The role of copper/zinc-containing superoxide dismutase (cSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in metabolic defense against 02 toxicity in Drosophila is examined through the properties of a mutant strain carrying a cSOD-null mutation, cSOD1'08. Homozygotes are viable as larvae, which indicates that cSOD is not essential for cell viability per se. cSOD"'0 confers recessive sensitivity to the superoxide anion (O )-generator paraquat and to the transition metal compound CuS04, which indicates that the cSOD-nufl condition in fact leads to impaired°2 metabolism.The primary biological consequences of the reduced°2 dismutation capacity of cSOD"IY Drosophila are realized in the adult as infertility and reduction in life-span. We conclude that the infertility and reduced life-span of cSODR"'O adults arise as a consequence of the reduced capacity of embryos, larvae, and pupae to adequately protect developing preimaginal cells from 02-jnitiated cytotoxic damage.

This pilot randomized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide (inhNO) on lung function, morbidity, and mortality. Thirty patients with ARDS were randomly allocated to usual care or usual care plus inhNO. The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first 24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to 14.9% in the control group (p = 0.05). After the first day of therapy no further beneficial effect of inhNO was detected. Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after randomization compared with 33.3% in the control group (p = 0.83). The 30-d mortality rate was similar in the two groups; most deaths (11 of 17) were due to multiple organ dysfunction syndrome. This study shows that inhNO, in this population, may improve gas exchange but does not affect mortality.

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