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1.
Pediatr Res ; 79(1-2): 227-33, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26460523

ABSTRACT

Adverse childhood experiences (ACEs) are related to short- and long-term negative physical and mental health consequences among children and adults. Studies of the last three decades on ACEs and traumatic stress have emphasized their impact and the importance of preventing and addressing trauma across all service systems utilizing universal systemic approaches. Current developments on the implementation of trauma informed care (TIC) in a variety of service systems call for the surveillance of trauma, resiliency, functional capacity, and health impact of ACEs. Despite such efforts in adult medical care, early identification of childhood trauma in children still remains a significant public health need. This article reviews childhood adversity and traumatic toxic stress, presents epidemiologic data on the prevalence of ACEs and their physical and mental health impacts, and discusses intervention modalities for prevention.


Subject(s)
Wounds and Injuries/physiopathology , Wounds and Injuries/psychology , Adult , Child , Humans , Mental Health , Wounds and Injuries/epidemiology
2.
PLoS Med ; 4(6): e206, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17579510

ABSTRACT

BACKGROUND: Schistosomiasis--infection with helminth parasites in the genus Schistosoma, including S. mansoni--is a widespread, devastating tropical disease affecting more than 200 million people. No vaccine is available, and praziquantel, the only drug extensively utilized, is currently administered more than 100 million people yearly. Because praziquantel resistance may develop it is essential to identify novel drug targets. Our goal was to investigate the potential of a unique, selenium-containing parasite enzyme thioredoxin glutathione reductase (TGR) as a drug target. METHODS AND FINDINGS: Using RNA interference we found that TGR is essential for parasite survival; after silencing of TGR expression, in vitro parasites died within 4 d. We also found that auranofin is an efficient inhibitor of pure TGR (Ki = 10 nM), able to kill parasites rapidly in culture at physiological concentrations (5 microM), and able to partially cure infected mice (worm burden reductions of ~60%). Furthermore, two previously used antischistosomal compounds inhibited TGR activity, suggesting that TGR is a key target during therapy with those compounds. CONCLUSIONS: Collectively, our results indicate that parasite TGR meets all the major criteria to be a key target for antischistosomal chemotherapy. To our knowledge this is the first validation of a Schistosoma drug target using a convergence of both genetic and biochemical approaches.


Subject(s)
Multienzyme Complexes/antagonists & inhibitors , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/prevention & control , Schistosomicides/therapeutic use , Animals , Auranofin/pharmacology , Auranofin/therapeutic use , Drug Design , Female , Kinetics , Male , Mice , Mice, Inbred C57BL , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , NADH, NADPH Oxidoreductases/genetics , NADH, NADPH Oxidoreductases/metabolism , Naphthoquinones/pharmacology , Naphthoquinones/therapeutic use , Oxidation-Reduction , RNA Interference , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/metabolism , Schistosoma mansoni/enzymology , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/parasitology , Schistosomicides/pharmacology , Signal Transduction/drug effects
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