Antidiarrhoeal properties of a novel sigma ligand (JO 2871) on toxigenic diarrhoea in mice: mechanisms of action.
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BACKGROUND AND AIMS: Sigma ligands display antisecretory activity against various secretagogues, suggesting antidiarrhoeal properties. In this study, we evaluated: (i) the antidiarrhoeal effect of JO 2871, a high affinity sigma ligand, in three models of toxigenic diarrhoea in mice; and (ii) the site and mechanism of action of this compound. METHODS: Faeces were collected after toxin or vehicle administration in male DBA2 or NMRI mice. Diarrhoea was determined by cumulative stool weight (mg) over a 120 minute period. Diarrhoea was induced by intravenous administration of Salmonella enteriditis lipopolysaccharide (LPS), or oral administration of Escherichia coli heat stable (E coli-sta) or Clostridium difficile toxins. Two sigma ligands, igmesine and JO 2871, were administered either orally or intravenously, 60 and 30 minutes before the toxins, respectively. JO 2871 was also given orally 30 minutes after E coli-sta. In addition, JO 2871 was administered intracerebroventricularly five minutes before LPS and E coli-sta. BMY 14802 (1000 microg/kg orally), a sigma receptor antagonist, or cyclosomatostatin (CSS 1 microg/kg intravenously), a somatostatin antagonist, were given five minutes prior to JO 2871 in LPS, E coli-sta, and C difficile toxin treated mice. Gastric emptying and intestinal transit were evaluated after oral JO 2871 and BMY 14802 and intravenous CSS. RESULTS: Stool weight measured 120 minutes after administration of the toxins was significantly increased. Oral JO 2871 and igmesine dose dependently inhibited toxigenic diarrhoea in all models. ED(50) values obtained using JO 2871 (1-20 microg/kg) were more than 40 times lower than those obtained with igmesine. Oral JO 2871 given after E coli-sta also inhibited diarrhoea in a dose dependent manner (ED(50) 50 microg/kg). Both sigma ligands were active by the intravenous route on LPS and E coli-sta induced stool weight increases. JO 2871 administered intracerebroventricularly failed to block this effect at any dose tested. Both BMY 14802 and CSS reversed the antidiarrhoeal effect of oral JO 2871. JO 2871, BMY 14802, and CSS did not affect transit parameters. CONCLUSIONS: JO 2871 exerts a potent oral antidiarrhoeal effect, acting peripherally through sigma sites and somatostatin release. (+info)
Daily bowel movements and Escherichia coli O157 infection.
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The usual bowel habits of 259 school age children before the large outbreak of E coli O157 infection in Sakai City in the summer of 1996 were investigated. A daily morning movement and/or frequent bowel movements may be a protective factor against infection, while being constipated contributed to a worsening of symptoms. (+info)
Genetic linkage mapping of quantitative trait loci for behavioral and neuroendocrine stress response traits in pigs.
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A QTL analysis of behavioral and neuroendocrine responses to a "novel environment" stress was conducted in a three-generation experimental cross between Meishan and Large White pig breeds. A total of 186 F2 males and 182 F2 females were studied for their behavioral and neuroendocrine reactivity to a novel environment test at 6 wk of age. Locomotion, vocalization, and defecation rate, as well as exploration time, were measured for 10 min. Blood samples were taken immediately before and after the test to measure plasma levels of ACTH, cortisol, and glucose. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using two interval mapping methods: a line-cross regression method, where founder lines were assumed to be fixed for different QTL alleles, and a half-/full-sib maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Both methods revealed a highly significant gene effect for poststress cortisol level (P < 0.001) and a significant effect for basal cortisol level (P < 0.05) at the end of the q arm of chromosome 7, explaining, respectively, 20% and 7% of the phenotypic variance. Meishan alleles are associated with higher cortisol levels and are partially dominant (for poststress levels) over Large White alleles. Other significant gene effects on biological measures were detected on chromosomes 1 and 17 (ACTH response to stress), 3, 5, and 8 (glucose levels). The SSC 17 QTL explains 12% of the phenotypic variance of poststress ACTH levels, with a suggestive evidence of imprinting effects. Meishan alleles are associated with lower poststress ACTH levels. Gene effects of low amplitude only were found for behavioral reactivity traits. Considering the effects of stress neuroendocrine systems on energy fluxes and protein deposition, and the importance of stress reactivity for meat quality and animal welfare, these results open new perspectives for pig selection. (+info)
Is anorectal endosonography valuable in dyschesia?
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AIMS: Dyschesia can be provoked by inappropriate defecation movements. The aim of this prospective study was to demonstrate dysfunction of the anal sphincter and/or the musculus (m.) puborectalis in patients with dyschesia using anorectal endosonography. METHODS: Twenty consecutive patients with a medical history of dyschesia and a control group of 20 healthy subjects underwent linear anorectal endosonography (Toshiba models IUV 5060 and PVL-625 RT). In both groups, the dimensions of the anal sphincter and the m. puborectalis were measured at rest, and during voluntary squeezing and straining. Statistical analysis was performed within and between the two groups. RESULTS: The anal sphincter became paradoxically shorter and/or thicker during straining (versus the resting state) in 85% of patients but in only 35% of control subjects. Changes in sphincter length were statistically significantly different (p<0.01, chi(2) test) in patients compared with control subjects. The m. puborectalis became paradoxically shorter and/or thicker during straining in 80% of patients but in only 30% of controls. Both the changes in length and thickness of the m. puborectalis were significantly different (p<0.01, chi(2) test) in patients versus control subjects. CONCLUSIONS: Linear anorectal endosonography demonstrated incomplete or even absent relaxation of the anal sphincter and the m. puborectalis during a defecation movement in the majority of our patients with dyschesia. This study highlights the value of this elegant ultrasonographic technique in the diagnosis of "pelvic floor dyssynergia" or "anismus". (+info)
Outcomes after total versus subtotal abdominal hysterectomy.
