Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial

RATIONALE: COPD exacerbations are prone to non-recovery but there are no data about the effectiveness of retreatment on these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. METHODS: This multi-centre randomised double-blind placebo-controlled trial studied retreatment with oral ciprofloxacin 500mg or matched placebo twice daily for 7 days in patients with GOLD stage II - IV COPD with persistent symptoms and/or serum C-reactive protein (CRP) ≥8mg/L initiated 14 (+/- 3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period. RESULTS: Of 826 patients screened at 4 centres, 144 eligible participants with incomplete recovery were randomised to receive ciprofloxacin (n=72) or placebo (n=72). 57% of patients in the ciprofloxacin group had experienced 1 or more exacerbations, compared to 53% in the placebo group. The median time to the next exacerbation was 32.5 days (IQR 13-50) in the placebo arm and 34 days (IQR 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio = 1.07, 95% CI 0.68-1.68; p=0.76). No significant differences were seen in quality of life scores or lung function between treatment groups. CONCLUSION: In patients with persistent symptoms and/or raised CRP 14 days following a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared to placebo. This suggests that non-recovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with anti-inflammatory therapy

Searching for antigen B genes and their adaptive sites in distinct strains and species of the helminth Echinococcus.

Twenty-seven PCR-derived antigen B (AgB) nucleotide sequences from four Echinococcus species (Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthrus and Echinococcus vogeli) were aligned with 78 already published sequences, to generate a maximum likelihood phylogeny of the AgB multigene family. The phylogenetic analysis confirms that the family is constituted by four groups of genes present in each one of the four species (AgB1, AgB2, AgB3 and AgB4), and suggests that it originated by ancient duplication events preceding speciation within the genus. AgB5 sequences, which had been formerly suggested to correspond to a putatively new AgB subunit, cluster with AgB3. Likelihood tests suggest that AgB gene evolution may have been driven by heterogeneous selection pressures acting on particular AgB1, AgB3 and AgB4 codons. No selection is detected in AgB2. We discuss implications of our findings in terms of AgB biology and its use as a diagnostic tool

Searching for antigen B genes and their adaptive sites in distinct strains and species of the helminth Echinococcus.

Twenty-seven PCR-derived antigen B (AgB) nucleotide sequences from four Echinococcus species (Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthrus and Echinococcus vogeli) were aligned with 78 already published sequences, to generate a maximum likelihood phylogeny of the AgB multigene family. The phylogenetic analysis confirms that the family is constituted by four groups of genes present in each one of the four species (AgB1, AgB2, AgB3 and AgB4), and suggests that it originated by ancient duplication events preceding speciation within the genus. AgB5 sequences, which had been formerly suggested to correspond to a putatively new AgB subunit, cluster with AgB3. Likelihood tests suggest that AgB gene evolution may have been driven by heterogeneous selection pressures acting on particular AgB1, AgB3 and AgB4 codons. No selection is detected in AgB2. We discuss implications of our findings in terms of AgB biology and its use as a diagnostic tool

Bioartificial Sponges for Auricular Cartilage Engineering

Auricle reconstruction due to congenital, post-infective or post-traumatic defects represents a challenging procedure in the field of aesthetic and reconstructive surgery due to the highly complex three-dimensional anatomy of the outer ear. Tissue engineering aims to provide alternatives to overcome the shortcomings of standard surgical reconstructive procedure. In the present study, poly(vinyl alcohol)/gelatin (PVA/G) sponges at different weight ratios were produced via emulsion and freeze-drying, and crosslinked by exposure to glutaraldehyde vapors. PVA/G sponges gave rise to highly porous, water stable and hydrophilic scaffolds. Characterization of PVA/G sponges showed round-shaped interconnected pores, high swelling capacity (>200%) and viscoelastic mechanical behavior. The PVA/G 70/30 (w/w) scaffold was selected for in vitro biological studies. Bone marrow derived human mesenchymal stromal cells (hMSCs) were used and differentiated towards chondrogenic lineage under different culture conditions: 1) commercial versus handmade differentiation medium; 2) undifferentiated versus pre-differentiated hMSC seeding; and 3) static versus dynamic culture [i.e. ultrasound (US) or bioreactor stimulation]. Histological results highlighted intense glycosaminoglycan, glycoprotein and collagen syntheses after three weeks, mostly using the commercial medium, whereas round morphology was observed in pre-differentiated cells. In static culture, immunohistochemistry for chondrogenic markers revealed an early differentiation stage, characterized by the expression of Sox-9 and collagen type I fibers. The application of US on cell/scaffold constructs increased extracellular matrix deposition and resulted in 30% higher collagen type II expression at the gene level. Bioreactor culture induced collagen type II, aggrecan and elastin formation. This study demonstrated that 70/30 PVA/G sponge is a suitable candidate for auricle reconstruction