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1.
Psychoneuroendocrinology ; 122: 104883, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33027708

RESUMO

Premature birth is a traumatic event that puts mother and child at risk for subsequent psychopathology. Skin-to-skin contact in the form of intermittent kangaroo mother care has been shown to positively affect the infant's stress response and cognitive development, but underlying mechanisms remain unclear. Moreover, first skin-to-skin contact is usually delayed for days after birth. In the delivery room skin-to-skin study (DR-SSC), a prospective randomized controlled trial conducted from 2/2012 to 7/2015, we set out to assess the effect of delivery room skin-to-skin contact on the infant's mRNA expression of six key molecules involved in stress response and neurobehavioral development at hospital discharge. 88 firstborn, singleton preterm infants (born at 25-32 weeks of gestational age) were included. In the delivery room after initial stabilization, infants were randomized to either 60 min of skin-to-skin or 5 min of visual contact with their mother. In this explorative add-on study on the original DR-SSC study, we determined the expression of six important stress response genes (CRHR1 and CRHR2, AVP, NR3C1, HTR2A, and SLC6A4) in peripheral white blood cells of infants during routine blood sampling upon hospital discharge (corrected gestational age of 40 weeks). Infants were followed up to six months corrected age. Relative mRNA expression of the corticotropin releasing hormone receptor 2 (CRH R2), the glucocorticoid receptor gene (NR3C1), and the serotonin transporter gene (SLC6A4) was significantly reduced in the delivery room SSC infants. Additionally, gene expression of CRH R2 showed a correlation with HPA axis reactivity and parameters of mother-child interaction at six months corrected age. Our results highlight the importance of delivery room mother-child skin-to-skin contact and underline the urgent need for in-depth studies on the underlying molecular mechanisms.


Assuntos
Recém-Nascido Prematuro/psicologia , Método Canguru/psicologia , Estresse Fisiológico/genética , Desenvolvimento Infantil/fisiologia , Salas de Parto , Feminino , Idade Gestacional , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Unidades de Terapia Intensiva Neonatal , Método Canguru/métodos , Relações Mãe-Filho , Mães/psicologia , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Nascimento Prematuro , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Glucocorticoides/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Pele , Estresse Fisiológico/fisiologia , Tato/fisiologia
2.
J Mol Med (Berl) ; 98(3): 395-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008055

RESUMO

This study was performed to identify transcriptional alterations in male intrauterine growth restricted (IUGR) rats during and at the end of nephrogenesis in order to generate hypotheses which molecular mechanisms contribute to adverse kidney programming. IUGR was induced by low protein (LP) diet throughout pregnancy, bilateral uterine vessel ligation (LIG), or intrauterine stress (IUS) by sham operation. Offspring of unimpaired dams served as controls. Significant acute kidney damage was ruled out by negative results for proteins indicative of ER-stress, autophagy, apoptosis, or infiltration with macrophages. Renal gene expression was examined by transcriptome microarrays, demonstrating 53 (LP, n = 12; LIG, n = 32; IUS, n = 9) and 134 (LP, n = 10; LIG, n = 41; IUS, n = 83) differentially expressed transcripts on postnatal days (PND) 1 and 7, respectively. Reduced Pilra (all IUGR groups, PND 7), Nupr1 (LP and LIG, PND 7), and Kap (LIG, PND 1) as well as increased Ccl20, S100a8/a9 (LIG, PND 1), Ifna4, and Ltb4r2 (IUS, PND 7) indicated that inflammation-related molecular dysregulation could be a "common" feature after IUGR of different origins. Network analyses of transcripts and predicted upstream regulators hinted at proinflammatory adaptions mainly in LIG (arachidonic acid-binding, neutrophil aggregation, toll-like-receptor, NF-kappa B, and TNF signaling) and dysregulation of AMPK and PPAR signaling in LP pups. The latter may increase susceptibility towards obesity-associated kidney damage. Western blots of the most prominent predicted upstream regulators confirmed significant dysregulation of RICTOR in LP (PND 7) and LIG pups (PND 1), suggesting that mTOR-related processes could further modulate kidney programming in these groups of IUGR pups. KEY MESSAGES: Inflammation-related transcripts are dysregulated in neonatal IUGR rat kidneys. Upstream analyses indicate renal metabolic dysregulation after low protein diet. RICTOR is dysregulated after low protein diet and uterine vessel ligation.


Assuntos
Retardo do Crescimento Fetal/genética , Rim/metabolismo , Animais , Animais Recém-Nascidos , Rim/crescimento & desenvolvimento , Masculino , Tamanho do Órgão , Ratos Wistar , Transcriptoma
3.
Paediatr Drugs ; 21(2): 95-106, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30941653

RESUMO

Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in phase III trials (denosumab, vosoritide, palovarotene). To offer a multi-disciplinary therapeutic approach, it is recommended that patients with rare skeletal disorders are treated and monitored in highly specialized centers. This guarantees the greatest safety for the individual patient and offers the possibility of collecting data to further improve treatment strategies for these rare conditions. Additionally, new therapeutic options could be achieved through increased awareness, not only in the field of pediatrics but also in prenatal and obstetric specialties. Presenting new therapeutic options might influence families in their decision of whether or not to terminate a pregnancy with a child with a skeletal disease.


Assuntos
Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Raras/tratamento farmacológico , Fosfatase Alcalina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Criança , Denosumab/uso terapêutico , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Mutação , Gravidez , Pirazóis/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Estilbenos/uso terapêutico
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