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At least 127 records · Page 7Linked to original sources
PubMed2001

The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling.

Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To analyze the relationship between the pharmacokinetics of glycyrrhizic acid in its toxicity, the kinetics of glycyrrhizic acid and its biologically active metabolite glycyrrhetic acid were evaluated. Glycyrrhizic acid is mainly absorbed after presystemic hydrolysis as glycyrrhetic acid. Because glycyrrhetic acid is a 200-1000 times more potent inhibitor of 11-beta-hydroxysteroid dehydrogenase compared to glycyrrhizic acid, the kinetics of glycyrrhetic acid are relevant in a toxicological perspective. Once absorbed, glycyrrhetic acid is transported, mainly taken up into the liver by capacity-limited carriers, where it is metabolized into glucuronide and sulfate conjugates. These conjugates are transported efficiently into the bile. After outflow of the bile into the duodenum, the conjugates are hydrolyzed to glycyrrhetic acid by commensal bacteria; glycyrrhetic acid is subsequently reabsorbed, causing a pronounced delay in the terminal plasma clearance. Physiologically based pharmacokinetic modeling indicated that, in humans, the transit rate of gastrointestinal contents through the small and large intestines predominantly determines to what extent glycyrrhetic acid conjugates will be reabsorbed. This parameter, which can be estimated noninvasively, may serve as a useful risk estimator for glycyrrhizic-acid-induced adverse effects, because in subjects with prolonged gastrointestinal transit times, glycyrrhetic acid might accumulate after repeated intake.

Administration, Topical↗
PubMed1990

[Causes, sequelae and possible ways of preventing hypophosphatemia in patients with cerebral ischemia].

Hypophosphatemia revealed in patients with acute disorders of cerebral circulation was one of the causes of a decrease of the content of 2,3-DPG, ATP in red blood cells and of a reduction of Ca2(+)-ATPase activity in red blood cell membranes. In the given group of patients, hypophosphatemia was provoked by complete parenteral feeding, hypocapnia and by loss of phosphorus with urine and congestive gastrointestinal contents.

2,3-Diphosphoglycerate↗
PubMed1997

Plastinated canine gastrointestinal tracts used to facilitate teaching of endoscopic technique and anatomy.

Plastinated specimens, when prepared with a design for endoscopic use, can serve as a practical model for teaching. Intact alimentary canals were excised from fresh canine cadayers. Cannulas in excess of the intended endoscope size (9.6 mm diameter) were placed in restrictive openings [cardiac ostium (ostium cardiacum), pyloric ostium (ostium pyloricum) and cecocolic orifice (ostium cecocolicum)]. These cannulas allowed ingesta to be removed and maintained adequate diameters for endoscoping. After flushing out the gastrointestinal contents, specimens were formaldehyde-fixed overnight in a dilated anatomical conformation. Prior to S10/S3 impregnation, fixative was flushed from the specimens and they were dehydrated in acetone. After impregnation, slow cure (elongation of S3 molecules at room temperature) was allowed to proceed for approximately 1 week. The gastrointestinal tracts were maintained in a dilated conformation by a positive pressure air flow. When polymer seepage was minimal, they were cured using small quantities of S6 (final curing agent). The curing agent was contained around the specimen by enclosing the specimens in plastic bags. The plastinated specimens retain their dilated anatomical conformation, and may be used to teach both endoscopic technique and gastrointestinal anatomy.

Anatomy↗
PubMed2001

The effects of overnight fasting, feeding, or sucrose supplementation prior to necropsy in rats.

This study was designed to investigate the acute effects on routine hematology, serum biochemistry, gastrointestinal contents and weight, and liver weight and morphology due to overnight sucrose feeding of rats prior to necropsy. Groups of rats (five males and five females/group) were fasted overnight, fed chow, or fed sucrose and were euthanized approximately 17 h later. At necropsy, blood was obtained for hematology and serum biochemistry profiling, and the livers and gastrointestinal tracts were weighed and examined. The livers also were evaluated microscopically. The blood glucose and urea nitrogen concentrations and liver weights of animals fed sucrose differed significantly from those of the other groups. Alterations were more striking in males than females. Marked histological changes were present in livers from animals fed sucrose prior to necropsy compared with fasted or chow-fed animals, and these changes were attributed to increased glycogen deposition in the sucrose-fed animals. Because of alterations in hepatic structure and function, we cannot recommend the practice of feeding sucrose to rats prior to necropsy for toxicology studies or any studies examining hepatic function.

