Mitochondrial complexes I, II, and III were studied in isolated brain mitochondrial preparations with the goal of determining their relative abilities to reduce O2 to hydrogen peroxide (H2O2) or to reduce the alternative electron acceptors nitroblue tetrazolium (NBT) and diphenyliodonium (DPI). Complex I and II stimulation caused H2O2 formation and reduced NBT and DPI as indicated by dichlorodihydrofluorescein oxidation, nitroformazan precipitation, and DPI‐mediated enzyme inactivation. The O2 consumption rate was more rapid under complex II (succinate) stimulation than under complex I (NADH) stimulation. In contrast, H2O2 generation and NBT and DPI reduction kinetics were favored by NADH addition but were virtually unobservable during succinate‐linked respiration. NADH oxidation was strongly suppressed by rotenone, but NADH‐coupled H2O2 flux was accelerated by rotenone. α‐Phenyl‐N‐tert‐butyl nitrone (PBN), a compound documented to inhibit oxidative stress in models of stroke, sepsis, and parkinsonism, partially inhibited complex I‐stimulated H2O2 flux and NBT reduction and also protected complex I from DPI‐mediated inactivation while trapping the phenyl radical product of DPI reduction. The results suggest that complex I may be the principal source of brain mitochondrial H2O2 synthesis, possessing an “electron leak” site upstream from the rotenone binding site (i.e., on the NADH side of the enzyme). The inhibition of H2O2 production by PBN suggests a novel explanation for the broad‐spectrum antioxidant and antiinflammatory activity of this nitrone spin trap.

Preexisting physician attitudes, knowledge, and beliefs prevent emergency physicians from addressing PC needs for AD patients.

No abstract

Application of a microsystem-based strategy that engaged patients and families as well as caregivers brought about substantial changes in CF care delivery, increased satisfaction among staff and patients, and decreased hospital length of stay.

No abstract