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Chronic naltrexone treatment of rats: effects on gastrointestinal opioid peptide content.

The gastrointestinal tract contains immunoreactive enkephalins and beta-endorphin. The objective of the current study was to determine whether chronic treatment of rats with naltrexone altered the gastrointestinal tissue content of these opioid peptides. Opioid activity measured by radioreceptor assay was detectable throughout the gastrointestinal tract. There were regional differences in the [Met5]enkephalin: [Leu5]enkephalin-immunoreactivity (IR) ratios, possibly due to cell specific differential processing of precursor molecules or degradation of the peptides. Chronic naltrexone treatment increased opioid activity in the duodenum and jejunum, decreased [Met5]enkephalin-IR in the duodenum and [Leu5]enkephalin-IR in the gastric corpus, and increased beta-endorphin-IR in the duodenum. However, the changes were small, and it is unlikely that any functional changes resulting from naltrexone treatment can be reliably ascribed to such changes in tissue content.

Animals↗

Regulatory peptide and serotonin content and brush-border enzyme activity in the rat gastrointestinal tract following neonatal treatment with capsaicin; lack of effect on epithelial markers.

The possible trophic influence of the capsaicin-sensitive extrinsic innervation of the gastrointestinal mucosa was investigated. Rats were treated neonatally with capsaicin. The gastrointestinal content of serotonin and glucagon-like immunoreactivity were used as a measure of the effect on the endocrine gut mucosa and gastrointestinal aminopeptidase and alkaline phosphatase activities were used as a measure of the effect on the gut brush-border. The gastrointestinal content of the neuropeptides substance P, VIP and CGRP were used to monitor effects on the innervation of the gut. The depletion of substance P-immunoreactivity(-IR) and calcitonin gene-related peptide(CGRP)-IR in extracts of urinary bladder and lung from the capsaicin-treated rats is evidence of the efficacy of capsaicin treatment in affecting a loss of C-fibre sensory nerves. The significant depletion of CGRP-IR measured in the stomach and duodenum of capsaicin-treated rats indicated the loss of the C-fibre sensory innervation to the gastrointestinal tract. The gastrointestinal content of VIP and substance P, which are predominantly within intrinsic gut neurones, were unaffected by capsaicin treatment. In all regions of the gastrointestinal tract of capsaicin-treated rats, the serotonin and glucagon-IR levels were not significantly different from those in controls. Similarly the levels of activity of the brush-border enzymes were not significantly effected by capsaicin treatment. This suggest the absence of any major trophic influence of capsaicin-sensitive sensory nerves on the gut endocrine mucosa and the brush border.

Alkaline Phosphatase↗

Gastrointestinal transit in an animal model of human diabetes type 2: relationship to gut neuroendocrine peptide contents.

Gastrointestinal transit (GIT) was determined in obese diabetic mice (ob/ob, Umeå/Bom). Blood glucose level, and insulin concentration in the serum and pancreas extracts as well as neuroendocrine peptide contents were measured in several segments of the gut. GIT was significantly slower in the obese diabetic mice, but was not correlated with the blood glucose level, serum insulin, or pancreatic insulin content. GIT was correlated with duodenal secretin content and colonic vasoactive intestinal peptide (VIP) content, but not with the content of other neuroendocrine peptides in different segments investigated. The antral gastrin content in obese diabetic mice was significantly higher than in controls. The concentration of secretin in obese diabetic mice was higher than in controls. Whereas the contents of peptide YY (PYY) and somatostatin were higher in obese diabetic mice, the contents of substance P and VIP were lower. The increased content of duodenal secretin and decreased content of colonic VIP may be among the factors that cause slow GIT in obese diabetic mice. The changes in the colonic contents of PYY, VIP and somatostatin may cause low intestinal secretion and, together with slow GIT, give rise to constipation, which is a common symptom in diabetes.

Animals↗

Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery: hydrolysis in rat gastrointestinal tract contents.

Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently treated with glucocorticoids and other antiinflammatory agents. Side effects limit chronic glucocorticoid therapy. The dose, and consequently the side effects, may be reduced by using prodrugs that selectively deliver drug to the colon. We previously synthesized glucocorticoid-dextran conjugates in which dexamethasone and methylprednisolone were attached to dextran (weight-average molecular weight = 72,600) using dicarboxylic acid linkers (succinate and glutarate). In the present study, the hydrolysis kinetics of the hemiesters (hemiester = glucocorticoid+linker) and dextran conjugates were determined after incubation at 37 degrees C in diluted luminal contents of the gastrointestinal (GI) trace of male Sprague-Dawley rats. The hemiesters were rapidly hydrolyzed in the proximal small intestine (e.g., dexamethasone-hemiglutarate t1/2 = 0.5 h). This rate decreased progressively down the GI tract (t1/2 = 4.8, 54, and 68 h in distal small intestine, cecum, and colon, respectively). The enzyme responsible for hemiester hydrolysis, apparently a type-A alkaline carboxylesterase, is probably of host origin because its activity is highest in the small intestine where bacterial count is low. The dextran conjugates resisted hydrolysis in upper GI tract contents but were rapidly degraded in cecal and colonic contents where the bacterial count is high. The dextran conjugate tested, methylprednisolone-succinate-dextran, was easily hydrolyzed by an endodextranase, indicating that substrate specificity is not lost upon the attachment of glucocorticoid. The results of this study indicate that dextran conjugates may be useful in selectively delivering glucocorticoids to the large intestine for the treatment of colitis.

Anaerobiosis↗

Application of selective extraction to the study of iron species present in diet and rat gastrointestinal tract contents.

Iron speciation in rodent diet and rat gastrointestinal tract lumen during dietary digestion and absorption was investigated with a novel selective extraction technique. Five Fe fractions were identified, namely exchangeable (soluble in 1 M-magnesium chloride), carbonate-bound (soluble in mild acid), oxide-bound (soluble in hydroxylamine-acetic acid), organic-bound (soluble after treatment with peroxide in nitric acid) and residual. Fe from the pelleted diet was mobilized by rat stomach to the exchangeable fraction, then redistributed to the carbonate- and oxide-bound fractions on passage through the proximal small intestine. In vitro incubation of diet with hydrochloric acid failed to mimic the in vivo effect of the stomach. In vitro neutralization of stomach contents with bicarbonate was found to produce a similar effect on Fe speciation to that seen when diet passed the proximal small intestine in vivo. Comparison of 59Fe speciation in extrinsically labelled diet with endogenous Fe speciation showed that extrinsic labelling does not uniformly label all endogenous species. The experiments suggest that selective extraction may provide a useful approach to the study of Fe species present in diets, in vitro digestions and gastrointestinal contents.

Animals↗

Comparative body compositions of the dog and goat.

The weights of certain organs and tissues of dogs and goats were measured and expressed as percentages of the total body weights. Species differences were observed in the contribution of several organs to the body weight. In the goat, a large percentage of the body weight was due to gastrointestinal contents. When calculations were made with the gastrointestinal contents eliminated from the body weight, many of the originally observed differences disappeared. After exclusion of the weight of gastrointestinal contents, only the values for skin, large intestine, and kidneys were significantly different between species. The possible influence of body composition on drug dosage is discussed.

Animals↗

Synthesis and properties of polysaccharide prodrugs of 5-aminosalicylic acid as potential colon-specific delivery systems.

The drug release of the polymer prodrugs of 5-aminosalicylic acid (5-ASA) was not only dependent on the property of the polymers but also dependent on the solubility of the prodrugs. We prepared several polysaccharide prodrugs of 5-ASA to examine the effect of solubility of prodrugs on the release characteristics of 5-ASA in the gastrointestinal contents of rats. The amide prodrug, chitosan-5-ASA (ChT-5-ASA), did not release the 5-ASA in the cecal and colonic contents. The ester prodrugs, hydroxypropyl cellulose-5-ASA (HPC-5-ASA), being poor solubility in 0.05mol/l acetic acid solution also did not release the 5-ASA in any of gastrointestinal contents of rats. Whereas the 5-ASA release from cyclodextrins-5-ASA (CyDs-5-ASA) in cecal and colonic contents was significantly higher than that in stomach and small intestine contents. And furthermore, with the decrease in the degree of substitution, the solubility of CyD-5-ASA increased, and the release of 5-ASA in the gastrointestinal contents was also higher at the same time interval of incubation. When the ratio of cyclodextrin (CyD) and 5-formylaminosalicylic acid (5-fASA), a precursor of 5-ASA prodrugs, was 1:10, CyD-5-ASA was very slightly soluble, and no release of 5-ASA was observed within 48h in gastrointestinal contents. The present results suggested that the ester prodrugs of 5-ASA with certain solubility could release 5-ASA in the cecal and colonic contents of rat.

