RESUMEN
All four serotypes of dengue virus (DENV) cause the full spectrum of disease. Therefore, vaccines must protect against all serotypes. To evaluate candidate vaccines, a human challenge model of dengue serotype 3 (rDEN30Δ30) was developed. All challenge virus recipients safely met the primary endpoint of viremia and secondary endpoints of rash and seroconversion to DENV-3.
RESUMEN
We report the first instance of macrolide resistance developing in vivo following appropriate antibiotic use in a healthy volunteer as a part of a controlled human infection with Campylobacter jejuni. In vivo development of macrolide resistance may be an important contributor to antibiotic resistance in C. jejuni.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Campylobacter/tratamiento farmacológico , Campylobacter jejuni/efectos de los fármacos , Farmacorresistencia Bacteriana , Macrólidos/farmacología , Macrólidos/uso terapéutico , Técnicas de Tipificación Bacteriana , Infecciones por Campylobacter/microbiología , Campylobacter jejuni/clasificación , Campylobacter jejuni/genética , Campylobacter jejuni/aislamiento & purificación , Dermatoglifia del ADN , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Voluntarios Sanos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Adulto JovenRESUMEN
Measurement of skin blood flow is a sensitive marker of C-fiber neurovascular dysfunction. It precedes development of abnormalities in diabetes mellitus, correlates with in vivo indices of the metabolic syndrome, and may be a "benchmark" for future studies on agents to improve microvascular dysfunction in diabetes mellitus. Skin blood flow can be measured under basal and stimulated conditions. There are different methods of evaluation. Iontophoresis and microdialysis are novel methods of drug delivery and the latter may be used as a means of extracting analytes in the skin. Theses methods are not invasive (iontophoresis) or minimally invasive (microdialysis). They can be performed repeatedly and safely in most patients. The use of microdialysis may be limited by sampling only water-soluble molecules. An alternative to microdialysis is iontophoresis, which works better with polar molecules. A combination of microdialysis and iontophoresis techniques can be useful in assessment of the pharmacokinetics of polar and nonpolar agents and the physiology and pathophysiology of the skin neurovascular system.
Asunto(s)
Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Microcirculación/fisiopatología , Humanos , Iontoforesis/métodos , Flujometría por Láser-Doppler , Microdiálisis/métodos , Flujo Sanguíneo Regional/efectos de los fármacos , Reproducibilidad de los Resultados , Piel/irrigación sanguínea , Vasoconstrictores , VasodilatadoresRESUMEN
The physical and chemical processes that lead to the preferential escape of hydrogen over deuterium in the Martian atmosphere are studied in detail using a one-dimensional photochemical model. Comparison of our theory with recent observations of HDO suggests that, averaged over the planet, Mars contains 0.2 m of crustal water that is exchangeable with the atmosphere. Our estimate is considerably lower than recent estimates of subsurface water on Mars based on geomorphological analysis of Viking images. The estimate can be reconciled if only a small fraction of crustal water can exchange with the atmosphere.