In an accident involving the stealing and breaching of a radiotherapy source in Goiânia, Brazil, 39 individuals had a high level of 137Cs internal contamination. Prussian Blue was used, in doses that varied from 3-10 g d-1 for adults, to enhance the elimination of 137Cs from the body. The total internal committed doses and the effect of Prussian Blue treatment for 15 contaminated adults involved in this accident have been evaluated in this paper. Prussian Blue caused dose reductions in the range of 51-84%, with an average of 71%. This reduction was shown to be independent of the dosage of Prussian Blue. Total internal committed doses were in the range of 4.6 x 10(-3) Gy to 9.7 x 10(-1) Gy for the most-contaminated adults. Data on 137Cs biological half-lives for seven children contaminated in the accident are also presented.
Human cytomegalovirus (HCMV) is a pathogenic agent responsible for morbidity and mortality in immunocompromised and immunosuppressed individuals. HCMV encodes a serine protease that is essential for the production of infectious virions. In this work, we applied molecular dynamics (MD) simulations on HCMV protease models in order to investigate the experimentally observed (i) catalytic activity of the enzyme homodimer and (ii) induced-fit mechanism upon the binding of substrates and peptidyl inhibitors. Long and stable trajectories were obtained for models of the monomeric and dimeric states, free in solution and bound covalently and noncovalently to a peptidyl-activated carbonyl inhibitor, with very good agreement between theoretical and experimental results. The MD results suggest that HCMV protease indeed operates by an induced-fit mechanism. Also, our analysis indicates that the catalytic activity of the dimer is a result of more favorable interactions between the oxyanion in the covalently bound state and the backbone nitrogen of Arg165, resulting in a reaction that is 7.0 kcal/mol more exergonic and a more significant thermodynamic driving force. The incipient oxyanion in the transition state should also benefit from the stronger interactions with Arg165, reducing in this manner the intrinsic activation barrier for the reaction in the dimeric state.
Introduction: Tinnitus is a complex disorder of hearing and, in its most common form, is presented as a phantom auditory sensation which is not associated with an external sound stimulus. The sudden hearing loss is often characterized by an abrupt idiopathic onset. In up to 80% of these patients tinnitus is present and becomes the main complaint. In this research corticosteroids are the used therapy for sudden hearing loss.
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