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1.
Biomed Pharmacother ; 128: 110045, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32460187

RESUMO

Ischemic stroke is a major cause of death and disability worldwide. Necroptosis is known as a form of cell death, playing an essential role in regulating ischemia-induced brain injury. Triad3A is a ubiquitin ligase of the RING-in-between-RING family, and regulates necroptotic cell death under different pathological conditions, including neurodegenerative disorders. In the present study, the effects of Triad3A on experimental stroke were explored on a mouse model with middle cerebral artery occlusion (MCAO). The results indicated that Triad3A expression was markedly induced in the ischemic brain after MCAO operation. The neurons and microglia cells were the major cellular sources for Triad3A induction. Triad3A knockdown enhanced the infarction area, cell death, microglia activity, and the expression levels of pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), CD32 and CD68 in MCAO mice. Triad3A and necroptosis were triggered in mouse microglia cells treated with oxygen and glucose deprivation (OGD), and in TNFα-incubated mouse hippocampal neuronal cells treated with Z-VAD-fmk, known as a pan-caspase inhibitor. Moreover, Triad3A knockdown accelerated cell death in microglial cells and neurons under these stresses. Furthermore, pre-treatment with necroptosis inhibitor markedly inhibited the cell death promoted by Triad3A silence in brain of mice with MCAO operation, demonstrating that Triad3A could regulate necroptosis to meditate the progression of cerebral I/R injury. Collectively, these finding illustrated that Triad3A could be served as a potential target for stroke therapy.


Assuntos
Encéfalo/enzimologia , Infarto da Artéria Cerebral Média/enzimologia , Microglia/enzimologia , Necroptose , Neurônios/enzimologia , Traumatismo por Reperfusão/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Encéfalo/patologia , Linhagem Celular , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/patologia , Neurônios/patologia , Proteínas Quinases/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-308858

RESUMO

<p><b>OBJECTIVE</b>To investigate the changes of clinical and EEG features in children with febrile seizures which are prone to epilepsy four years after antiepileptic drugs valproate and/or topiramate treatment.</p><p><b>METHODS</b>One hundred and thirty-two children with febrile seizures between 2004 and 2005 and who had the indications of antiepileptic drugs treatment were administered with oral valproate and/or topiramate treatment. The children were followed up for four years. Routine blood tests, liver and renal function tests were performed twice a year. Sleeping activation EEG examination was performed once a year.</p><p><b>RESULTS</b>During the follow-up of 1 to 10 years, 108 (98.2%) out of 110 children with valproate monotherapy were seizure-free. In the 110 cases, 95 were in the drug withdrawl and 10 were in the drug reduction. All of 13 cases receiving topiramate monotherapy were seizure-free and were in the drug withdrawl. None of the patients showed abnormalities in routine blood tests, liver and renal functions tests. Sleeping activation EEG showed normal in 102 cases, focal discharges in 8 cases, bilateral synchronized spikes in 4 cases and 3Hz spikes and polyspikes in 2 cases.</p><p><b>CONCLUSIONS</b>Early use of antiepileptic drugs valproate or topiramate is effective and safe in children with febrile seizures which are prone to epilepsy. The majority of the children have a normal sleeping activation EEG after antiepileptic drug therapy.</p>


Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anticonvulsivantes , Usos Terapêuticos , Eletroencefalografia , Convulsões Febris , Tratamento Farmacológico , Sono , Fisiologia
3.
Chinese Journal of Pediatrics ; (12): 648-654, 2011.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-276977

