Mechanical compression attenuates normal human bronchial epithelial wound healing

Background: Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods: Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH(2)O), and 4) 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results: We found that mechanical compression and scrape injury increase TGF-beta 2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE(2) media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE(2), but not EGF. Conclusion: Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE(2) and a compromised cytoskeleton

Home care in Europe: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Health and social services provided at home are becoming increasingly important. Hence, there is a need for information on home care in Europe. The objective of this literature review was to respond to this need by systematically describing what has been reported on home care in Europe in the scientific literature over the past decade.</p> <p>Methods</p> <p>A systematic literature search was performed for papers on home care published in English, using the following data bases: Cinahl, the Cochrane Library, Embase, Medline, PsycINFO, Sociological Abstracts, Social Services Abstracts, and Social Care Online. Studies were only included if they complied with the definition of home care, were published between January 1998 and October 2009, and dealt with at least one of the 31 specified countries. Clinical interventions, instrument developments, local projects and reviews were excluded. The data extracted included: the characteristics of the study and aspects of home care 'policy & regulation', 'financing', 'organisation & service delivery', and 'clients & informal carers'.</p> <p>Results</p> <p>Seventy-four out of 5,133 potentially relevant studies met the inclusion criteria, providing information on 18 countries. Many focused on the characteristics of home care recipients and on the organisation of home care. Geographical inequalities, market forces, quality and integration of services were also among the issues frequently discussed.</p> <p>Conclusions</p> <p>Home care systems appeared to differ both between and within countries. The papers included, however, provided only a limited picture of home care. Many studies only focused on one aspect of the home care system and international comparative studies were rare. Furthermore, little information emerged on home care financing and on home care in general in Eastern Europe. This review clearly shows the need for more scientific publications on home care, especially studies comparing countries. A comprehensive and more complete insight into the state of home care in Europe requires the gathering of information using a uniform framework and methodology.</p

Polycomb-Like 3 Promotes Polycomb Repressive Complex 2 Binding to CpG Islands and Embryonic Stem Cell Self-Renewal

Polycomb repressive complex 2 (PRC2) trimethylates lysine 27 of histone H3 (H3K27me3) to regulate gene expression during diverse biological transitions in development, embryonic stem cell (ESC) differentiation, and cancer. Here, we show that Polycomb-like 3 (Pcl3) is a component of PRC2 that promotes ESC self-renewal. Using mass spectrometry, we identified Pcl3 as a Suz12 binding partner and confirmed Pcl3 interactions with core PRC2 components by co-immunoprecipitation. Knockdown of Pcl3 in ESCs increases spontaneous differentiation, yet does not affect early differentiation decisions as assessed in teratomas and embryoid bodies, indicating that Pcl3 has a specific role in regulating ESC self-renewal. Consistent with Pcl3 promoting PRC2 function, decreasing Pcl3 levels reduces H3K27me3 levels while overexpressing Pcl3 increases H3K27me3 levels. Furthermore, chromatin immunoprecipitation and sequencing (ChIP-seq) reveal that Pcl3 co-localizes with PRC2 core component, Suz12, and depletion of Pcl3 decreases Suz12 binding at over 60% of PRC2 targets. Mutation of conserved residues within the Pcl3 Tudor domain, a domain implicated in recognizing methylated histones, compromises H3K27me3 formation, suggesting that the Tudor domain of Pcl3 is essential for function. We also show that Pcl3 and its paralog, Pcl2, exist in different PRC2 complexes but bind many of the same PRC2 targets, particularly CpG islands regulated by Pcl3. Thus, Pcl3 is a component of PRC2 critical for ESC self-renewal, histone methylation, and recruitment of PRC2 to a subset of its genomic sites

Openings in frog microvascular endothelium at different rates of increase in pressure and at different temperatures

Experiments were carried out on single mesenteric capillaries and venules of pithed frogs to determine whether the rate of increase in intravascular pressure (dP/dt) influenced the critical pressure (PB) which increases wall permeability. Vessels, microperfused with frog Ringer solutions containing 0.1 % bovine serum albumin and red cells, were occluded downstream before pressure was raised either as a ramp or in a series of 13.6 cmH2O steps. By varying step duration, the mean dP/dt could be matched to dP/dt applied as a steady ramp. PB was recorded as the pressure at which there was an abrupt increase in filtration with red cells passing to and through one or more sites in the vessel wall. In all vessels, increasing dP/dt raised PB, with no differences between steps and ramps. The relation between PB and dP/dt was linear, consistent with a latent period, T (the slope), between a critical pressure being reached and the abrupt increase in permeability being observed. Direct observation confirmed this latent period. Between 12 and 20 oC, T was 8.5 ± 0.47 s; between 0 and 5 °C, T was 11.5 ± 0.97 s. Tissue cooling did not influence the time constant, τ, describing the rate of stretch of wall following a step increase in pressure and used to measure wall visco-elastic properties. Nor was the value of τ (1.15 ± 0.06 s, n = 42) consistent with T being accounted for by visco-elasticity. It is suggested that the latent period may indicate an active response of the endothelium