Animals↗

Comparison of the water-holding capacity of wheat bran products prepared by wet and dry smashing methods in vitro and effect on the gastrointestinal retention time in rats in vivo.

Microfibril wheat bran (MFW) prepared by wet smashing of wheat bran using a colloidal mill has the advantages of being more palatable than other wheat bran and easier to apply to various foods. In this study, we investigated water-holding capacity (WHC) and physiological effects of a novel food material, MFW, focusing on shortening of the retention time of the gastrointestinal contents compared to those of dry smashing of wheat bran (DWB) prepared by conventional method, and wheat bran (WB), which is the raw materials. The mean particle size of MFW was 35 microns, and WHC was 5.1 g/g. In contrast, those of DWB were 61 microns and 3.0 g/g, respectively. Those of WB were 420 microns and 5.0 g/g, respectively. The WHC of MFW was 1.7 times greater than that of DWB and comparable to that of WB. The dietary fiber content in MFW, DWB, and WB were 73.5, 66.9 and 70.2%, respectively. Six-week-old Fisher rats were divided into three groups, and fed for 20 days with AIN-76 chow supplemented with MFW, DWB, or WB to a dietary fiber content of 10%. On days 14-16 of the experimental period, the mean retention time (MRT) of gastrointestinal content and fecal weight were measured using solid phase and liquid phase markers. On day 20 of the experimental period, animals were killed, and the water content, pH, composition of short chain fatty acids (SCFAs) in the cecal content and total amounts of SCFAs in the cecum were investigated. MRT in the MFW group was 15.2 +/- 0.8 h in the solid phase, which was significantly shorter than that in the DWB group (18.0 +/- 0.9 h) (p < 0.05), and comparable to that in the WB (15.5 +/- 2.4 h). MRT in the liquid phase was almost the same as that in the solid phase: 14.7 +/- 1.0, 18.4 +/- 0.8, and 16.0 +/- 2.5 h in the MFW, DWB, and WB groups, respectively. The fecal weight, pH, the concentration of SCFA in the cecal content and total amounts of SCFAs in the cecum did not differ among the groups, but the cecal water content was in the order of MFW > WB > DWB, showing a significant difference between each group (p < 0.05). The above finding suggested that MFW is a novel food material with a greater WHC and the ability of shortening the retention time of the gastrointestinal contents compared to DWB.

Animals↗

Distribution of ribonucleic acid coliphages in animals.

To determine the distribution pattern of ribonucleic acid (RNA) coliphages (classified by serological groups I through IV) in animal sources, we isolated RNA phages from (i) feces samples from domestic animals (cows, pigs, horses, and fowls), some other animals in a zoological garden, and humans, (ii) the gastrointestinal contents of cows and pigs, and (iii) sewage samples from treatment plants in slaughter houses. These samples were then analyzed serologically. The concentration of RNA phages in the first and second kinds of material was fairly low (10 to 10(3) plaque-forming units per original phage sample), whereas that in the third kind of material was fairly high (10(3) to 10(5) plaque-forming units per original phage sample). Concerning the group types of the RNA phages in the first and second kinds of material, human feces contained RNA phages of groups II and III almost equally, the gastrointestinal contents of pigs included those of groups I and II equally, and the feces or gastrointestinal contents of other mammals other than humans and pigs had those of group I exclusively. In the third type of material we found mostly group I phages with a minor fraction of group II phages. Thus, the prominent features of the distribution pattern of RNA phages are the predominance of groups III and II in humans and the predominance of group I in animals.

Animals↗

Defaecation and weight of the gastrointestinal tract contents after feed and water withdrawal in broilers.

