Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury

Quantitative trait analysis of the development of pulmonary tolerance to inhaled zinc oxide in mice

BACKGROUND: Individuals may develop tolerance to the induction of adverse pulmonary effects following repeated exposures to inhaled toxicants. Previously, we demonstrated that genetic background plays an important role in the development of pulmonary tolerance to inhaled zinc oxide (ZnO) in inbred mouse strains, as assessed by polymorphonuclear leukocytes (PMNs), macrophages, and total protein in bronchoalveolar lavage (BAL) phenotypes. The BALB/cByJ (CBy) and DBA/2J (D2) strains were identified as tolerant and non-tolerant, respectively. The present study was designed to identify candidate genes that control the development of pulmonary tolerance to inhaled ZnO. METHODS: Genome-wide linkage analyses were performed on a CByD2F2 mouse cohort phenotyped for BAL protein, PMNs, and macrophages following 5 consecutive days of exposure to 1.0 mg/m(3 )inhaled ZnO for 3 hours/day. A haplotype analysis was carried out to determine the contribution of each quantitative trait locus (QTL) and QTL combination to the overall BAL protein phenotype. Candidate genes were identified within each QTL interval using the positional candidate gene approach. RESULTS: A significant quantitative trait locus (QTL) on chromosome 1, as well as suggestive QTLs on chromosomes 4 and 5, for the BAL protein phenotype, was established. Suggestive QTLs for the BAL PMN and macrophage phenotypes were also identified on chromosomes 1 and 5, respectively. Analysis of specific haplotypes supports the combined effect of three QTLs in the overall protein phenotype. Toll-like receptor 5 (Tlr5) was identified as an interesting candidate gene within the significant QTL for BAL protein on chromosome 1. Wild-derived Tlr5-mutant MOLF/Ei mice were tolerant to BAL protein following repeated ZnO exposure. CONCLUSION: Genetic background is an important influence in the acquisition of pulmonary tolerance to BAL protein, PMNs, and macrophages following ZnO exposure. Promising candidate genes exist within the identified QTL intervals that would be good targets for additional studies, including Tlr5. The implications of tolerance to health risks in humans are numerous, and this study furthers the understanding of gene-environment interactions that are likely to be important factors from person-to-person in regulating the development of pulmonary tolerance to inhaled toxicants

Shell occupation by the hermit crab Dardanus insignis (Decapoda, Diogenidae) from the north Coast of São Paulo state, Brazil

Abstract The pattern of shell occupation by the hermit crab Dardanus insignis (Saussure, 1858) from the subtropical region of southeastern coast of Brazil was investigated in the present study. The percentage of shell types that were occupied and the morphometric relationships between hermit crabs and occupied shells were analyzed from monthly collections conducted during two years (from January 1998 to December 1999). Individuals were categorized according to sex and gonadal maturation, weighed and measured with respect to their cephalothoracic shield length (CSL) and wet weight (CWW). Shells were measured regarding their aperture width (SAW), dry weight (SDW) and internal volume (SIV). A total of 1086 hermit crabs was collected, occupying shells of 11 gastropod species. Olivancillaria urceus (Roding, 1798) was most commonly used by the hermit crab D. insignis, followed by Buccinanops cochlidium (Dillwyn, 1817), and Stramonita haemastoma (Linnaeus, 1767). The highest determination coefficients (r2 > 0.50, p < 0.01) were recorded particularly in the morphometric relationships between CSL vs. CWW and SAW vs. SIV, which are important indication that in this D. insignis population the great majority the animals occupied adequate shells during the two years analysed. The high number of used shell species and relative plasticity in pattern of shell utilization by smaller individuals of D. insignis indicated that occupation is influenced by the shell availability, while larger individuals demonstrated more specialized occupation in Tonna galea (Linnaeus, 1758) shell

Revisional bariatric surgery for failed restrictive procedures

Copyright © 2008 American Society for Metabolic and Bariatric Surgery Published by Elsevier Inc.Background Revisional bariatric surgery is increasing in frequency, but the morbidity and efficacy have not been well defined. The primary aim of this study was to determine the clinical efficacy with respect to weight loss, and associated morbidity, of revisional bariatric surgery in an academic university hospital bariatric surgery program. Methods A retrospective review of all patients who underwent revisional bariatric surgery for failed primary restrictive procedures, including gastroplasty and gastric bypass, but not including gastric banding or malabsorptive procedures, during a 10-year period at a single university hospital was performed. The perioperative morbidity and long-term weight loss and clinical results were determined from the medical charts. Results A total of 41 patients met the inclusion criteria. The primary bariatric procedures included vertical banded gastroplasty in 20 and Roux-en-Y gastric bypass in 21. The indications for revisional surgery included poor weight loss, weight regain, and various technical problems, including anastomotic stenosis and ulcer. The major morbidity rate was 17%. No patients died. The weight loss results varied depending on the indication for the revisional surgery and reoperative solution applied. The resolution of technical problems was achieved in all patients. Conclusion Revisional bariatric surgery can be performed with minimal mortality, albeit significant morbidity. The efficacy with respect to weight loss appeared acceptable, although the results were not as good as those after primary bariatric surgery. The analysis of patient subsets stratified by surgical history and revisional strategy provided important insights into the mechanisms of failure and efficacy of different revisional strategies.Brian A., Coakley B.A., Clifford W. Deveney, Donn H. Spight, Sarah K. Thompson, David Le, Blair A. Jobe, Bruce M. Wolfe, Donald B. McConnell and Robert W. O'Rourk