Heteroleptic Coumarin-Based Silver(I) Complexes: Possible New Antimicrobial Agents.

Heteroleptic coumarin-based silver(I) complexes with improved solubility profiles were synthesised using either triphenylphosphine or an -heterocyclic carbene as adduct ligands, and were fully characterised using IR and NMR spectroscopy, elemental analysis, and, where possible, X-ray crystallography. The triphenylphosphine adducts formed well-resolved structures, where the oxyacetate ligands asymmetrically chelated the silver(I) ion in a bidentate chelating mode, and the silver(I) ion was also bound to two triphenylphosphine ligands. The solubility profile and photostability of the adducts were considerably improved compared to those of previously isolated simple coumarin silver(I) complexes.

Macrophage migration inhibitory factor enhances biofilm formation, potentially contributing to cystic fibrosis pathogenesis.

Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator that we have previously shown to be associated with an aggressive clinical phenotype in cystic fibrosis. It possesses unique tautomerase enzymatic activity. However, to date, no human-derived substrate has been identified that has the capacity to interact with this cytokine's unique tautomerase activity.

Current and Emerging Therapies for the Treatment of Cystic Fibrosis or Mitigation of Its Symptoms.

Clinical presentation of the chronic, heritable condition cystic fibrosis (CF) is complex, with a diverse range of symptoms often affecting multiple organs with varying severity. The primary source of morbidity and mortality is due to progressive destruction of the airways attributable to chronic inflammation arising from microbial colonisation. Antimicrobial therapy combined with practises to remove obstructive mucopurulent deposits form the cornerstone of current therapy.

Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms.

Pulmonary infection with Burkholderia cepacia complex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on mature B. cepacia complex biofilms, both in the presence and absence of CF sputum.

Residence in biofilms allows Burkholderia cepacia complex (Bcc) bacteria to evade the antimicrobial activities of neutrophil-like dHL60 cells.

Bacteria of the Burkholderia cepacia complex (Bcc) persist in the airways of people with cystic fibrosis (CF) despite the continuous recruitment of neutrophils. Most members of Bcc are multidrug resistant and can form biofilms. As such, we sought to investigate whether biofilm formation plays a role in protecting Bcc bacteria from neutrophils.

Mcl-1 is vital for neutrophil survival.

Upon entry to the systemic circulation, neutrophils exhibit a short mean time to cell death. The viability of most cell types in a steady state is preserved by the interplay of the Bcl-2 family of proteins, wherein the anti-apoptotic members inhibit the action of their pro-apoptotic counterparts. Neutrophils, however, display absent or severely reduced expression of several anti-apoptotic Bcl-2 family proteins.

Virulence of an emerging respiratory pathogen, genus Pandoraea, in vivo and its interactions with lung epithelial cells.

Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P.

Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung epithelial cells.

Pandoraea species are emerging opportunistic pathogens capable of causing chronic lung infections in cystic fibrosis patients. This study examined the interactions of 17 Pandoraea isolates from the five identified species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells and their ability to form biofilms in vitro. Only three isolates showed an ability to invade A549 lung epithelial cells, and only one isolate was able to form biofilms.

The effect of recombinant human lactoferrin on growth and the antibiotic susceptibility of the cystic fibrosis pathogen Burkholderia cepacia complex when cultured planktonically or as biofilms.

Objectives: The cystic fibrosis (CF) pathogen Burkholderia cepacia complex (Bcc) is innately resistant to antibiotics and the development of effective therapeutic strategies to treat these infections is a major challenge. The objectives of this study were to investigate the effects of recombinant human lactoferrin (rHL) on planktonic and biofilm cultures of Bcc organisms and to establish whether lactoferrin alters the susceptibility of these cultures to a range of antibiotic therapies.

Methods: Planktonic and biofilm cultures of strains representative of three species of Bcc, Burkholderia multivorans, Burkholderia cenocepacia and Burkholderia dolosa, were exposed to 0-900 mg/L lactoferrin over 0-48 h.

Coagulopathy after cardiac surgery may be influenced by a functional plasminogen activator inhibitor polymorphism.

Background: Cytokine-mediated inflammation and coagulopathy may occur after cardiac surgery. In this study we investigated the temporal pattern of plasminogen activator inhibitor-1 (PAI-1) gene expression after cardiac surgery and its relation with PAI genotype, and obtained preliminary data regarding its relation to perioperative morbidity.

Methods: The relative change in PAI-1 mRNA 1, 6, and 24 h after cardiopulmonary bypass (CPB) was measured from mononuclear cells in 82 patients undergoing elective cardiac surgery.

Invasion and biofilm formation of Burkholderia dolosa is comparable with Burkholderia cenocepacia and Burkholderia multivorans.

Background: Colonisation with Burkholderia cepacia complex pathogens has been associated with accelerated decline in cystic fibrosis (CF) patients. The two most common species among the CF community are Burkholderia cenocepacia and Burkholderia multivorans. However, Burkholderia dolosa has recently been causing concern due to its transmissibility and virulence in CF patients.

Tumor necrosis factor-alpha and interleukin-10 gene expression in peripheral blood mononuclear cells after cardiac surgery.

Objective: Cytokine response after cardiac surgery may be genetically influenced. A study was carried out to investigate the relation between cytokine gene expression in peripheral blood mononuclear cells, genotype, and clinical events after cardiac surgery.

Design: A case-control study was performed.