Animals↗
PubMed1976

[Absorption, distribution, excretion and metabolism of a basic ether compound (R97) with antispasmodic activity].

The absorption, distribution, excretion and metabolism of 14C labelled 2-chlorophenyl-1-phenyl-3-(2 methyl-piperidino) propyl ether methyl iodide (14C-R97) were studied by means of direct measurement of radioactivity and autoradiographic technique in rats. 1) With intravenous administration, radioactivity was found in all the tissues and organs immediately after dosing, with particularly high levels in the liver, kidney, heart and lung. Five minutes after administration, the level of radioactivity in blood decreased to about 6% of the initial level, indicating the rapid absorption of radioactive material by other tissues and organs. Radioactivity was not detected in the brain and eye. Thirty minutes after administration, the concentration of radioactivity in the gastrointestinal contents was very high and a certain amount of radioactivity uptake was noted both in gastric and intestinal mucosa. Approximately 12% and 40% of radioactivity administered was excreted in the urine and feces respectively during the first 24 hours, however, the excretion of radioactivity by expiration was not determined. 2) With oral administration, radioactivity was restricted to the gastrointestinal tract. Activities in other tissues and organs were not detectable. Approximately 94% of the radioactivity administered was recovered in feces during the first 24 hours. 3) Radioactivity was not observed in either the foetus or placenta after both intravenous and oral administrations. 4) The results from autoradiographic study were in good accord with those described above.

Animals↗
PubMed1980

Effects of gastrointestinal polypeptides on hormone content of endocrine pancreas in the rat.

Although trophic actions of gastrointestinal peptides on exocrine pancreas have been shown, little is known regarding their effects in endocrine pancreas. Therefore, we measured the contents of somatostatin-like immunoreactivity (SLI), insulin and glucagon, in pancreatic extracts from rats that had been treated three times a day for 10 days with saline; 1 microgram/kg caerulein; 5, 25, and 100 microgram/kg secretin; 1 microgram/kg caerulein plus 5, 25, and 100 microgram/kg secretin; 25 microgram/kg pancreatic polypeptide; 15 microgram/kg glicentin; or 15 microgram/kg gastric-inhibitory polypeptide. Pancreatic SLI content was significantly increased in rats treated with glicentin and caerulein plus secretin at the two higher doses. No difference was noted between the control and the caerulein plus 100 microgram/kg secretin groups in delta-cell number per islet when examined by the immunoperoxidase technique. These data suggest that because of their effect on SLI content gastrointestinal polypeptides may modulate pancreatic endocrine function.

Animals↗
PubMed1990

Gastrointestinal disease and oral contraception.

Oral contraceptive steroids play a major role in modern family planning. With the present tendency to decrease the doses of both estrogens and progestogens, any factor that reduces the bioavailability of the lower-dose preparations may have an impact on contraceptive protection. Although ethinyl estradiol, the most commonly used oral estrogen, is liable to an enterohepatic circulation as unchanged drug, the commonly used progestogens are not. At present, no convincing evidence exists in the human subject that disruption of the enterohepatic circulation by antibiotics or antacids does reduce contraceptive efficacy of the pill. Oral contraceptive steroids are mainly absorbed from the small bowel, and contraceptive efficacy depends on its absorptive capacity. Enhanced passage of gastrointestinal contents or impaired absorption may thus contribute to contraceptive failures in patients who have chronic inflammatory disease, diarrhea, ileostomy, or jejunoileal bypass.

Antacids↗
PubMed1981

Effect of rate of catabolism of DL-[1-14C]lysine on estimation of whole body protein synthesis in rats.

