Developmental changes in nitric oxide synthase isoform expression and nitric oxide production in fetal baboon lung

. Developmental changes in nitric oxide synthase isoform expression and nitric oxide production in fetal baboon lung. Am J Physiol Lung Cell Mol Physiol 283: L1192-L1199, 2002. First published July 3, 2002 10.1152/ajplung.00112.2002, produced by NO synthase (NOS), plays a critical role in multiple processes in the lung during the perinatal period. To better understand the regulation of pulmonary NO production in the developing primate, we determined the cell specificity and developmental changes in NOS isoform expression and action in the lungs of third-trimester fetal baboons. Immunohistochemistry in lungs obtained at 175 days (d) of gestation (term ϭ 185 d) revealed that all three NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), are primarily expressed in proximal airway epithelium. In proximal lung, there was a marked increase in total NOS enzymatic activity from 125 to 140 d gestation due to elevations in nNOS and eNOS, whereas iNOS expression and activity were minimal. Total NOS activity was constant from 140 to 175 d gestation, and during the latter stage (160-175 d gestation), a dramatic fall in nNOS and eNOS was replaced by a rise in iNOS. Studies done within 1 h of delivery at 125 or 140 d gestation revealed that the principal increase in NOS during the third trimester is associated with an elevation in exhaled NO levels, a decline in expiratory resistance, and greater pulmonary compliance. Thus, there are developmental increases in pulmonary NOS expression and NO production during the early third trimester in the primate that may enhance airway and parenchymal function in the immediate postnatal period. airway epithelium; compliance; expiratory resistance; primate THE SIGNALING MOLECULE nitric oxide (NO), produced by nitric oxide synthase (NOS), plays a critical role in physiological processes in the pulmonary epithelium There is mounting evidence that NO is of great importance to lung epithelial function in the perinatal period. The stimulation of NO synthesis by acetylcholine or bradykinin causes marked decreases in lung liquid production in late-gestation fetal lambs We and others have shown that the pulmonary expression of the neuronal and endothelial isoforms of NOS (nNOS and eNOS) in nonprimate mammalian species increases during fetal lif

From in vivo to in vitro : The medical device testing paradigm shift

Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them. Bringing about change will require a paradigm shift in current approaches to testing - and a concerted effort to generate better data on risks to human health from exposure to leachable chemicals from medical devices, and to boost confidence in the use of alternative methods to test devices. To help advance these ideas, stir debate about best practices, and coalesce around a roadmap forward, the JHU-Center for Alternatives to Animal Testing (CAAT) hosted a symposium believed to be the first gathering dedicated to the topic of in vitro testing of medical devices. Industry representatives, academics, and regulators in attendance presented evidence to support the unique strengths and challenges associated with the approaches currently in use as well as new methods under development, and drew next steps to push the field forward from their presentations and discussion.publishe

Analysing how law shapes journalism in Central and Eastern Europe: the case of the 2008 Slovak Press Act

This article investigates the operation of the contested reply and correction provisions of the 2008 Slovak Press Act and their influence on journalism. I argue that apart from the 'law-on-the-books', we need to examine the interactions between the media, policymakers and judges in order to explain how law shapes journalism in the public spheres of Central and Eastern European democracies. Such interactions are based on the interests and experiences of the actors and conditioned by their particular historical, structural, cultural and international contexts. Our analysis thus needs to take them all into account when assessing the role of legislation