Inhibition of co-colonizing cystic fibrosis-associated pathogens by Pseudomonas aeruginosa and Burkholderia multivorans.

Cystic fibrosis (CF) is a recessive genetic disease characterized by chronic respiratory infections and inflammation causing permanent lung damage. Recurrent infections are caused by Gram-negative antibiotic-resistant bacterial pathogens such as Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and the emerging pathogen genus Pandoraea. In this study, the interactions between co-colonizing CF pathogens were investigated. Both Pandoraea and Bcc elicited potent pro-inflammatory responses that were significantly greater than Ps. aeruginosa. The original aim was to examine whether combinations of pro-inflammatory pathogens would further exacerbate inflammation. In contrast, when these pathogens were colonized in the presence of Ps. aeruginosa the pro-inflammatory response was significantly decreased. Real-time PCR quantification of bacterial DNA from mixed cultures indicated that Ps. aeruginosa significantly inhibited the growth of Burkholderia multivorans, Burkholderia cenocepacia, Pandoraea pulmonicola and Pandoraea apista, which may be a factor in its dominance as a colonizer of CF patients. Ps. aeruginosa cell-free supernatant also suppressed growth of these pathogens, indicating that inhibition was innate rather than a response to the presence of a competitor. Screening of a Ps. aeruginosa mutant library highlighted a role for quorum sensing and pyoverdine biosynthesis genes in the inhibition of B. cenocepacia. Pyoverdine was confirmed to contribute to the inhibition of B. cenocepacia strain J2315. B. multivorans was the only species that could significantly inhibit Ps. aeruginosa growth. B. multivorans also inhibited B. cenocepacia and Pa. apista. In conclusion, both Ps. aeruginosa and B. multivorans are capable of suppressing growth and virulence of co-colonizing CF pathogens.

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. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three showing a comparable or greater level of virulence in vivo relative to another CF pathogen, Burkholderia cenocepacia, whilst strains from two other species, Pandoraea apista and Pandoraea pnomenusa, were considerably less virulent. For all Pandoraea species, whole cells were required for larval killing, as cell-free supernatants had little effect on larval survival. Overall, invasive Pandoraea strains showed comparable invasion of two independent lung epithelial cell lines, irrespective of whether they had a CF phenotype. Pandoraea strains were also capable of translocation across polarized lung epithelial cell monolayers. Although protease secretion was a common characteristic across the genus, it is unlikely to be involved in pathogenesis. In conclusion, whilst multiple mechanisms of pathogenicity may exist across the genus Pandoraea, it appears that lung cell invasion and translocation contribute to the virulence of P. pulmonicola strains.

Acamprosate calcium as augmentation therapy for anxiety disorders.

BACKGROUND: Glutamate is a major excitatory neurotransmitter, while γ-aminobutyric acid (GABA) is a predominant inhibitory neurotransmitter in the central nervous system. This GABA-glutamate imbalance is thought to play a role in the development of anxiety. Acamprosate calcium is thought to restore this chemical imbalance in alcohol withdrawal. OBJECTIVE: To examine acamprosate calcium as augmentation therapy for treatment of anxiety. METHODS: This 8-week, open-label study was designed to evaluate patients with anxiety who were stable on current medications (selective serotonin-reuptake inhibitors and serotonin-norepinephrine-reuptake inhibitors) but still symptomatic. Acamprosate was dosed at 1998 mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and the Hospital Anxiety and Depression Scale. RESULTS: Thirteen patients enrolled in the study and received study medication. Acamprosate reduced anxiety symptoms (mean HAM-A score reduction to 8.87 from a baseline of 20). Sixty-two percent of patients receiving acamprosate achieved remission (HAM-A score ≤ 7). Modal dose was 1998 mg/day (range 999-1998). The most commonly reported adverse events were nausea (n = 1), gastrointestinal upset (n = 1), and increased dream activity (n = 1). CONCLUSIONS: Acamprosate calcium may be effective augmentation therapy in patients with treatment-resistant anxiety.

"A comparison of the effectiveness of two hypnotic agents for the treatment of insomnia".

OBJECTIVE: To compare the effectiveness and tolerability of two hypnotic agents, trazadone (Desyrel) and zaleplon (Sonata) on psychiatric inpatients with insomnia. METHODS: Fifteen patients who were psychiatric inpatients were assigned openly and randomly to receive either trazodone (50-100 mg) or zaleplon (10-20 mg) doses on an "as-needed basis" and followed throughout their hospital stay. Efficacy and side effect profile were subsequently assessed. CONCLUSION: This pilot study suggests that trazodone may be a better agent to promote longer, deeper subjective quality sleep for psychiatric inpatients with insomnia in terms of effectiveness. However, tolerability was much better with zaleplon as daytime residual side effects were less.