Search results for "Intestinal"
showing 10 items of 2024 documents
Kinetics of the intestinal uptake of zinc acexamate in normal and zinc-depleted rats.
1990
Abstract The uptake of zinc as acexamic acid salt in the small intestine of the anaesthetized rat was shown to be a two-phase process in normal animals. The first phase is rapid mucosal binding which satisfies the Freundlich isotherm equation and which involves about 30 per cent of the initially perfused zinc. The second phase was characterized as an apparent absorption step which obeys Michaelis-Menten and first-order combined kinetics, with the following parameters: Vm = 6.51 mg h−1; Km = 2.96 mg; ka = 0.306 h−1. In largely non-saturated conditions, an apparent global rate constant of about 2.50 h−1 was calculated. No significant interference due to endogenous zinc excretion into the smal…
Intestinal absorption pathway of gamma-aminobutyric acid in rat small intestine.
1994
Intestinal absorption of gamma-aminobutyric acid (GABA), as a model compound for gamma-aminoacids, has not been extensively studied from the kinetic viewpoint. Since data from our laboratory suggested that some competition arises between intestinal absorption of beta-alanine and GABA and since our intent was to maintain the aqueous stagnant diffusion layer in order to approach absorption tests to in vivo physiological conditions, a rat jejunum in situ study was undertaken in order to gain an insight into the mechanism of GABA absorption. In the present paper, results from assays using isotonic perfusion solutions with starting GABA concentrations ranging from 1 to 50 mM are reported. They s…
Quantitative analysis of the effect of controlled-release formulation on nonlinear gastrointestinal absorption of P-glycoprotein substrate talinolol …
2020
Abstract Oral absorption of talinolol, a substrate of P-glycoprotein (P-gp), from a sustained-release (SR) formulation was reportedly decreased compared to that from an immediate-release (IR) formulation. The aim of this study was to predict and understand the effect of controlled-release formulation on the oral absorption of P-gp substrates by developing a physiologically based pharmacokinetic (PBPK) absorption model incorporating multiple kinetic parameters obtained from in vitro studies, using talinolol as a model substrate. Simulation analysis using the developed PBPK absorption model indicated that the clinically observed marked decrease in the plasma concentration of talinolol adminis…
Effect of simulated gastrointestinal digestion on plant sterols and their oxides in enriched beverages
2013
Abstract This study evaluates the bioaccessibility (percentage of soluble compound available for absorption) of plant sterols (PS) and their oxides (phytosterol oxidation products, POPs) after simulated gastrointestinal digestion in fruit (Fb), milk (M) and fruit-based milk beverages with (FbM a ) or without (FbM b ) tangerine juice. In beverages and their bioaccessible fraction (BF), campesterol, campestanol, stigmasterol, β-sitosterol and sitostanol were detected. Bioaccessibility of total PS ranged between 2.62 and 6.48%, FbM b yielding the highest value, followed by FbM a > Fb > M. Campesterol/campestanol were the most bioaccessible PS. Only oxides of β-sitosterol were detected in beve…
Evidence of competitive inhibition for the intestinal absorption of baclofen by phenylalanine
1996
Abstract Previous studies showed that the absorption of the antispastic drug baclofen, in the rat middle intestine, is inhibited by β-alanine, γ-aminobutyric acid (GABA) and leucine. It was concluded that baclofen intestinal transport was mediated, at least in part, by the β-, γ- and α-amino acid carriers. We therefore focused our next studies on the analysis of the possible inhibition of drug absorption by an aromatic α-amino acid model compound, phenylalanine. An in situ study in the rat small intestine was undertaken in order to evaluate the effect of phenylalanine on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen w…
Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
2021
Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB). Previous computer simulation data indicate increased metformin absorption after RYGB. In this study, we experimentally determined the region-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then imp…
Absorption of Drugs after Oral Administration
2007
After oral administration, drugs must be absorbed through the gastrointestinal tract to achieve the systemic circulation and exert their pharmacological effects. The successful formulation of an optimized oral drug delivery system requires a detailed consideration and a good understanding of the intestinal absorption process, its possibilities and limitations. This article gives an overview and update on the concepts, possibilities, and limitations of drug absorption after oral administration. Keywords: oral administration; drug absorption; oral drug delivery system; gastrointestinal tract; intestinal absorption
WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas
2021
Abstract Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described. We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas. To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization…
Mitochondrial D310 mutations in colorectal adenomas: an early but not causative genetic event during colorectal carcinogenesis.
2008
Somatic mutations of the D310 sequence of the mitochondrial DNA are reported in human cancers, including colorectal cancers (CRC). The presence of these mutations at early or late steps of colorectal carcinogenesis is unknown. Their prevalence increased significantly with the number of cytosines in the D310 sequence of the matched normal tissue (D310 polymorphism), suggesting that this polymorphism could be a risk factor for CRC. The aim of this study was (i) to investigate the prevalence of D310 mutations in 64 colorectal adenomas and 36 liver metastases from 15 CRC patients, (ii) to assess the relation between D310 polymorphism and the risk of colorectal adenoma in a case-control study in…
Three-dimensional analysis of tumour vascular corrosion casts using stereoimaging and micro-computed tomography
2009
Objective: In order to perform effective translational research for cancer therapy, we need to employ preclinical models which reflect the clinical situation. The purpose of this study was to quantitatively compare the vascular architecture of human colorectal cancer and experimental tumour models to determine the suitability of animal models for vascular studies and antivascular therapy.Methods: In this study we investigated the three-dimensional properties of colonic tumour vasculature in both human clinical tissues (normal mucosa control [n = 20], carcinoma [n = 20] and adenoma In = 61) and murine colorectal xenografts (LS147T [n = 6] and SW1222 [n = 6]). Scanning Electron Microscope Ste…