RESUMO

<p><b>OBJECTIVE</b>To study the characteristics of amplitude integrated electroencephalography (aEEG) in preterm infants and changes of maturation with gestational age.</p><p><b>METHODS</b>aEEG monitoring was done within 3 days of age with domestically produced digital aEEG set (CFM3000). Duration of each recording was at least 4 hours. The continuity, sleep-wake cycle, voltage and bandwidth of all aEEG tracing were analyzed.</p><p><b>RESULTS</b>The percent of continuity background increased from 30% of 28 weeks to 85.7% of 36 weeks (χ(2) = 28.2, P = 0.026); the percent of mature sleep-wake cycle increased from 10% of 28 weeks to 100% of 36 weeks (χ(2) = 192.4, P < 0.01). Low bound voltage increased with gestational age, from (6.8 ± 1.7) µV (28 w) to 9.7 - 10.1 µV (35 - 36 w) (F = 11.4, P < 0.01). Bandwidth of the narrow band decreases gradually with gestational age, from 1.45 cm (28 w) to (0.86 ± 0.24) cm (36 w) (F = 8.731, P < 0.01). The correlation coefficient for continuity, sleep-wake cycle, low bound voltage and bandwidth of narrow band, and total scores were 0.32, 0.81, 0.38, 0.55 and 0.78 respectively (P < 0.05).</p><p><b>CONCLUSION</b>The older the gestational age of infants at birth, the more mature the aEEG pattern, manifested as increased continuity and sleep-wake cycle, the higher low bound voltage and more narrowed bandwidth with increased gestational age.</p>


Assuntos
Feminino , Humanos , Recém-Nascido , Masculino , Fatores Etários , Eletroencefalografia , Recém-Nascido Prematuro , Fisiologia
4.
Chinese Journal of Pediatrics ; (12): 18-21, 2008.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-249467

RESUMO

<p><b>OBJECTIVE</b>Neonatal lupus erythematosus (NLE) is an uncommon autoimmune disease passively transmitted from the mother in which there is transplacental passage of maternal antibodies. It is often misdiagnosed as intrauterine infection or sepsis. The main purpose of this retrospective study was to improve the understanding of pathogenesis and clinical manifestations of NLE.</p><p><b>METHODS</b>Clinical manifestations, results of the tests for antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB and anti-dsDNA antibodies in both infants with NLE (8 cases) and their mothers and head ultrasound and CT scans of the infants were analyzed. Follow-up was performed until one and ahalf years of age or all the abnormalities had been resolved.</p><p><b>RESULTS</b>Totally 8 cases (3 males and 5 females) matched the criteria for diagnosis of NLE from September 2003 to February 2006, among whom 4 were small for gestational age and one was born prematurely. Mean gestational age was 38.1 +/- 1.9 weeks, mean birth weight 2 605 +/- 420 grams, mean admission age 22.4 +/- 27.7 days (2 hours-72 days) and mean age of onset 9.4 +/- 12.1 days (0 - 28 days). The common clinical manifestations included cutaneous lupus lesions (8 infants), neural system abnormalities (2 infants) and congenital heart block (2 infants). The skin of the infants exhibited annular, erythematous or desquamative lesions. They all disappeared before 6 months of age. One patient presented with grade III atrioventricular block and was delivered by cesarean section because of "fetal distress". He did not recover at one and a half years follow-up. One infant was hypotonic with delayed neuro-motor development initially and during follow-up with both abnormal neonatal behavioral neurological assessment (NBNA) and image findings. CT showed generalized low density involving periventricular area and deep white matter at one week of age. At the age of one and a half years, he presented with normal mental development index determined by CDCC infant intelligence mensuration. Other abnormal clinical findings included hepatosplenomegaly, anemia, thrombocytopenia, cholestasis and elevated liver enzymes, which were all resolved before 6 months of age. Only 3 mothers of the NLE infants were diagnosed as lupus erythematosus before parturition and only one received partial therapy. At least anti-Ro/SSA antibody or anti-La/SSB antibody or ANA was found in the affected patients. Seven cases had circulating anti-Ro and/or anti-La antibodies in the mothers and in the newborns, while ANA was positive in 7 newborns and in all mothers. All the clinical symptoms except congenital heart block disappeared before 18 months of age. No special intervention was applied.</p><p><b>CONCLUSION</b>Serum auto-antibodies should be investigated to rule out NLE when there is congenital heart block or rashes or thrombocytopenia presented in a neonate, despite there is no maternal history. Central nervous system abnormalities in NLE are likely to be transient and whether it will cause long term sequelae is uncertain.</p>


Assuntos
Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Autoimunes , Patologia , Doenças do Recém-Nascido , Diagnóstico , Lúpus Eritematoso Cutâneo , Diagnóstico , Patologia , Estudos Retrospectivos
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