Search results for "Small Intestine"
showing 10 items of 94 documents
Evidence of a specialized transport mechanism for the intestinal absorption of baclofen
1989
Absorption of the spasmolytic drug baclofen in three selected intestinal segments of living anaesthetized rats in situ, is shown to be a specialized transport mechanism obeying Michaelis-Menten kinetics. Equation parameters were calculated through different procedures, whose features are discussed. A computer method based on the integrated form of Michaelis-Menten equation which reproduces the entire time course of drug absorption from the data found in three intestinal perfusion series at different initial concentrations, yielded Vm and Km values of 12.0 mg h-1 and 8.0 mg, respectively, in the mean segment of the small intestine, a rather selective absorption site for baclofen. Lesser but …
NK1- and NK3-receptor mediated inhibition of 5-hydroxytryptamine release from the vascularly perfused small intestine of the guinea-pig
1997
The effects of tachykinins on the spontaneous release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells into the portal circulation was investigated in vitro using the vascularly perfused isolated guinea-pig small intestine. 5-HT was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Substance P (SP) caused a concentration-dependent decrease in 5-HT outflow with an EC50 of 50 pmol/l. Similarly, the selective NK1 receptor agonist SP methyl ester (1 nmol/l) significantly inhibited 5-HT outflow (to 51 +/- 3%). When tetrodotoxin (1 mumol/l) was added to the arterial perfusion medium, the inhibition by SP of 5-HT outflow was not affected.…
Distribution of nitroreductive activity toward nilutamide in rat.
2004
Abstract Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO 2 ) antiandrogen used in the treatment of prostate carcinoma in man. Previously, we established that in the rat lung, the drug is metabolized into the corresponding hydroxylamine (R-NHOH) and amine (R-NH 2 ) derivatives. These results evidenced a cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the present studies, we extended the characterization of nilutamide metabolism in liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their respective luminal contents) of male Sprague–Dawley rats. Subcellular fractions for all tissues (except blood) examined (postmitochondrial, cy…
Kinetics of zinc transport in vitro in rat small intestine and colon: interaction with copper.
2002
The present study was planned to investigate the kinetic transport of zinc, in the intact intestine of the rat, in order to establish if more than one transporter is involved as well as the existence of a preferent sector in the cation uptake. Using an in vitro technique, the influx of zinc across the brush border membrane in three sectors of the small intestine (proximal, mid and distal) and in the colon of the rat was measured at six different concentrations (from 0.0007 to 11 mM). The kinetic study showed that intestinal transport of zinc occurs by a saturable process in the small intestine. The K(m) value obtained in the proximal segment (10.78+/-4.40 mM) is clearly higher than those ob…
Combination Therapy of Allopurinol and Dantrolene and Its Role In The Prevention of Experimental Ischemia Reperfusion Injury Of The Small Intestine.
2020
Background: The effect of different drugs on ischemia and reperfusion (I/R; induced oxygen free radical damage) was examined in small bowel tissue because the intestine is extremely sensitive to this pathology. Different drugs (allopurinol and dantrolene) can remove oxygen free radicals or inhibit the mechanisms leading to their generation, thus reducing mucosal lesions. We investigated the protective potential of combination therapy in the intestine against I/R damage. Methods: Forty-eight male Wistar rats were separated into 8 groups: one sham (control), one I/R (ischemia 60 min + reperfusion at 24 h), and 6 groups treated with allopurinol, dantrolene, or combination therapy. The grade of…
Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro
2011
Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of fla…
Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat …
2016
Abstract Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed…
Morphology and chronology of ischemic mucosal changes in the small intestine
1983
The morphology and chronology of an absolute ischemia was investigated on the small intestine of man and rat. It could be shown that the morphogenesis of ischemic damage to the intestinal mucosa in man does not differ from that in the rat. However, there are crucial and in therapeutic terms significant differences in the time course of the ischemic damage to the intestinal mucosa. Whereas in the small intestine of the rat, the first appreciable alterations - detachment and disruption of the lining epithelium at the villous tip - are already to be observed after absolute ischemia lasting 15 min, in the human small intestine the same lesions only occur after 4 h. A comparable complete necrosi…
Non-linear Intestinal Absorption Kinetics of Cefadroxil in the Rat
1989
Abstract Absorption of Cefadroxil in a selective intestinal absorption area (the proximal third of the small intestine) of the anaesthetized rat, at seven initial perfusion concentrations, ranging from 0·01 to 10·0 mg mL−1, is shown to be a non-linear transport mechanism. With the aid of computer-fitting procedures based on differential and integrated forms of Michaelis-Menten equation, Vm and Km values of 36·7–37·3 mg h−1 and 12·0–13·0 mg, respectively, were found. The statistical parameters were better than those obtained both for first-order and for combined Michaelis-Menten and first-order kinetics. There is no evidence for substantial passive diffusion processes. The results reported h…
Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues
2020
Metformin is the primary drug for type 2 diabetes treatment and a promising candidate for other disease treatment. It has significant deviations between individuals in therapy efficiency and pharmacokinetics, leading to the administration of an unnecessary overdose or an insufficient dose. There is a lack of data regarding the concentration-time profiles in various human tissues that limits the understanding of pharmacokinetics and hinders the development of precision therapies for individual patients. The physiologically based pharmacokinetic (PBPK) model developed in this study is based on humans’ known physiological parameters (blood flow, tissue volume, and others). The missing tissue-s…