1. Broilers were held under constant light for up to 24 h with access to feed and water, access to water only, or access to neither feed nor water. 2. Birds given continuous access to feed ate evenly over the 24-h period. Feed deprivation reduced drinking behaviour to about half of that when feed was available. Deprivation of feed, or of feed and water, had similar effects on defaecation and the reduction in the weight of the gut contents. It reduced the overall number of defaecations over the 24-h period to about 40% of that in birds given food and water, and the weight of the contents by about 75%. The maximum effect of deprivation on defaecation was seen after about 4 h, and on gut contents weight after about 12 h. 3. With longer fasting the contents of most parts of the gut, except the caeca, became wetter. 4. The findings may have implications for the practice of preslaughter food withdrawal to reduce the potential for soiling of the live birds and contamination of the carcase after slaughter. However, the likelihood is that relatively short overall feed deprivation times of not more than 8 to 12 h before killing may be desirable, but specifying firm recommendations on optimal feed withdrawal times requires further work.

Animals↗

[Quantitation of Ras p21 oncogene and DNA content of gastrointestinal smooth muscle tumors and prognostic significance].

Expression of ras p21 oncogene and DNA content of paraffin-embedded tissues from 55 smooth muscle tumors of the gastrointestinal tract were analysed simultaneously by using immunofluorescence and flow cytometry. All of 14 leiomyomas were found to be DNA diploid and lower-expression of ras p21. Four cases of DNA aneuploidy (33%) and 9 cases of ras p21 overexpression (75%) were found in 12 potential malignant smooth muscle tumors, while all 29 cases of leiomyosarcomas were aneuploidy (100%) (P < 0.005), but the rate of ras p21 overexpression was not increased continuously (72%) (P < 0.005). 24 of 33 aneuploid tumors (73%) were found to be ras p21 overexpression, while in 22 diploid tumors, there were only 6 cases (27%) (P < 0.005). The outcome of the patients with ras p21 lower-expressed diploid tumor was excellent, compared to the patients with ras p21 overexpressed aneuploid tumor it was worst (P < 0.005). It was suggested that DNA aneuploidy and ras p21 overexpression could be regarded as the mark of malignancy. The overexpression of ras p21 oncogene was always presented in the early stage of malignant smooth muscle tumors, when the cell proliferation was active but the DNA content was still normal, and stable in the whole procss of the tumor progression. ras p21 expression and DNA content could supply a deficiency each other in the diagnosis and could be used as objective parameters in distinguishing malignancy from benign and predicting the prognosis of the patients with smooth muscle tumors of the gastrointestinal tract.

Adolescent↗

Concentrations of heroin, 06-monoacetylmorphine, and morphine in a lethal case following an oral heroin overdose.

A case of lethal overdose by heroin ingestion is presented. The concentrations of drugs were measured several hours after death. Heroin, 06-monoacetylmorphine, and morphine were identified and quantitated in blood, urine, and gastrointestinal contents by gas chromatography-mass spectrometry and high-performance liquid chromatography. Concentrations of heroin, 06-monoacetylmorphine, and morphine were 109, 168, and 1140 ng/mL, respectively, in blood and 17, 12, and 425 ng/g, respectively, in gastrointestinal content. In urine, however, only morphine was detected at 3650 ng/mL.

Administration, Oral↗

Liquid chromatographic determination of olaquindox in medicated feeds and in contents of porcine gastrointestinal tract.

A liquid chromatographic method for the determination of olaquindox in both medicated feeds and porcine gastrointestinal tract is described. Samples are extracted with water and cleaned on a disposable reverse-phase column. The eluate is chromatographed on a reverse-phase column under isocratic conditions. Olaquindox is detected by UV absorption at 260 nm. The minimum amount detected by this method was 0.075 ng. The corresponding minimum detectable concentration in a 1 g sample was 0.3 mg/kg. The detector response was linear within the interval of 0-500 ng. Mean recovery of olaquindox in spiked gastrointestinal samples was 89 +/- 5% (mean +/- standard deviation, n = 43). Concentration profiles of olaquindox in the gastrointestinal tract of pigs fed medicated feed were used to evaluate the preventive potency against Treponema hyodysenteriae. The presence of some N-O reduced metabolites of olaquindox in the gastrointestinal tract was assessed.

Animal Feed↗