We investigated the effect of rate of DL-[1-14C]lysine metabolism on the estimation of whole body protein synthesis in rats. Growing rats were given single injections of DL-[1-14C]lysine via a tail vein and cumulative expiration of 14CO2 was measured after 3, 6 and 9 hours. Total 14C in protein-bound lysine, body lipids, perchloric acid-soluble material, urine, feces and gastrointestinal contents was recovered after 9 hours. After correcting for radiochemical purity and stereoisomerism of DL-[1-14C]lysine, 95.1% of injected L-[1-14C]lysine was found in expired air and protein-bound [14C]lysine. Daily nitrogen retention of rats was 150 mg and daily incorporation of lysine into body protein was 119% of that absorbed from the gastrointestinal tract, from which rates of whole body protein synthesis, accretion and degradation were estimated to be 2.58, 0.76 and 1.83 g/day, respectively. Expressed per unit of body weight the rate of protein synthesis was not significantly different from previous estimates using L-[1-14C]leucine, which indicated that differences in catabolic pathways of leucine and lysine as well as differences in intracellular specific activities of these [14C]amino acids had a negligible effect on the estimation of protein synthesis.

Animals↗
PubMed2003

Meningitis following gunshot wound of the neck.

It is generally assumed that a missile fired from a gun is subjected to sufficient heat to render it sterilized. For this reason, retained bullets are not usually considered a source of infection. The infectious complications associated with gunshot wounds are typically attributed to perforation of a hollow viscus with leakage of gastrointestinal contents causing peritonitis or intra-abdominal abscess. There are several reports of bacterial meningitis involving the spinal cord in gunshot wounds that perforate the intestine prior to involving the thoracic or lumbar vertebral column; however, there are no published reports of cerebral meningitis resulting from a retained projectile in the spinal canal in which there was no injury to the gastrointestinal tract. This manuscript describes a woman who died as a result of unsuspected acute bacterial meningitis which developed secondary to a gunshot wound of the neck. The projectile fractured the first thoracic vertebra, lacerated the dura and contused the spinal cord at the C7-T1 junction. Meningitis developed at the C7-T1 level and ascended along the cervical spinal cord to the brain. The infection caused acute neurologic deterioration and death four days following the initial injury.

Adult↗
PubMedDate not supplied

Role of gut contents, intestinal wall, and liver on the first pass metabolism and absolute bioavailability of isotretinoin in the dog.

The absolute bioavailability and first pass metabolism of isotretinoin by the gut contents, gut wall, and liver of the dog were assessed with a sensitive and specific high performance liquid chromatographic analytical method and a recently published pharmacokinetic model. [12C]- and [14C]isotretinoin were simultaneously administered to the dog by iv and oral routes, respectively. Blood samples were obtained from the jugular and the portal veins at specified times to quantify [12C]isotretinoin and [14C]isotretinoin blood concentrations. In addition, blood, bile, urine, and the gastrointestinal contents were analyzed for carbon-14-containing materials. The harmonic mean elimination half-life (t 1/2 beta) for the simultaneous iv and oral administration was approximately 5.5 hr. The mean +/- SD blood clearance (ClB) following iv administration and the intrinsic clearance following oral administration were 5.19 +/- 2.40 and 6.63 +/- 3.72 ml/min/kg, respectively. The average absolute bioavailability was 21%, indicating an overall first pass effect of approximately 80%. The majority (approximately 72%) of the first pass effect occurred in the gut lumen with the gut wall and liver making a lesser contribution to the overall first pass effect. These results demonstrated that the low absolute bioavailability was largely due to loss of drug prior to reaching the portal circulation; and analysis of gut contents for total carbon-14 activity suggested that a fraction of isotretinoin dose was biologically or chemically degraded in the gut lumen prior to absorption.

Animals↗
PubMed1997

Experimental Escherichia coli O157:H7 carriage in calves.

Nine weaned calves (6 to 8 weeks of age) were given 10(10) CFU of a five-strain mixture of enterohemorrhagic Escherichia coli O157:H7 by oral-gastric intubation. After an initial brief period of pyrexia in three calves and transient mild diarrhea in five calves, calves were clinically normal throughout the 13- to 27-day study. The population of E. coli O157:H7 in the faces decreased dramatically in all calves during the first 2 weeks after inoculation. Thereafter, small populations of E. coli O157:H7 persisted in all calves, where they were detected intermittently in the feces and rumen contents. While withholding food increased fecal shedding of E. coli O157:H7 by 1 to 2 log10/g in three of four calves previously shedding small populations of E. coli O157:H7, the effect of fasting on fecal shedding of E. coli O157:H7 was variable in calves shedding larger populations. At necropsy, E. coli O157:H7 was not isolated from sites outside the alimentary tract. E. coli O157:H7 was isolated from the forestomach or colon of all calves at necropsy. Greater numbers of E. coli O157:H7 were present in the gastrointestinal contents than in the corresponding mucosal sections, and there was no histologic or immunohistochemical evidence of E. coli O157:H7 adhering to the mucosa. In conclusion, under these experimental conditions, E. coli O157:H7 is not pathogenic in weaned calves, and while it does not appear to colonize mucosal surfaces for extended periods, E. coli O157:H7 persists in the contents of the rumen and colon as a source for fecal shedding.

