RESUMO
Background: Legislation has made organ donation after brain death (DBD) possible in India since 1994. However, no organs are donated in most parts of the country; the national organ donation rate is estimated at between 0.08 and 0.34 donors per million population-one of the lowest in the world. Methods: A 350-bedded private hospital in Kochi started its DBD programme in September 2013 with a structured approach based on counselling of family members of critically ill individuals. A counsellor trained to diagnose family dynamics, and recognize different stages of the grieving process, chose the right time, and the correct family member to whom the donation request could be made. Regular debriefing sessions of the core team consisting of a transplant surgeon, a transplant coordinator, an ICU counsellor and a unit administrator resulted in setting up systems that supported families of patients with catastrophic brain injury, and created an environment conducive to obtaining consent. Results: A total of 85 organ donations took place in the first 24 months (September 2013 to September 2015) of instituting the programme. Conclusion: It is possible with hospital-based teamwork and a structured approach to consistently elicit organ donation.
Assuntos
Hospitais Privados/organização & administração , Transplante de Órgãos/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Aconselhamento , Estado Terminal , Família , Feminino , Hospitais Privados/estatística & dados numéricos , Hospitais Privados/tendências , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/legislação & jurisprudência , Transplante de Órgãos/tendências , Avaliação de Programas e Projetos de Saúde , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/tendências , Adulto JovemRESUMO
Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually. The pore-forming cytotoxin, pneumolysin (PLY) is a major virulence factor. Here, we found that recombinant PLY as well as wild-type pneumococcal strains, but not the isogenic PLY mutant, upregulated the shedding of extracellular vesicles (EVs) harboring membrane-bound toxin from human THP-1 monocytes. PLY-EVs induced cytotoxicity and hemolysis dose-dependently upon internalization by recipient monocyte-derived dendritic cells. Proteomics analysis revealed that PLY-EVs are selectively enriched in key inflammatory host proteins such as IFI16, NLRC4, PTX3, and MMP9. EVs shed from PLY-challenged or infected cells induced dendritic cell maturation and primed them to infection. In vivo, zebrafish administered with PLY-EVs showed pericardial edema and mortality. Adoptive transfer of bronchoalveolar-lavage-derived EVs from infected mice to healthy recipients induced lung damage and inflammation in a PLY-dependent manner. Our findings identify that host EVs released during infection mediate pneumococcal pathogenesis.
RESUMO
Effluent produced during the electroplating process can contain high concentrations of heavy metals that can enter the environment and induce toxicity to aquatic organisms. Relatively high concentrations of zinc (Zn) and mercury (Hg) have been detected in treated electroplating industrial effluent (TEPIE), though the cytotoxic potential of these compounds has not been well assessed in fish gills. A novel cell line, Danio rerio gill (DrG), were exposed to TEPIE and concentrations of Zn, Hg, and Zn + Hg previously measured in treated effluent to evaluate the use of the DrG cell line following exposure to environmental pollutants. Several cytotoxic assays were employed to assess the effect of TEPIE, Zn, and Hg on this cell line. The percent cell viability was significantly reduced in a concentration-dependent manner following exposure to TEPIE, Zn, Hg, and Zn + Hg (p < 0.05) for 24 h, with additional morphological changes observed in exposure treatments relative to controls. Additionally, there was a significant induction of DNA damage detected in all exposure treatments determined through comet assay tail length. An increase in intracellular ROS generation was also observed in cells exposed to TEPIE, Zn, Hg, and Zn + Hg, corresponding to dose-dependent increases in apoptosis. Our study confirmed that TEPIE and the metals present in it induced cytotoxicity in the DrG cell line, demonstrating its usefulness as a model to explore relationships between pollutants and fish gills.