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1.
PLoS One ; 14(1): e0210064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625189

RESUMO

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.


Assuntos
Transtorno Autístico/tratamento farmacológico , Colostro , Gastroenteropatias/tratamento farmacológico , Probióticos/uso terapêutico , Animais , Transtorno Autístico/fisiopatologia , Bovinos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Gastroenteropatias/fisiopatologia , Humanos , Interleucina-13/metabolismo , Masculino , Prebióticos , Fator de Necrose Tumoral alfa/metabolismo
2.
Toxicol Lett ; 292: 85-96, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29689377

RESUMO

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR-/-) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR-/- BMDCs with autologous naive T cells. PM2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM2.5 induced interleukin (IL)-1ß, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Células Dendríticas/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Material Particulado/toxicidade , Receptores de Hidrocarboneto Arílico/agonistas , Células Th17/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Técnicas de Cocultura , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Hep G2 , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Receptores de Hidrocarboneto Arílico/deficiência , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Elementos de Resposta , Transdução de Sinais/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo
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