In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres

Clinical and manometric characteristics of allgrove syndrome

OBJECTIVE: The association of adrenocorticotropic hormone (ACTH) insensitivity with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare multisystem disorder. Its evolution is not well known. The aim of this study was to describe clinical and esophageal manometric characteristics and outcomes in Allgrove syndrome. PATIENTS AND METHODS: This multicenter retrospective study compared clinical and manometric characteristics at diagnosis and on follow-up of 9 children presenting with 3A (mean age at diagnosis 7.1 years) with those of 9 children with idiopathic achalasia (IA) (mean age at diagnosis 8.3 years). RESULTS: At the time of diagnosis, 3 children with 3A presented with no digestive or respiratory signs because they were identified during a family screening; 1 remained asymptomatic 8 years later. ACTH levels were high in patients with 3A. All of the patients with IA were symptomatic at diagnosis. No significant difference was observed when comparing any of the manometric parameters of the first esophageal manometry of 3A with those of IA. Seven children with 3A were operated on using the Heller procedure, completed by pneumatic esophageal dilation in 2 of these 7. One patient with 3A was treated only by nifedipine. Failure of treatment was observed in 3 children with 3A and 1 child with IA, partial success in 4 with 3A and 1 with IA, and total success in 2 with 3A and 7 with IA (P<0.03). Control manometry showed that in the 3A group, partial success after surgery was always associated with abnormally low or normal lower esophageal sphincter (LES) pressure, whereas failure after surgery was associated with high LES pressure. CONCLUSIONS: Our data showed that 3A presented a more severe course than IA despite presymptomatic diagnosis in cases of family screening. The high LES pressure noted in some patients with 3A is suggestive of a peculiar pattern in 3A affecting the LES and the lower part of the esophagus. Copyright © 2011 by European Society for Pediatric Gastroenterology.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres