Should I stay or should I go? Pulmonary embolism and air travel

Many respiratory conditions can affect a passenger’s fitness to fly with pulmonary embolism being the most debatable. A major question that respiratory physicians frequently have to answer, mostly with visitors from overseas who need to be repatriated following diagnosis of pulmonary embolism, is about the right time to “fly with a clot”. Risk of flying after being diagnosed with pulmonary embolism is not the same for all patients and in every case we should take into consideration the risk stratification on presentation and the PaO2 level

Epithelium-dependent regulation of airways smooth muscle function. A histamine-nitric oxide pathway

The airway epithelium is responsible for the production of a number of arachidonic acid and nonprostanoid inhibitory factors. Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM100 μ M) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KCl in the presence or not of 10-5 Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 μ M) on KCl contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p<0.01). Epithelium removal increased the contraction induced by KCl (80 mM) and histamine (1 μ M) by about 30% (p<0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma

Airway responsiveness: role of inflammation, epithelium damage and smooth muscle tension.

The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh) (10(-5) M)-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g) before and after epithelium removal. At low resting tension (0.5-1.5 g), the epithelium removal decreased the ACh-induced contractions. At 2 g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (P<0.01). Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged

Epithelium-dependent effect of L-glutamate on airways: involvement of prostaglandins.

We investigated the effect of the excitatory amino acid (EAA) receptor agonists L-glutamate, N-methyl-D-aspartate (NMDA), (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on KCl-induced contractions of rabbit tracheal smooth muscle, as well as the role of epithelium and endogenously produced nitric oxide and prostaglandins on these responses. L-Glutamate decreased KCI-induced contractions up to 30%. This effect was attenuated by epithelium removal, tetrodotoxin, methylene blue and indomethacin but not by NG-nitro-L-arginine methyl ester. While NMDA, AMPA and kainic acid had no effect, the combination of NMDA + kainic acid decreased KCI-induced contractions. These results suggest that, in rabbit trachea, L-glutamate has, at least in part, an epithelium-dependent effect mediated via prostaglandin formation and that the EAA receptors involved are non-classical

Epithelium-dependent regulation of airways smooth muscle function. A histamine-nitric oxide pathway.

The airway epithelium is responsible for the production of a number of arachidonic acid and non-prostanoid inhibitory factors. Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM-100 microM) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KC1 in the presence or not of 10(-5) Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 microM) on KC1 contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p<0.01). Epithelium removal increased the contraction induced by KC1 (80 mM) and histamine (1 microM) by about 30% (p<0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma

Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro

Background: Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs increase paracellular permeability via the disruption of tight junction (TJ) proteins occludin and claudin. In the present study it was investigated if MMP2 and MMP9 alter permeability properties of the pleura tissue by degradation of TJ proteins in pleural mesothelium. Results: In the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression. Conclusions: MMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms. Backgroun

Resting Tension Affects eNOS Activity in a Calcium-Dependent Way in Airways

The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), NG-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way

Pleural Transport Physiology: Insights from Biological Marker Measurements in Transudates

Aims: The aim of this study was to evaluate the physicochemical properties of the pleural mesothelial barrier and of the biological markers that facilitate or eliminate the passage of molecules through the pleura. Methods and Material: Pleural fluid samples from sixty-five patients with heart failure were analyzed. The biological markers studied were lactate dehydrogenase (LDH), adenosine deaminase (ADA), interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), carcinoembryonic antigen (CEA), copper/zinc superoxide dismutase (CuZnSOD), matrix metalloproteinase-2 (MMP-2), -3 (MMP-3), -7(MMP-7), -8 (MMP-8) and -9 (MMP-9). Based on the pleural fluid/serum ratio, these molecules were divided into three groups: a) the LDH-like group with a pleural fluid/serum ratio between 0,4 and 0,8 (LDH, CEA, CuZnSOD, ADA, CRP, MMP-8), b) molecules with a pleural fluid/serum ratio less than 0,4 (MMP-7 and MMP-9) and c) molecules with a pleural fluid/serum ratio equal or above 1 (TNF-α, IL-6, MMP-2 and MMP-3). Results: No correlation between the molecular radius and the pleural fluid to serum ratio of the above biological markers was found. Conclusions: The molecular size is not a major determinant for the passage of molecules through the mesothelial barrier. Several other factors may influence the transport of the above molecules to pleural cavity, such as their charge and shape. © Eleni et al

Factors associated with adolescent cigarette smoking in Greece: Results from a cross sectional study (GYTS Study)

<p>Abstract</p> <p>Background</p> <p>Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study.</p> <p>Methods</p> <p>A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004–2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal.</p> <p>Results</p> <p>6141 adolescents (51.5% males and 48.5% females) participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08–3.08), parental smoking (OR: 2.59; 95% CI: 1.45–5.89), and having pocket money ≥ 16 Euros (OR: 2.64; 95% CI: 1.19–5.98).</p> <p>Conclusion</p> <p>Male gender, parental smoking, and having pocket-money ≥ 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.</p

In Silico Transcriptomic Analysis of Wound-Healing-Associated Genes in Malignant Pleural Mesothelioma.

Background and objectives: Malignant pleural mesothelioma (MPM) is a devastating malignancy with poor prognosis. Reliable biomarkers for MPM diagnosis, monitoring, and prognosis are needed. The aim of this study was to identify genes associated with wound healing processes whose expression could serve as a prognostic factor in MPM patients. Materials and Methods: We used data mining techniques and transcriptomic analysis so as to assess the differential transcriptional expression of wound-healing-associated genes in MPM. Moreover, we investigated the potential prognostic value as well as the functional enrichments of gene ontologies relative to microRNAs (miRNAs) of the significantly differentially expressed wound-healing-related genes in MPM. Results: Out of the 82 wound-healing-associated genes analyzed, 30 were found significantly deregulated in MPM. Kaplan-Meier analysis revealed that low ITGAV gene expression could serve as a prognostic factor favoring survival of MPM patients. Finally, gene ontology annotation enrichment analysis pointed to the members of the hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members as important regulators of the deregulated wound healing genes. Conclusions: 30 wound-healing-related genes were significantly deregulated in MPM, which are potential targets of hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members. Out of those genes, ITGAV gene expression was a prognostic factor of overall survival in MPM. Our results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally