RESUMEN
Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust has raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is one of the exposure routes of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFRs and PBDEs in indoor dust are associated with the development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE - Barn, Allergy, Milieu Stockholm Epidemiology). We analyzed the concentrations of 7 PFRs and 21 PBDEs in dust collected around 2 months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP⪢TPHP>mmp-TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE-209⪢BDE-99>BDE-47>BDE-153>BDE-183>BDE-100. There was no positive association between the FRs in mattress dust and the development of childhood asthma. In contrast, dust collected from mattresses of the mothers of children who would develop asthma contained significant lower levels of TPHP and mmp-TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children.
Asunto(s)
Contaminación del Aire Interior/análisis , Asma/etiología , Polvo/análisis , Exposición a Riesgos Ambientales/análisis , Retardadores de Llama/análisis , Contaminación del Aire Interior/efectos adversos , Asma/epidemiología , Ropa de Cama y Ropa Blanca , Estudios de Casos y Controles , Niño , Preescolar , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Éteres Difenilos Halogenados/análisis , Humanos , Masculino , Organofosfatos/análisis , Estudios ProspectivosRESUMEN
BACKGROUND: The initial immune response to house dust mite (HDM) is orchestrated by an interplay between epithelial cells (ECs) and dendritic cells (DCs). Innate cytokines released by HDM-exposed ECs activate airway DCs and effector inflammatory cells, which together induce a HDM-specific Th2 cell response. Here, we investigate the respective roles of DCs and IL-33 in sensitization to HDM. METHOD: Balb/c mice were exposed via the airways to different HDM extracts, differing in at least endotoxin levels [Lotox (LT) and HiTox (HT)]. Alternatively, HDM-pulsed DCs in the presence or absence of additional LT-HDM, or administration of LT-HDM plus recombinant IL-33, were intratracheally (i.t.) administered to induce allergic airway inflammation. Eosinophil recruitment, cytokine production, serum immunoglobulins, and airway histology were analyzed. RESULTS: Direct exposure of airways with HT-HDM induced an eosinophilic airway inflammation, Th2 cytokine production, and an increase in total IgE and HDM IgG1, while LT-HDM was not able to do so. In contrast, i.t. instillation of LT-HDM-pulsed DCs induced a similar airway inflammation, mucus production, and cytokine production, but IgE or HDM IgG1 was not induced. Administration of HDM-pulsed DCs together with LT-HDM, to supply B cells with unprocessed antigen, was not sufficient to induce antibody production. Simultaneous administration of recombinant IL-33 with LT-HDM induced an antibody response, besides a cellular immune response. CONCLUSION: These results demonstrate that HDM-pulsed DCs were able to drive a Th2 response but that IL-33 was needed to induce a humoral immune response to a single inhalational challenge to HDM.
Asunto(s)
Asma/inmunología , Células Dendríticas/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Interleucina-33/inmunología , Alérgenos/inmunología , Animales , Asma/etiología , Citocinas/inmunología , Dermatophagoides pteronyssinus/inmunología , Modelos Animales de Enfermedad , Femenino , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Th2/inmunologíaRESUMEN
BACKGROUND: The mechanism by which many monosensitized allergic individuals progress to polysensitization over time remains to be elucidated. Mouse models have contributed greatly to the understanding of sensitization to inhaled allergens in healthy airways but hardly any studies have addressed sensitization during established allergy. We hypothesized that an allergic inflammatory milieu might facilitate sensitization to inhaled allergens by the presence of mature dendritic cells (DCs) and IL-4. METHODS: Mice with house dust mite (HDM)-induced allergic airway inflammation received a single intratracheal dose of ovalbumin (OVA), 2 days after the last HDM exposure. Ten days later, sensitization was assessed by rechallenge with OVA. We evaluated the following factors for their importance in neosensitization: (1) maturation and recruitment of DCs to the airways, (2) dependency on DCs using CD11cDTR conditional knockout mice, (3) presence of ongoing airway inflammation by comparing sensitization at day 2 and day 14 after the last HDM exposure and (4) dependency on IL-4 by treatment with blocking antibodies. RESULTS: House dust mite -induced inflammation facilitated neosensitization to OVA. HDM-induced inflammation increased the number of airway DCs with a mature phenotype but a DC reduction of 93% did not inhibit sensitization. Neosensitization to OVA was dependent on ongoing inflammation and in particular on IL-4. CONCLUSIONS: These findings show that HDM-induced allergic airway inflammation facilitates neosensitization to a second inhaled allergen in an IL-4-dependent manner and provide insight into the underlying mechanism of the frequently observed progression to polysensitization in HDM-monosensitized individuals.
Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Hipersensibilidad/etiología , Pyroglyphidae/inmunología , Administración por Inhalación , Animales , Antígeno CD11c/análisis , Células Dendríticas/fisiología , Femenino , Interleucina-4/fisiología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunologíaRESUMEN
The electrooxidative behavior and determination of zolmitriptan at a boron-doped diamond electrode were investigated using cyclic, linear sweep, differential pulse and square wave voltammetric techniques. Zolmitriptan undergoes irreversible oxidation at a peak potential of about +0.9 V (vs Ag/AgCl/3 M KCl). DPV and SWV techniques are proposed for the determination of zolmitriptan in phosphate buffer at pH 3.03, which allows quantitation over the two different ranges (8 x 10(-7) - 8 x 10(-6) M and 1 x 10(-5) - 1 x 10(-4) M) in supporting electrolyte for both methods. A linear response was obtained in phosphate buffer over two different ranges (6 x 10(-7) - 8 x 10(-6) M and 1 x 10(-5) - 1 x 10(-4) M) for spiked serum samples at pH 3.03 for both techniques. The repeatability and reproducibility of the methods for all media were determined. The standard addition method was used in serum. Precision and accuracy were also checked in all media. No electroactive interferences from the excipients and endegenous substances were found in the pharmaceutical dosage form and the biological sample, respectively.
Asunto(s)
Oxazolidinonas/química , Agonistas de Receptores de Serotonina/química , Triptaminas/química , Algoritmos , Boro/química , Calibración , Diamante , Electroquímica , Electrodos , Humanos , Indicadores y Reactivos , Oxazolidinonas/sangre , Estándares de Referencia , Reproducibilidad de los Resultados , Agonistas de Receptores de Serotonina/sangre , Comprimidos , Triptaminas/sangreRESUMEN
Indinavir sulfate is an inhibitor of the human immunodeficiency virus (HIV) protease. The aim of this study was to determine indinavir levels in serum and pharmaceuticals, by means of electrochemical methods using the hanging mercury drop electrode (HMDE). Indinavir exhibited irreversible cathodic waves over the pH range 2.00-12.00 in different supporting electrolytes. The current-concentration plot was rectilinear over the range from 8 x 10(-7) M to 8 x 10(-6) M with a correlation coefficient of 0.996 for differential pulse voltammetry (DPV) and 8 x 10(-7) M to 1 x 10(-5) M with correlation of 0.999 M for osteryoung square ware voltammetry (OSWV) in Britton-Robinson buffer at pH 10.00. The wave was characterized as being irreversible and diffusion-controlled. The proposed methods were fully validated and successfully applied to the determination of indinavir in capsules and spiked human serum samples with good recoveries. The repeatability and reproducibility of the methods as well as precision and accuracy (such as supporting electrolyte, serum samples) were determined. No electroactive interferences from the endogenous substances were found in serum samples.