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

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods

Objetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.Objetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.Objective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous