have slow colonic transit and one in 12 have accelerated colonic transit. [source]

Review article: uncomplicated diverticular disease of the colon

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006
L. PETRUZZIELLO
Summary Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect healthcare costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed. [source]

Review article: bifidobacteria as probiotic agents , physiological effects and clinical benefits

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2005
C. PICARD
Summary Bifidobacteria, naturally present in the dominant colonic microbiota, represent up to 25% of the cultivable faecal bacteria in adults and 80% in infants. As probiotic agents, bifidobacteria have been studied for their efficacy in the prevention and treatment of a broad spectrum of animal and/or human gastrointestinal disorders, such as colonic transit disorders, intestinal infections, and colonic adenomas and cancer. The aim of this review is to focus on the gastrointestinal effects of bifidobacteria as probiotic agents in animal models and man. The traditional use of bifidobacteria in fermented dairy products and the GRAS (,Generally Recognised As Safe') status of certain strains attest to their safety. Some strains, especially Bifidobacterium animalis strain DN-173 010 which has long been used in fermented dairy products, show high gastrointestinal survival capacity and exhibit probiotic properties in the colon. Bifidobacteria are able to prevent or alleviate infectious diarrhoea through their effects on the immune system and resistance to colonization by pathogens. There is some experimental evidence that certain bifidobacteria may actually protect the host from carcinogenic activity of intestinal flora. Bifidobacteria may exert protective intestinal actions through various mechanisms, and represent promising advances in the fields of prophylaxis and therapy. [source]

Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002
C. H. M. Clemens
Background: Alosetron is a 5-hydroxytryptamine-3 receptor antagonist reducing symptoms in female patients with diarrhoea-predominant irritable bowel syndrome, and is known to increase the colonic transit time. Aim: To study the effect of alosetron on left colonic phasic motility in ambulant non-constipated patients with irritable bowel syndrome and healthy volunteers. Methods: In a double-blind, randomized, crossover design, 10 patients with irritable bowel syndrome and 12 sex- and age-matched volunteers were treated for two 7-day periods with alosetron, 4 mg b.d., or placebo b.d. On day 6 of each treatment period, a six-channel solid-state manometric catheter was positioned in the left colon and 24 h motility was studied on day 7. The periprandial phasic motility around dinnertime was evaluated in the descending and sigmoid colon. The high-amplitude propagated contraction frequency and characteristics were calculated. Results: Alosetron appeared to increase the overall periprandial frequency in the sigmoid colon (P=0.043) and the mean amplitude of colonic contractions in the descending colon (P=0.007). The high-amplitude propagated contraction frequency was higher on alosetron during the second half of the day for patients with irritable bowel syndrome (P=0.002), with increased mean propagation length of high-amplitude propagated contractions (P=0.001). The stool frequency (P=0.024) and stool consistency score (P=0.002) were decreased by alosetron. Conclusions: The 5-hydroxytryptamine-3 receptor antagonist alosetron marginally increased left colonic periprandial phasic motility. Alosetron increased the number and propagation length of high-amplitude propagated contractions, which were paradoxically accompanied by a decrease in stool frequency and a firming of stool consistency. [source]

Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001
B. Coulie
Background: Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. Aims: (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. Methods: In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. Results: In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. Conclusions: Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects. [source]