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At least 613 records · Page 34Linked to original sources
PubMed1997

Barrier function of reconstructed epidermis at the air-liquid interface: influence of dermal cells and extracellular components.

To evaluate the epidermal barrier function of in vitro reconstructed epidermis, we measured the penetration of estradiol and water across human keratinocytes cultured in defined medium (DM), in the presence of proliferative fibroblasts (pF) or conditioned medium derived from pF, at the air-liquid interface on synthetic porous membrane, noncoated or coated with laminin, fibronectin, type I collagen or type IV collagen. Ultrastructural analysis showed a well-developed stratum corneum whatever the culture conditions. The permeability of reconstructed epidermis in DM on a noncoated porous membrane was 5- to 10-fold higher than human native epidermis, with both tracers. No significant change in barrier function was observed whatever the culture conditions.

Cell Differentiation↗
PubMed2002

Dialogue and collaboration: a personal view on laboratory animal welfare developments in general, and on ECVAM's first decade in particular.

A personal view is presented on progress made during the last 25 years in applying the Three Rs (reduction, refinement, replacement) to animal testing in regulatory toxicology, with an emphasis on "good moments" (for example, international workshops on the principles and practical application of the validation process and on regulatory acceptance) and "not-so-good moments" (for example, the time taken to accept alternatives to the LD50 test and to accept in vitro tests for skin absorption as OECD Test Guidelines). The importance of dialogue and cooperation between international coordinating centres and scientific activities at the national level is stressed, as exemplified by the work of ECVAM during its first decade.

Animal Testing Alternatives↗
PubMed1987

Summary review of the health effects associated with phenol.

Phenol, a monohydroxy derivative of benzene, occurs naturally in animal waste and by decomposition of organic wastes. It is also produced by man, originally by fractional distillation of coal tar, but more recently by cumene hydroperoxidation and toluene oxidation. As a result of large production volume and natural sources, occupational and environmental exposure to phenol is likely. Phenol poisoning can occur by skin absorption, vapor inhalation, or ingestion, and, regardless of route of exposure, can result in detrimental health effects. Acute toxicity has been observed in man and experimental animals, resulting in muscle weakness, convulsions, and coma. In addition, studies have shown that although teratogenic effects have not been associated with exposure to phenol by either inhalation or oral route, high doses of phenol are fetotoxic. This paper addresses these studies and others in an attempt to determine if human health is at risk to those levels of phenol present in the environment and workplace. However, because data are limited, further research is necessary to analyze the mutagenic and carcinogenic potential of this chemical.

Animals↗
PubMed2002

PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol.

BACKGROUND: A "physiologically based pharmacokinetic" (PBPK) approach uses a realistic model of the animal to describe the pharmacokinetics. Previous PBPKs have been designed for specific solutes, required specification of a large number of parameters and have not been designed for general use. METHODS: This new PBPK program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that the user input is minimized. It has a simple user interface, graphical output and many new features: 1) An option that uses the measured plasma concentrations to solve for the time course of the gastrointestinal, intramuscular, intraperotineal or skin absorption and systemic availability of a drug - for a general non-linear system. 2) Capillary permeability limitation defined in terms of the permeability-surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung model that includes perfusion-ventilation mismatch. 6) A general optimization routine using either a global (simulated annealing) or local (Powell) minimization applicable to all model parameters. RESULTS: PKQuest was applied to measurements of human propranolol pharmacokinetics and intestinal absorption. A meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases liver metabolism by 20%. There is a significant delay in the oval propranolol absorption in fasting subjects that is absent in fed subjects. The oral absorption of the long acting form of propranolol continues for a period of more than 24 hours. CONCLUSIONS: PKQuest provides a new general purpose, easy to use, freely distributed www.pkquest.com and physiologically rigorous PBPK software routine.

Absorption↗