Animals↗
PubMed2001

Wetting behavior of bile salt-lipid dispersions and dissolution media patterned after intestinal fluids.

The wetting properties of bile salt-lipid solutions and dispersions patterned after the contents of the upper intestine in the fed and fasted states were evaluated using poly(methyl methacrylate) (PMMA) as a model substrate. The surface tension of the solutions and their contact angles on PMMA were measured. Media compositions for the intestinal fed and fasted states were estimated on the basis of physiologic data. The effect of various individual lipids and media composition was also evaluated relative to the adhesional, immersional, and spreading stages of wetting. In micellar systems, both the type and concentration of lipid present in the bile salt solution had an influence on wetting. The wetting of media patterned after gastrointestinal contents showed marked differences with respect to the fed or fasted state compositions. For the fed state compositions, alteration of the solution pH from 7.5 to 5.0 resulted in a significant change in wetting. The surface tension of the medium representative of the fasted state was 15 mN/m higher than that of the fed state. The wetting properties of the physiologically representative media formulated in this study were markedly different compared with other media proposed in the literature. Analysis of the wetting behavior of individual lipids as a function of concentration in bile salt solutions showed that they adsorb in a manner that progressively reduces the expected wetting of the surface. The results have implications for the design and formulation of both biorelevant and surfactant-based dissolution media.

Animals↗
PubMed1980

Gastrointestinal osmolality electrolyte and organic acid composition in five species of East African herbivorous mammals.

inherent differences observed in ionic composition of gastrointestinal contents due to diet, feeding regimen and (or) site along the length of the digestive tract were controlled so that a clearer understanding of species differences could be obtained. Three species of ruminants (i.e., Zebu cattle, sheep and goat), a pseudo-ruminant (camel) and a nonruminant (donkey) were compared. Specific differences were observed in organic acid concentration, pH and electrolyte composition at various sites along the length of the tract. In general, Zebu cattle exhibited major differences in colonic volatile fatty acid, sodium and chloried concentrations when compared to other species. Donkeys, camels, sheep and goates were generally similar in their gastrointestinal ionic composition.

Animals↗
PubMed1999

Studies on the antidiarrhoeal properties of pentaclethra macrophylla leaf extracts.

The aqueous (WE) and ethanol (EE) leaf extracts of Pentaclethra macrophylla were tested for antidiarrhoeal activity using experimental animal models. The i.p. LD50 values were established to be 770 mg/kg and 280 mg/kg for the aqueous (WE) and ethanol (EE) extracts, respectively. Antidiarrhoeal potential of the extracts was evidenced by a significant reduction in faecal output and protection from castor oil-induced diarrhoea in rats treated with the extracts. In addition the extracts significantly (p < 0.05) decreased propulsive movement of gastrointestinal contents in mice. On isolated tissue preparations, the extracts significantly reduced in a non-specific manner contractions evoked by acetylcholine, nicotine and histamine. The extracts inhibited the growth of common pathogenic microorganisms. The antispasmodic as well as the antimicrobial effects of the extracts may explain the rationale for the use of the plant in traditional medicine as a popular antidiarrhoeal recipe.

Animals↗
PubMed2003

Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor.

Functional gamma-secretase inhibitors (FGSIs) can block the cleavage of several transmembrane proteins including amyloid precursor protein (APP), and the cell fate regulator Notch-1. FGSIs, by inhibiting APP processing, block the generation of amyloid beta (Abeta) peptides and may slow the development of Alzheimer's disease. FGSIs used to inhibit APP processing may disrupt Notch processing, thus interfering with cell fate determination. Described herein is a FGSI-mediated gastrointestinal toxicity characterized by cell population changes in the ileum of rats, which are indicative of Notch signaling disruption. Microarray analysis of ileum from FGSI-treated rats revealed differential expression responses in a number of genes indicative of Notch signaling perturbation, including the serine protease adipsin. We were able to show that FGSI-treated rats had elevated levels of adipsin protein in gastrointestinal contents and feces, and by immunohistochemistry demonstrated that adipsin containing ileum crypt cells were increased in FGSI-treated rats. The mouse Adipsin proximal promoter contains a putative binding site for the Notch-induced transcriptional regulator Hes-1, which we demonstrate is able to bind Hes-1. Additional studies in 3T3-L1 preadipocytes demonstrate that this FGSI inhibits Hes-1 expression while up-regulating adipsin expression. Overexpression of Hes-1 was able to down-regulate adipsin expression and block pre-adipocyte differentiation. We propose that adipsin is a Hes-1-regulated gene that is de-repressed during FGSI-mediated disruption of Notch/Hes-1 signaling. Additionally, the aberrant expression of adipsin, and its presence in feces may serve as a noninvasive biomarker of gastrointestinal toxicity associated with perturbed Notch signaling.

3T3-L1 Cells↗
PubMed1998

Small intestinal transit and digestibility of lactitol in Wistar rats.

The study was conducted to evaluate if the recovery of lactitol and its cleavage products varied when different doses of this disaccharide sugar alcohol (150 and 1,200 mg/kg body weight, respectively) were given by gastric gavage to unadapted male rats. Phenol red added to the test solution as marker dye served to determine the intestinal transit and distribution areas. Marker transit revealed that the test substance did not reach the cecum in all series. Gastric emptying was more retarded after the high dose. Administration of low doses did not alter intestinal transit and luminal volume as compared to control animals. But a much larger luminal volume was found in the third intestinal quarter after the high doses, although the marker transit through this segment was equal under all experimental conditions. The total gastrointestinal recovery of lactitol at 63.2 (+/- 3.9) and 75.5 (+/- 4.5)% was significantly different (p < 0.001) 1 hour after administration of 150 mg and 1200 mg/kg body weight, respectively. Only free sorbitol was detected in the gastrointestinal contents in both dosage groups. Based on these results and correcting the values for marker recovery (85% in both groups), it is reasonable to assume that the maximum amount of lactitol that can be hydrolyzed and absorbed by the small intestine is 11.2 and 25.2%, respectively, and not zero. In conclusion, the caloric availability of lactitol is dose-dependent and should be determined under normal conditions in which the laxative threshold is not exceeded.

Animals↗
PubMed1992

Gastrointestinal transit and digestibility of maltitol, sucrose and sorbitol in rats: a multicompartmental model and recovery study.

Using data obtained with a dye marker and the gavage technique, the kinetics of gastrointestinal transit of different loads of sugar substitutes (maltitol, sorbitol) and sugar (sucrose) in the rat were analysed using a linear multicompartmental model over a range from the realistic to the non-physiologic high, of carbohydrate intake levels and using only a few experimental time points. The model gave detailed insight into intestinal propulsion and gastrocecal transit time. Rate constants of transport between the compartments investigated were determined; they showed characteristics which could be related to the substance and the dosage administered. Analyses of the gastrointestinal content and calculations of the intestinal net water movement showed that the digestibility and absorption of the disaccharide sugar alcohol, maltitol, in the small gut depended inversely on the dose ingested. For all substances tested, caloric availability in the small intestine was calculated. At a physiological low level of maltitol intake, the results also indicated an insignificant calorie-saving effect in comparison to sucrose, an effect based mainly on the slow absorption rate of the maltitol cleavage product sorbitol.

Animals↗
PubMed1976

[Reflux esophagitis (author's transl)].

The term "Refluxdisease" consider an esophageal response (either subjective or objective) to injury caused by gastrointestinal contents. Thickening of the basal layer of the esophageal mucosa, reflux esophagitis, endobrachyesophagus, acquired short esophagus and peptic stenosis are different stages of the objective esophageal response. The diagnosis of reflux disease must take account of these findings where appropriated. The various stages of reflux disease can only by recognized and adequately treated following an exact diagnosis that takes into account as may parameters as possible. For this reason fundoplication, which is at present the most effective procedure, should only be performed when the indications are particularly strong.

Esophageal Stenosis↗