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1.
Am J Med Genet A ; 191(11): 2703-2710, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37698299

RESUMO

Congenital heart disease (CHD) is common among patients with trisomy 18 (T18), but cardiac surgery has been rarely indicated for T18 patients due to their short life span. Although the therapeutic effects of aggressive interventions were recently demonstrated for T18 patients, the subjects and factors examined varied, resulting in inconsistent findings. Therefore, the effects of cardiac surgery for T18 remain unclear. We herein investigated the outcomes of cardiac palliative surgery for CHD with increased pulmonary blood flow in T18 patients. 27 patients were examined: 13 (48.1%) underwent cardiac palliative surgery and 14 (51.9%) did not. Median survival times in the no-surgery and surgery groups were 223.0 days (95% confidence interval [CI]: 46-361 days) and 723.0 days (95% CI: 360-1447 days), respectively. The number of patients with pulmonary hypertension significantly differed between the two groups (5 of 14 in the no-surgery group and 0 in the surgery group). Five of 14 patients in the no-surgery group and 10 of 13 in the surgery group were discharged to home care (odds ratio: 10.8 [95% CI: 1.07-110.0]). Therefore, cardiac palliative surgery may be used to treat CHD with increased pulmonary blood flow in T18 patients.

3.
Neurosci Lett ; 653: 296-301, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28595950

RESUMO

Maternal infection during pregnancy increases the risk of neurodevelopmental conditions such as autism spectrum disorders and schizophrenia in offspring. Several previous animal studies have indicated that maternal immune activation (MIA), rather than a specific pathogen, alters fetal brain development. Among them, prenatal exposure to interleukin-6 (IL-6) has been associated with behavioral and neuropathological abnormalities, though such findings remain to be elucidated in humans. We developed a human cell-based model of MIA by exposing human induced pluripotent stem cells (hiPSCs)-derived neural aggregates to IL-6 and investigated whether luteolin-a naturally occurring flavonoid found in edible plants-could prevent MIA-induced abnormalities. We generated neural aggregates from hiPSCs using the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) method, following which aggregates were cultured in suspension. We then exposed the aggregates to IL-6 (100ng/ml) for 24h at day 51. Transient IL-6 exposure significantly increased the area ratio of astrocytes (GFAP-positive area ratio) and decreased the area ratio of early-born neurons (TBR1-positive or CTIP2-positive area ratio) relative to controls. In addition, western blot analysis revealed that levels of phosphorylated STAT3 were significantly elevated in IL-6-exposed neural aggregates. Luteolin treatment inhibited STAT3 phosphorylation and counteracted IL-6-mediated increases of GFAP-positive cells and reductions of TBR1-positive and CTIP2-positive cells. Our observations suggest that the flavonoid luteolin may attenuate or prevent MIA-induced neural abnormalities. As we observed increased apoptosis at high concentrations of luteolin, further studies are required to determine the optimal intake dosage and duration for pregnant women.


Assuntos
Gliose/tratamento farmacológico , Gliose/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Interleucina-6/metabolismo , Luteolina/farmacologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/imunologia , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Feminino , Humanos , Gravidez
4.
Neuroradiology ; 55(10): 1251-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23893073

RESUMO

INTRODUCTION: With reducing mortality in children with hematological malignancies, the survivors' quality of life regarding development of chronic neurological disturbances is important. We aimed to determine whether chemotherapy affects white matter (WM). METHODS: Using brain diffusion tensor imaging, we evaluated 17 patients (15 with acute lymphoblastic leukemia, 2 with non-Hodgkin's lymphoma; 9 male, 8 female; age, 1.6-13 years) before and after chemotherapy. We measured the quantitative values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at the regions of interest (ROIs) such as periventricular WM, corona radiata, posterior limb of the internal capsule, and corpus callosum. We assessed sensorimotor and callosal tracts by tractography. RESULTS: Reduction in FA and increase in ADC were significant at the ROIs of the left and right anterior periventricular WM and corona radiata and at the tract passing through the genu. A significant reduction in FA with a nonsignificant increase in ADC was seen at the ROI of the genu and at the tracts passing through the body and isthmus. CONCLUSION: Chemotherapy in children with hematological malignancies predominantly affects the frontal WM. This finding might indicate a negative effect of chemotherapy on neurological development in children with hematological malignancies.


Assuntos
Antineoplásicos/efeitos adversos , Encefalopatias/induzido quimicamente , Encefalopatias/patologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/patologia , Adolescente , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
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