Archive for the ‘Pneumonia’ Category

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Conclusion

This suggests that nebulized nitrite exposure in mice with pneumonia-induced pulmonary inflammation could result in intrapulmonary NO-dependent oxidative (nitrosative) effects. However, as DETA-NO and exhausted DETA were equally antibacterial in vitro, and as NaNO2 had a minimal effect, it is likely that NO and nitrite derived from DETA-NO did not play an important role in […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: NONOates

When NONOates are administered IV, they have been shown to cause both systemic and pulmonary vasodilation in animals. The rate of NO release and the resulting degree of vasodilation are related to the chemistry of the nucleophile moiety of the individual NONOate compounds. The intratracheal instillation of NONOate has been shown to selectively dilate the […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: iNO

NONOates, adducts of NO and various nucleophile moieties, are distinct NO donors that spontaneously and nonenzymatically release NO at predictable rates. The in vivo decomposition studies described in the present report confirm continuous intrapulmonary NO release for at least 12 to 24 h following the exposure of mice to nebulized DETA-NO. Although the mice clearly […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Mice with pneumonia

Discussionxposure to nebulized DETA-NO, a NO donor, is associated with significant, prolonged intrapulmo-nary NO release in mice. In a mouse model of P aeruginosa pneumonia, the intermittent nebuliza-tion of DETA-NO significantly attenuated intrapul-monary bacterial growth. However, a possible in vivo antibacterial effect of exogenous NO was not confirmed during the administration of iNO, which at […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Effects Of DETA-NO and iNO

Effects Of DETA-NO and iNO on Endogenous NO Levels In pilot studies, exposure to a single dose of 125 ^mol nebulized DETA-NO was associated with increased eNO and plasma NOx~ levels but no change in NOx~ levels in BAL fluid (Fig 4). eNO levels increased markedly within 30 min, which is consistent with intrapulmonary NO […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Pulmonary Neutrophil Infiltration

However, the nebulization of 2.5 ^mol DETA-NO had no significant effect on pulmonary bacterial load (data not shown). In contrast to DETA-NO exposure, iNO exposure was associated with an increased pulmonary bacterial load at 40 ppm (241 ± 55% of the bacterial load in mice in the untreated pneumonia group; p < 0.05) but not […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Statistical Analysis

Thus, P aeruginosa cultures also were incubated under the following control conditions: (1) in the presence of exhausted DETA-NO (0.5, 5, and 50 mM; generated by previously incubating DETA-NO in open polystyrene test tubes at 60°C for 24 h); and (2) NaNO2 (0.5, 5, and 50 mM). Following exposure to DETA-NO, exhausted DETA-NO, or NaNO2, […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Plasma NO Metabolites

Analysis of Plasma NO Metabolites (Nitrites and Nitrates) Plasma levels of nitrites and nitrates were collectively measured as NOx— by chemiluminescence, as previously described. Briefly, plasma was refluxed in saturated vanadium chloride in hydrochloric acid, resulting in the reduction of NOx— to NO, which is detected by chemiluminescence (model 270B NO analyzer; Sievers Instruments; Boulder, […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: MPO

The heart and lungs were removed en bloc, and the pulmonary vasculature was perfused with 10 mL saline solution through a right ventriculotomy. Lung tissue was homogenized in 1 mL 10 mM bicarbonate-free N-2-hydroxyeth-ylpiperazine-N’-2-ethanesulfonic acid buffer (containing 0.1 mM ethylenediaminetetraacetic acid, 1 mg/mL phenylmethylsulfonyl fluoride, 1 mM dithiothreitol, and 0.32 M sucrose [pH 7.4]) at […]

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Exposure to INO

In a subset of animals, exhaled NO (eNO) levels were serially measured noninvasively before and 0.5, 2, 6, 12, and 24 h after the single DETA-NO nebulization, as previously described. In brief, spontaneously breathing mice were individually placed in a small plastic chamber that was flushed with NO-free medical-grade air at 60 mL/min. The chamber […]

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