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BACKGROUND: It is uncertain whether subtotal abdominal hysterectomy results in better bladder, bowel, or sexual function than total abdominal hysterectomy. METHODS: We conducted a randomized, double-blind trial comparing total and subtotal abdominal hysterectomy in 279 women referred for hysterectomy because of benign disease; most of the women were premenopausal. The main outcomes were measures of bladder, bowel, and sexual function at 12 months. We also evaluated postoperative complications. RESULTS: The rates of urinary frequency (urination more than seven times during the day) were 33 percent in the subtotal-hysterectomy group and 31 percent in the total-hysterectomy group before surgery, and they fell to 24 percent and 20 percent, respectively, at 12 months (P=0.03 for the change over time within each group; P=0.84 for the interaction between the treatment assignment and time). The reduction in nocturia and stress incontinence and the improvement in bladder capacity were similar in the two groups. The frequency of bowel symptoms (as indicated by reported constipation and use of laxatives) and measures of sexual function (including the frequency of intercourse and orgasm and the rating of the sexual relationship with a partner) did not change significantly in either group after surgery. The women in the subtotal-hysterectomy group had a shorter hospital stay (5.2 days, vs. 6.0 in the total-hysterectomy group; P=0.04) and a lower rate of fever (6 percent vs. 19 percent, P<0.001). After subtotal abdominal hysterectomy, 7 percent of women had cyclical bleeding and 2 percent had cervical prolapse. CONCLUSIONS: Neither subtotal nor total abdominal hysterectomy adversely affects pelvic organ function at 12 months. Subtotal abdominal hysterectomy results in more rapid recovery and fewer short-term complications but infrequently causes cyclical bleeding or cervical prolapse. (+info)
Dietary L-lysine deficiency increases stress-induced anxiety and fecal excretion in rats.
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Little is known about the psychobehavioral consequences of a dietary deficiency of the amino acid, L-lysine. This report demonstrates that a 4-d long L-lysine deficiency in rats interfered with the normal circadian release of the neurotransmitter serotonin, but not dopamine, measured by in vivo microdialysis in the central nucleus of the amygdala. L-Lysine deficiency was induced by feeding rats a L-lysine-deficient diet. Controls were pair-fed a L-lysine-sufficient diet. Footshock stress-induced anxiety, measured in an elevated plus-maze paradigm, and wrap-restraint stress-stimulated fecal excretion were significantly greater in the L-lysine-deficient rats than in the controls. We conclude that a severe deficiency of dietary L-lysine enhances serotonin release in the amygdala, with subsequent changes in psychobehavioral responses to stress. (+info)
Feeding and defaecation behaviour of Triatoma patagonica (Del Ponte, 1929) (Hemiptera: Reduviidae).
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Among the vectors of Chagas disease, Triatoma patagonica is a species in the process of adaptation to the human environment being recently registered in urban and suburban zones. However, its importance as a vector of Chagas disease is unknown. The aim of this work was to evaluate two aspects of vectorial competence: the feeding behaviour and the defaecation pattern. These processes were studied in females of T. patagonica fed ad libitum on a restrained pigeon. The results showed that the blood meal size was negatively correlated with the time of first defaecation (r = -0.42). The first defaecation was emitted before the first 10 min and defaecations during feeding were frequent. A total of 73% of females, defaecated during the first 30 min post-feeding. These results suggest that if this species subsequently colonizes the domicile, it would be capable of transmitting Trypanosoma cruzi. (+info)
Dietary fibre content and nutrient claims relative to the faecal bulking efficacy of breakfast cereals.
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The correspondence between the dietary fibre contents of 28 breakfast cereals and their faecal bulking efficacies was measured and used to assess criterion values controlling nutrient claims for dietary fibre. A valid, standardised rat assay was used to measure faecal bulking efficacy as the content of wheat bran equivalents for faecal bulk (WBEfb) in the cereals. Regression analysis of WBEfb content against dietary fibre content allowed the adequacy of criterion fibre values for claims of 'source of fibre,' 'high in fibre' and 'very high in fibre' to be assessed relative to a daily reference requirement of 63 WBEfb, based on human data. Faecal bulking by breakfast cereals was much lower than implied by the dietary fibre claims associated with them. Many more were claimed to be 'high' or 'very high' in dietary fibre (n = 13) than were 'high' or 'very high' in faecal bulking efficacy (n = 4). Conversely, dietary fibre requirements per serving predicted from WBEfb requirements, as necessary to maintain adequate faecal bulk in the current Australian diet, were much higher (4.4 g) than the criterion fibre content (1.5 g) for the most modest claim, 'source of fibre'. After removing four high-bran cereals (>15% dietary fibre) from the analysis, a modest correlation of r = 0.62 between dietary fibre content and faecal bulk was obtained. It is concluded that, with respect to breakfast cereals, fibre values specified for nutrient claims are too low, dietary fibre content is not a reliable guide to faecal bulking efficacy and direct measures of faecal bulking capacity would be more useful than dietary fibre content in describing faecal bulking efficacy for evidence-based food choice. (+info)