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1.
Nat Commun ; 12(1): 5233, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34475387

RESUMEN

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication.


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Sarampión/prevención & control , Morfolinas/uso terapéutico , Piperidinas/uso terapéutico , Pirazoles/uso terapéutico , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , Animales , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacocinética , Tolerancia Inmunológica/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Virus del Sarampión/efectos de los fármacos , Morfolinas/farmacocinética , Piperidinas/farmacocinética , Pirazoles/farmacocinética , Saimiri , Replicación Viral/efectos de los fármacos , Esparcimiento de Virus/efectos de los fármacos
2.
Artículo en Inglés | MEDLINE | ID: mdl-34077339

RESUMEN

Probabilistic exposure and risk assessment of chemical hazards in the diet have increasingly gained ground in recent years as a pragmatic approach for the approximation of reality. This work presents the outcomes of a project which aimed at applying probabilistic techniques for basic modelling of chronic dietary exposure to food contaminants following EFSA guidance. These techniques, based on Monte Carlo Risk Assessment (MCRA) software and on the programming language R, were employed for the risk assessment of cadmium for Austrian adults, enabling the validation and the critical comparison of the two approaches. Harmonisation and optimisation of procedures, refinement of exposure assessment skills and confidence in the results were the main benefits. Data amount and validity were identified as critical parameters, influencing the precision of the results. Cadmium was selected as a case study due to its toxicological properties, its ubiquitous presence in food and the availability of Austrian occurrence data. Similar exposure and risk estimates were generated through MCRA and R in alternative optimistic and pessimistic exposure scenarios, suggesting low levels of concern, except for vegetarians, whose upper tail exposures are close to the established Tolerable Weekly Intake. However, as occurrence data gaps have been identified as the major element of uncertainty, the estimated exposure and risk levels are characterised as underestimated. Grains and grain-based products, potatoes and leafy vegetables are the main contributors to the intake. The results will contribute to risk management and to a future refinement of the assessment.


Asunto(s)
Cadmio/efectos adversos , Exposición Dietética/estadística & datos numéricos , Contaminación de Alimentos/análisis , Medición de Riesgo/métodos , Gestión de Riesgos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Austria , Dieta/estadística & datos numéricos , Exposición Dietética/efectos adversos , Grano Comestible/química , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Método de Montecarlo , Vigilancia de la Población , Programas Informáticos , Solanum tuberosum/química , Verduras/química
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