RESUMO
Impaired intestinal barrier function occurs before type 1 diabetes (T1D) onset with a possible contribution of microbial translocation. Breastfeeding is associated with enhanced mucosal intestinal integrity and T1D protection. Our aim was to study the potential of human milk (HM) to prevent diabetes onset and modulate the translocation of gut bacteria susceptible to breastfeeding or associated to diabetes onset. We show that HM intake can prevent T1D in nonobese diabetic mice independently of bifidobacteria colonization. Prior to diabetes onset, HM mice harbored splenic bacterial counts and plasma lipopolysaccharides level similar to control mice but exhibited a reduced expansion of Anaerotruncus sp. in pancreas and Lactobacillus johnsonii and Barnesiella in Peyer's patches (PP). Surprisingly, pancreas and PP bacterial expansion did not correlate with their own gut localization but with ileal Escherichia coli and cecal HM-susceptible bacteria (the promoted L. murinus and Bacteroides vulgatus, and the repressed B. fragilis and E. coli), respectively. Besides, higher colonic B. vulgatus counts induced by HM intake were associated with low islet infiltration and pancreatic E. coli expansion. On another hand, splenic dendritic cells (DCs) were identified as negative covariate of PP Barnesiella, suggesting a possible HM contribution to preserving splenic DCs through the reduction of Barnesiella translocation. Fecal B. vulgatus also negatively correlated with PP Barnesiella expansion, indicating that the mouse coprophagic behavior likely added to HM effect. Our findings provide evidence that HM has a multilevel impact and cooperates with some gut bacteria for controlling bacterial translocation at the earliest stage of insulitis.
Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Leite Humano , Animais , Bifidobacterium/fisiologia , Colo/microbiologia , Diabetes Mellitus Tipo 1/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos NOD , Pâncreas/microbiologia , Nódulos Linfáticos Agregados/microbiologia , Verrucomicrobia/fisiologiaRESUMO
Infectious agents including viruses are thought to play a role in the pathogenesis of necrotizing enterocolitis, a well-known gastrointestinal emergency in newborns. Enteroviruses are common pathogens in neonates and have been associated with outbreaks in neonatal units. Enterovirus-associated necrotizing enterocolitis has been described in 3 preterms. Spatiotemporal and molecular analyses have provided evidence of nosocomial transmission.
Assuntos
Infecção Hospitalar/complicações , Enterocolite Necrosante/etiologia , Infecções por Enterovirus/complicações , Enterovirus/isolamento & purificação , Infecção Hospitalar/virologia , Surtos de Doenças , Enterocolite Necrosante/diagnóstico , França , Humanos , Recém-Nascido , Doenças do Recém-Nascido/virologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Análise Espaço-TemporalRESUMO
BACKGROUND: Malformations of the cerebral cortex may be associated with severe epilepsy and status epilepticus. It has been shown that status epilepticus models induce excitotoxic cell death. In humans, very few data are available. CASE AND RESULTS: We report a case of a multifocal disorder of the lamination diagnosed in a neonate, born at 30 weeks' gestation, who died from a refractory status epilepticus at two months and half. This abnormality was not detected by repeated MRI studies. Only microscopic investigations permitted to identify this disorder of the lamination. We found also little cell death or cell loss. DISCUSSION: Our report highlights the possible false negative results of MRI in a newborn. We can also discuss that immature human brain maybe less sensitive to neuronal injury than mature as described in animal models.
Assuntos
Encéfalo/anormalidades , Estado Epiléptico/patologia , Estado Epiléptico/fisiopatologia , Animais , Morte Celular , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Estado Epiléptico/mortalidadeRESUMO
Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.
Assuntos
Diferenciação Celular , Proteínas de Ligação a DNA/metabolismo , Insulina/biossíntese , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Fatores de Transcrição/metabolismo , 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 , Análise Mutacional de DNA , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Diabetes Mellitus/congênito , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Embrião de Mamíferos/metabolismo , Feminino , Feto/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Recessivos/genética , Testes Genéticos , Humanos , Recém-Nascido , Ilhotas Pancreáticas/embriologia , Masculino , Camundongos , Células NIH 3T3 , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Especificidade de Órgãos , Fatores de Transcrição de Fator Regulador X , Síndrome , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To test the hypothesis that prophylactic treatment of neutropenic premature neonates with recombinant granulocyte-colony stimulating factor (rG-CSF) would reduce the incidence of nosocomial infections (NIs). STUDY DESIGN: A total of 25 neonatal intensive care units participated in this multicenter, randomized, double-blind, placebo-controlled trial. Premature infants of gestational age (GA) Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
, Doenças do Prematuro/tratamento farmacológico
, Neutropenia/tratamento farmacológico
, Infecção Hospitalar/prevenção & controle
, Método Duplo-Cego
, Feminino
, Idade Gestacional
, Humanos
, Recém-Nascido
, Recém-Nascido Prematuro
, Doenças do Prematuro/diagnóstico
, Recém-Nascido de muito Baixo Peso
, Contagem de Leucócitos
, Masculino
, Neutropenia/diagnóstico
, Proteínas Recombinantes
, Resultado do Tratamento