Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models

Background: Early revascularization of ischemic organs is key to improving outcomes, yet consequent reperfusion injury may be harmful. Reperfusion injury is largely attributed to excess mitochondrial production of reactive oxygen species (ROS). Sulfide inhibits mitochondria and reduces ROS production. Ammonium tetrathiomolybdate (ATTM), a copper chelator, releases sulfide in a controlled and novel manner, and may offer potential therapeutic utility. Methods and findings: In vitro, ATTM releases sulfide in a time-, pH-, temperature-, and thiol-dependent manner. Controlled sulfide release from ATTM reduces metabolism (measured as oxygen consumption) both in vivo in awake rats and ex vivo in skeletal muscle tissue, with a superior safety profile compared to standard sulfide generators. Given intravenously at reperfusion/resuscitation to rats, ATTM significantly reduced infarct size following either myocardial or cerebral ischemia, and conferred survival benefit following severe hemorrhage. Mechanistic studies (in vitro anoxia/reoxygenation) demonstrated a mitochondrial site of action (decreased MitoSOX fluorescence), where the majority of damaging ROS is produced. Conclusions: The inorganic thiometallate ATTM represents a new class of sulfide-releasing drugs. Our findings provide impetus for further investigation of this compound as a novel adjunct therapy for reperfusion injury

Fear of falling in older adults living at home: associated factors

Abstract OBJECTIVE To identify the factors associated with the fear of falling in the older adultliving at home. METHOD Cross-sectional study with probabilistic sampling of older adultenrolled in two Family Health Strategies (FHS). The fear of falling was measured by the Brazilian version of the Falls Efficacy Scale-International and by a household questionnairethat contained the explanatory variables. Multiple Linear Regression using the stepwise selection technique and the Generalized Linear Models were used in the statistical analyses. RESULTS A total of170 older adultsparticipated in the research, 85 from each FHS. The majority (57.1%) aged between 60 and 69; 67.6% were female; 46.1% fell once in the last year. The majority of the older adults(66.5%) had highfear of falling. In the final multiple linear regression model, it was identified that a higher number of previous falls, female gender, older age, and worse health self-assessment explained 37% of the fear of falling among the older adult. CONCLUSION The findings reinforce the need to assess the fear of falling among the older adultliving at home, in conjunction with the development and use ofstrategies based on modifiable factors by professionalsto reduce falls and improve health status, which may contribute to the reduction of the fear of falling among the older adult