Search results for "Lability"

An automatic flow-through system for exploration of the human bioaccessibility of endocrine disrupting compounds from microplastics

2021

This article reports on the first attempt towards investigating the leaching rates in the human gastrointestinal (GI) tract of plastic-borne contaminants that can be ingested accidentally using physiologically relevant body fluids. Oral bioaccessibility under fasted and fed states was determined in dynamic mode exploiting an automatic flow setup. The flow system is able to mimic the fast uptake of the released species from the polymeric matrix by absorption in the human digestive system by the in-line removal of the leached species. Complex GI extractants based on the Unified Bioaccessibility Method (UBM, fasted state) and Versantvoort test (fed-state) were brought through a microplastic-lo…

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Moxifloxacin Hydrochloride.

2020

Abstract In this monograph, literature data is reviewed to evaluate the feasibility of waiving in vivo bioequivalence testing and instead applying the Biopharmaceutics Classification System (BCS) based methods to the approval of immediate-release solid oral dosage forms containing moxifloxacin hydrochloride as the sole active pharmaceutical ingredient. To facilitate the feasibility decision, solubility and permeability and dissolution characteristics in the context of the BCS, therapeutic index, therapeutic use, pharmacokinetic parameters, bioequivalence/bioavailability issues, drug-excipient interactions and other relevant data were taken into consideration. Moxifloxacin is a BCS class I d…

Cluster-determinant 36 (CD36) impacts on vitamin E postprandial response

2014

International audience; Scope: A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma alpha-tocopherol concentration, suggesting a possible role of this protein in vitamin E intestinal absorption or tissue uptake. Methods and results: To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on alpha- and gamma-tocopherol transmembrane uptake and efflux using transfected HEK cells. gamma-Tocopherol postprandial response was then assessed in CD36-deficient mice compared with wild-type mice, after the mice had been fully characterized for their alpha -tocopherol, vitamin A and lipid plasma,…

PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery

2013

Abstract Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}- d , l -aspartamide (PHEA-IB-p(MANa + )), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa + ) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa + ) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copol…

Calcium bioavailability in human milk, cow milk and infant formulas—comparison between dialysis and solubility methods

1999

Abstract The percentages of total, soluble and dialysable calcium of human milk, cow milk and milk and soy based infant formulas were determined in order to detect possible differences in the calcium bioavailability of the samples. For this purpose an in vitro method was applied to these four calcium sources. The ranking of the analysed samples in terms of calcium bioavailability depends on the criteria applied. Calcium ranked dialysis percentage was: cow milk>human milk>soy based formula>milk based formulas. Calcium ranked solubility percentage was: human milk>cow milk>soy-based formula>milk-based formulas. Comparison of the results of the in vitro assay with the information available on i…

Calibration and Validation

2016

The aim of this chapter is to summarise the problems incurred during the phases of calibrating and validating the extortion racket models used by the GLODERS project. The chapter starts with the discussion of the data availability and summarises shortly the contents of Sect. 4.3. It continues with a discussion of what parameterisation, calibration, sensitivity analysis and validation have to do with each other and ends up with a discussion of the validity of the GLODERS models.

Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents

2011

Cancers are the largest cause of mortality and morbidity in industrialized countries. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects such as the modulation of innate immune cells and adaptive immune cells that could infiltrate the tumor. In the tumor microenvironment, there is a delicate balance between antitumor immunity and tumor-originated proinflammatory activity, which weaken antitumor immunity. Consequently; modulation of immune cells and inflammatory processes represent attractive targets for therapeutic intervention in malignant diseases with the goal to restore the sensiti…

P105. New findings on vasodilator potency, tachyphylaxis, and bioavailability of organic nitrates reveal: The tolerance-devoid clinical action of pen…

2006

Dose Responsive Effects of Subcutaneous Pentosan Polysulfate Injection in Mucopolysaccharidosis Type VI Rats and Comparison to Oral Treatment

2014

Background We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (s.c.) injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. Methodology/principal findings One-month-old MPS VI rats were given once weekly s.c. injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED)), or daily oral PPS (4 mg/kg HED) for 6 months. Serum inflammato…

An approach to As(III) and As(V) bioavailability studies with Caco-2 cells

2005

Foods and drinking water are the main sources of human exposure to inorganic arsenic [As(III) and As(V)]. After oral ingestion, the intestinal epithelium is the first barrier to absorption of these species. A human intestinal cell line (Caco-2) was used to evaluate cell retention and transport of As(III) (15.6-156.0 microM) and/or As(V) (15.4-170.6 microM). Cell monolayer integrity, cell viability, membrane damage and effects on cell metabolism were evaluated. Only the highest concentrations assayed [As(III): 156.0 microM; As(V): 170.6 microM] produced a cytotoxic effect with different cellular targets: As(III) altered the permeability of tight junctions, and As(V) caused uncoupling of the …