Acute exposure to imidazoline derivatives in children

OBJECTIVES: To study acute exposure to imidazoline derivatives in 72 children younger than 15 years of age, followed-up from January 1994 to December 1999. METHODS: This is a retrospective study of 72 patients with age between 2 months and 13 years (median 2 years; 25-75% = 1 to 3 years old) exposed to naphazoline (N=48), fenoxazoline (N=18), oxymetazoline (N=5) and tetrahydrozoline (N=1), through oral (N=46), nasal (N=24) or unknown (N=2) routes. RESULTS: Fifty-seven children developed clinical manifestations such as somnolence (N=34/57), sweating (N=20/57), pallor (N=17/57), hypothermia (N=16/57), bradycardia (N=13/57), cool extremities (N=9/57), restlessness (N=7/57), tachycardia (N=6/57), vomiting (N= 5/57), irregular respiratory pattern and apnea (N= 5/57), miosis/mydriasis (N=4/57). Naphazoline was the active ingredient most frequently involved (N=47), followed by phenoxazoline (N=5) and oxymetazoline (N=4). The onset of clinical manifestations was rapid, beginning within 2 hours after exposure in 32/57 children. Only supportive measures were employed, with one child requiring mechanical ventilation after accidental naphazoline ingestion. In most of the children resolution of symptoms occurred within 24 hours (N= 39/57). No deaths were observed. Patients exposed to naphazoline (N=47/48) presented a higher frequency of clinical signs of poisoning in comparison with those exposed to phenoxazoline (N= 5/18) (p < 0.001). There were no significant differences in the frequency of patients who presented clinical manifestations considering the route of exposure [oral (N=34/46), nasal (N=21/24); p=0.31]. CONCLUSIONS: Most children (especially those younger than 3 years) exposed to imidazoline derivatives (especially naphazoline) presented early signs of poisoning regardless of the exposure route (nasal or oral). The main signs observed were nervous system, cardiovascular and respiratory depression. Most children showed complete resolution of the symptoms within 24 hours.OBJETIVOS: Estudar a exposição aguda a derivados imidazolínicos em crianças com idade inferior a 15 anos, atendidas no período de janeiro de 1994 a dezembro de 1999. MÉTODOS: Neste estudo retrospectivo foram avaliadas 72 crianças com idades entre dois meses e 13 anos, mediana de dois anos (25% a 75%; um a três anos), expostas a nafazolina (n = 48), fenoxazolina (n = 18), oximetazolina (n = 5) e tetrizolina (n = 1); por via oral (n = 46), nasal (n = 24) ou desconhecida (n = 2). RESULTADOS: No total, 57 crianças desenvolveram manifestações clínicas: sonolência (n = 34), sudorese (n = 20), palidez (n = 17), hipotermia (n = 16), bradicardia (n = 13), extremidades frias (n = 9), agitação (n = 7), taquicardia (n = 6), vômitos (n = 34), respiração irregular e apnéia (n = 5), miose/midríase (n = 4), sendo a nafazolina (n = 47), a fenoxazolina (n = 5) e a oximetazolina (n = 4) os princípios ativos mais envolvidos. O início das manifestações clínicas foi rápido, iniciando-se, em 32/57 crianças, até duas horas após a exposição. Somente medidas de suporte foram empregadas, com uma criança necessitando de ventilação mecânica após exposição à nafazolina. Na maioria dos pacientes, o quadro clínico remitiu até 24 horas após a exposição (n = 39/57). Não houve evolução letal. Pacientes expostos à nafazolina (n = 47/48) apresentaram maior freqüência de manifestações clínicas de intoxicação em comparação com aqueles expostos à fenoxazolina (n = 5/18) (p < 0,001). Comparando-se a freqüência de pacientes que desenvolveram manifestações clínicas de acordo com a via de exposição (oral, n = 34/46; nasal, n = 21/24), não foi encontrada uma diferença estatisticamente significante (p = 0,31). CONCLUSÕES: Na maioria dos casos de exposição a derivados imidazolínicos, principalmente à nafazolina e em crianças com menos de três anos de idade, ocorreu, independentemente da via (oral ou nasal), o aparecimento precoce de manifestações clínicas de intoxicação, destacando-se as depressões neurológica, cardiovascular e respiratória, que regrediram até 24 horas após a exposição.519524Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Exposição aguda a derivados imidazolínicos em crianças

OBJETIVOS: Estudar a exposição aguda a derivados imidazolínicos em crianças com idade inferior a 15 anos, atendidas no período de janeiro de 1994 a dezembro de 1999. MÉTODOS: Neste estudo retrospectivo foram avaliadas 72 crianças com idades entre dois meses e 13 anos, mediana de dois anos (25% a 75%; um a três anos), expostas a nafazolina (n = 48), fenoxazolina (n = 18), oximetazolina (n = 5) e tetrizolina (n = 1); por via oral (n = 46), nasal (n = 24) ou desconhecida (n = 2). RESULTADOS: No total, 57 crianças desenvolveram manifestações clínicas: sonolência (n = 34), sudorese (n = 20), palidez (n = 17), hipotermia (n = 16), bradicardia (n = 13), extremidades frias (n = 9), agitação (n = 7), taquicardia (n = 6), vômitos (n = 34), respiração irregular e apnéia (n = 5), miose/midríase (n = 4), sendo a nafazolina (n = 47), a fenoxazolina (n = 5) e a oximetazolina (n = 4) os princípios ativos mais envolvidos. O início das manifestações clínicas foi rápido, iniciando-se, em 32/57 crianças, até duas horas após a exposição. Somente medidas de suporte foram empregadas, com uma criança necessitando de ventilação mecânica após exposição à nafazolina. Na maioria dos pacientes, o quadro clínico remitiu até 24 horas após a exposição (n = 39/57). Não houve evolução letal. Pacientes expostos à nafazolina (n = 47/48) apresentaram maior freqüência de manifestações clínicas de intoxicação em comparação com aqueles expostos à fenoxazolina (n = 5/18) (p < 0,001). Comparando-se a freqüência de pacientes que desenvolveram manifestações clínicas de acordo com a via de exposição (oral, n = 34/46; nasal, n = 21/24), não foi encontrada uma diferença estatisticamente significante (p = 0,31). CONCLUSÕES: Na maioria dos casos de exposição a derivados imidazolínicos, principalmente à nafazolina e em crianças com menos de três anos de idade, ocorreu, independentemente da via (oral ou nasal), o aparecimento precoce de manifestações clínicas de intoxicação, destacando-se as depressões neurológica, cardiovascular e respiratória, que regrediram até 24 horas após a exposição

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