Thomas Foster | PubMed Health

PubMed2006

Environmental enrichment decreases the afterhyperpolarization in senescent rats.

Previous research indicates that an age-related increase in the amplitude of the Ca2+-dependent, K+-mediated afterhyperpolarization (AHP) is related to cognitive decline. However, because the AHP is measured following completion of training, it is unclear whether the AHP amplitude is strictly dependent on biological aging or is modified by the training procedure. To address this distinction we examined the effect of environmental enrichment on the AHP amplitude. Young (5-8 months) and aged (22-24 months) male Fischer 344 rats were exposed to environmental enrichment conditions (EC) or maintained in individual cages (IC). Following 8-10 weeks of differential experience, sharp microelectrode current-clamp recordings were obtained in CA1 pyramidal neurons in hippocampal slices. Examination of the AHP demonstrated that the amplitude was significantly reduced in aged animals exposed to enriched conditions. The results indicate that the amplitude of the AHP in hippocampal pyramidal cells from aged animals is dependent on the history of experience and hippocampal activity.

Action Potentials↗

PubMed2005

Oral dosage form performance tests: new dissolution approaches.

The performance test is one of a series of tests that compose the specification in a United States Pharmacopeia (USP) dosage form monograph. For an orally administered, nonsolution dosage form, it is usually satisfied by either a dissolution or disintegration procedure. Dissolution acceptance criteria are usually set in private negotiations between an applicant and a regulatory agency. With information about this private agreement and other information provided in a sponsor's Request for Revision to USP, the USP's Council of Experts elaborates a public dosage form monograph. Based on the relationship between the regulatory decisions and the Request for Revision, the USP dissolution procedure links to a regulatory judgment about bioavailability and bioequivalence and, ultimately, to a judgment about safety and efficacy. The current dissolution procedure and acceptance criteria are perceived as having worked well over the years and are generally accepted. This article discusses new approaches that merit consideration. These approaches focus on a) explicit use of hypothesis testing, b) use of parametric tolerance intervals, c) improved ways to set dissolution acceptance criteria, and d) a more flexible protocol to assess conformity. Application of the proposed approaches may better assess, manage, and communicate both manufacturer and consumer risk for dissolution testing.

Administration, Oral↗