The increased susceptibility to hydrogen peroxide of the (post)-ischemic rat heart is associated with the magnitude of the low molecular weight iron pool

Recently we have shown that intracellular low molecular weight (LMW) iron increases during ischemia. It is hypothesized that this increase in LMW iron during ischemia underlies the reported hydrogen peroxide toxicity toward ischemic hearts. To investigate this hypothesis, rat hearts were subjected to 15 min of no-flow ischemia and reperfused with buffer saturated against 95% N2 and 5% CO2 (anoxic reperfusuion) for 7 min. Hearts were then swithched to buffer saturated against 95% O2 and 5% CO2 (reoxygenation) to assess functional recovery. The cardiac function recovered to 80 ± 7% of the preischemic value. When the anoxic reperfusion was applied in the presence of 10 μM hydrogen peroxide, functional recovery after reoxygenation was 47 ± 7%. Hearts that were perfused with deferoxamine before ischemia and then subjected to ischemia and anoxic reperfusion in the presence of 10 μM hydrogen peroxide recovered to 78 ± 8%. Immediate reoxygenation after ischemia led to only 45 ± 6% recovery of function. During ischemia, LMW iron increased from 49 ± 45 to 183 ± 45 pmol/mg protein (p < .05) and decreasedto 58 ± 38 pmol/mg protein (p < .05) during the subsequent anoxic perfusion. Rat hearts preloaded with deferoxamine showed a slightly higher LMW iron content than normal (85 ± 23 and 49 ± 45 pmol/mg protein, respectively; n.s.), which showed a small, nonsignificant increase up to 136 ± 42 pmol/mg protein after 15 min of ischemia. No significant changes were found in reduced and oxidized glutathione content and glutathione peroxidase or catalase activities under those conditions. Our results indicate that hydrogen peroxide toxicity is determined by the amount of catalytic iron in the LMW pool and not by a decrease in antioxidant defense capacity to hydrogen peroxide

Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid

Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals. Copyrigh

Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo

The present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals (.OH) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA) formation from the reaction of salicylate with .OH, of which 2,3-DHBA is a nonenzymatic adduct. Following intrastriatal Mn2+ injection, marked 2,3-DHBA increases were observed in a time- and dose-dependent fashion reaching maximum levels at 6-18 h and a plateau beyond 0.4 μmol (fourfold increase). The delayed increase of 2,3-DHBA levels suggests that Mn2+ induces OH formation in the living brain by an indirect process. The early DA depletion (2 h) and relatively late .OH formation (6 h) indicate independent processes by Mn2+. In addition, depletion of DA (about 90%) by reserpine pretreatment did not significantly alter Mn2+-induced 2,3-DHBA formation or the extent of DA depletion, suggesting that DA or DA autoxidation are not participating in Mn2+-induced .OH formation in vivo. Furthermore, Mn2+ injection did not significantly alter the low molecular weight iron pool in striatum, and co-injections of the iron-chelator deferoxamine with Mn2+ into striatum did not significantly attenuate Mn2+-induced 2,3-DHBA formation. These findings suggest no role of chelatable iron in generation of Mn2+-induced .OH, but do not exclude a role for mitochondrial heme-iron or peroxynitrite (Fe-independent) in Mn2+-induced .OH formation

Factors influencing pharmacists' clinical decision making in pharmacy practice

BackgroundPharmacists’ clinical decision-making is considered a core process of pharmaceutical care in pharmacy practice, but little is known about the factors influencing this process.ObjectiveTo identify factors influencing clinical decision-making among pharmacists working in pharmacy practice.MethodsSemi-structured interviews were conducted with pharmacists working in primary, secondary, and tertiary care settings in the Netherlands between August and December 2021. A thematic analysis was conducted using an inductive approach. The emerged themes were categorized into the Capability–Opportunity-Motivation–Behaviour (COM-B) model domains.ResultsIn total, 16 pharmacists working in primary care (n = 7), secondary care (n = 4) or tertiary care (n = 5) were interviewed. Factors influencing pharmacists' capability to make clinical decisions are a broad theoretical knowledge base, clinical experience, and skills, including contextualizing data, clinical reasoning, and clinical judgment. The pharmacy setting, data availability, rules and regulations, intra- and interprofessional collaboration, education, patient perspectives, and time are mentioned as factors influencing their opportunity. Factors influencing pharmacists’ motivation are confidence, curiosity, critical thinking, and responsibility.ConclusionsThe reported factors covered all domains of the COM-B model, implying that clinical decision-making is influenced by a combination of pharmacists' capability, opportunity, and motivation. Addressing these different factors in pharmacy practice and education may improve pharmacists’ clinical decision-making, thereby improving patient outcomes.</p

Myocardial malondialdehyde and uric acid release after short-lasting coronary occlusion during coronary angioplasty: potential mechanisms for free radical generation

-

Point symmetries in the Hartree-Fock approach: Symmetry-breaking schemes

We analyze breaking of symmetries that belong to the double point group D2h(TD) (three mutually perpendicular symmetry axes of the second order, inversion, and time reversal). Subgroup structure of the D2h(TD) group indicates that there can be as much as 28 physically different, broken-symmetry mean-field schemes --- starting with solutions obeying all the symmetries of the D2h(TD) group, through 26 generic schemes in which only a non-trivial subgroup of D2h(TD) is conserved, down to solutions that break all of the D2h(TD) symmetries. Choices of single-particle bases and the corresponding structures of single-particle hermitian operators are discussed for several subgroups of D2h(TD).Comment: 10 RevTeX pages, companion paper in nucl-th/991207