In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Using the cytosensor microphysiometer to assess ocular toxicity.

Measuring in vitro cytotoxicity is one method currently used to estimate damage to the eye after chemical exposure. The Cytosensor Microphysiometer method evaluates cytotoxicity by measuring the test material-induced reduction in the metabolic rate of L929 cells. Changes in metabolic rate are measured indirectly as a function of changes in the extracellular acidification rate of the cells. During exposure to increasing concentrations of a cytotoxic material, there is a decrease in the release of acid byproducts into the surrounding medium as the cells die. These acidic metabolic byproducts cause a measurable change in the pH of a lightly buffered medium, which can be measured by the Cytosensor Microphysiometer. The change in the pH of the medium over time is then converted into a metabolic rate estimate for the cells. The endpoint measurement from the assay is the metabolic rate decline of 50%, the MRD50 value (in units of mg/ml).

Strain-related regional alterations of calcium-handling proteins in myocardial remodeling.

BACKGROUND: Cardiac remodeling has been shown to have deleterious effects at both the global and local levels. The objective of this study is to investigate the role of strain in the initiation of structural and functional changes of myocardial tissue and its relation to alteration of calcium-handling proteins during cardiac remodeling after myocardial infarction. METHODS: Sixteen sonomicrometry transducers were placed in the left ventricular free wall of 9 sheep to measure the regional strain in the infarct, adjacent, and remote myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks after infarction. Regional myocardial tissues were collected for calcium-handling proteins at the end study. RESULTS: At time of termination, end-systolic strains in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were measured to be -14.65 +/- 1.13, -5.11 +/- 0.60 (P < or = .05), and 0.92 +/- 0.56 (P < or = .05), respectively. The regional end-systolic strain correlated strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic reticulum Ca2+ adenosine triphosphatase subtype 2a (r2 = 0.68, P < or = .05) and phospholamban (r2 = 0.50, P < or = .05). A lesser degree of correlation was observed between the systolic strain and the abundance of sodium/calcium exchanger type 1 protein (r2 = 0.17, P < or = .05). CONCLUSIONS: Regional strain differences can be defined in the different myocardial regions during postinfarction cardiac remodeling. These differences in regional strain drive regionally distinct alterations in calcium-handling protein expression.