519: Small-molecule nitric oxide–releasing diazeniumdiolate for treating Pseudomonas aeruginosa infections

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.

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Doxycycline-Loaded Nitric Oxide-Releasing Nanomatrix Gel in Replanted Rat Molar on Pulp Regeneration

Applied Sciences ◽

10.3390/app11136041 ◽

2021 ◽

Vol 11 (13) ◽

pp. 6041

Author(s):

Kwan-Hee Yun ◽

Mi-Ja Ko ◽

Yong-Kown Chae ◽

Koeun Lee ◽

Ok-Hyung Nam ◽

...

Keyword(s):

Nitric Oxide ◽

Standard Deviation ◽

Treatment Group ◽

Root Surface ◽

Lower Grade ◽

Histomorphometric Analysis ◽

Pulp Regeneration ◽

Pulp Inflammation ◽

Nitric Oxide Releasing ◽

Rat Molar

The aim of the present study was to evaluate the effect of doxycycline-loaded NO-releasing nanomatrix gel on pulp regeneration in replantation of avulsed rat teeth. A total of 28 maxillary first molars extracted from rats were replanted. The rats were divided into two groups based on the use of root surface treatment: doxycycline-loaded NO-releasing nanomatrix group and no treatment. Eight weeks after replantation, the rats were sacrificed, and the teeth were evaluated using histomorphometric analysis. On histomorphometric analysis, the NO-releasing nanomatrix group demonstrated a significantly lower grade of pulp inflammation (1.00 ± 1.11, mean ± standard deviation) compared to the no treatment group (2.21 ± 1.25, p = 0.014). NO-releasing nanomatrix group showed a significantly higher grade of pulp regeneration (2.57 ± 0.85, p = 0.012) and significantly lower grade of pulp inflammation (1.00 ± 0.68, p = 0.025) compared to the no treatment group. In conclusion, NO-releasing nanomatrix gel improved pulp regeneration of replanted teeth, though the sample size of this study was rather small. Within the limits of this study, NO-releasing nanomatrix gel can provide more favorable pulpal regeneration despite replantation.

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