-
[show abstract]
[hide abstract]
ABSTRACT: Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE.
Journal of Molecular Neuroscience 05/2013; · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An acute viral infection may lead to death, as seen in the recent novel 2009 influenza A (H1N1) virus pandemic that rapidly spread worldwide. Hemophagocytic lymphohistiocytosis (HLH) is a systemic disorder with high mortality rates and can be triggered by various etiological agents, including viral infections. H1N1-associated HLH is a very rare condition that may cause extremely severe complications leading to multiple organ failure (MOF) and death. We report an unusual case of a rapidly progressive and fatal H1N1 infection that was complicated with HLH and MOF in a previously healthy 8-year-old Asian female who initially presented with fever and abdominal pain. To enable early recognition and proper treatment, physicians should be aware of the possibility of this fatal complication, which may present with unusual initial symptoms.
Pediatrics & Neonatology 04/2013; · 0.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiovascular diseases in children comprise a large public health problem. The major goals of paediatric cardiologists and paediatric cardiovascular researchers are to identify the cause(s) of these diseases to improve treatment and preventive protocols. Recent studies show the involvement of microRNAs (miRs) in different aspects of heart development, function, and disease. Therefore, miR-based research in paediatric cardiovascular disorders is crucial for a better understanding of the underlying pathogenesis of the disease, and unravelling novel, efficient, preventive, and therapeutic means. The ultimate goal of such research is to secure normal cardiac development and hence decrease disabilities, improve clinical outcomes, and decrease the morbidity and mortality among children. This review focuses on the role of miRs in different paediatric cardiovascular conditions in an effort to encourage miR-based research in paediatric cardiovascular disorders.
Cardiology in the Young 02/2013; · 0.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mesial temporal lobe epilepsy (MTLE) is a particularly devastating form of human epilepsy with significant incidence of medical intractability. MicroRNAs (miRs) are small, noncoding RNAs that regulate the posttranscriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of MTLE development. To study the dynamic expression patterns of brain-specific miR-124 and miR-134 and inflammation-related miR-132 and miR-21, we performed qPCR on the hippocampi of immature rats at 25 days of age. Expressions were monitored in the three stages of MTEL and in the control hippocampal tissues corresponding to the same timeframes. A similar expression method was applied to hippocampi obtained from children with MTLE and normal controls. The expression patterns of miR-124 and miR-134 nearly showed the same dynamics in the three stages of MTLE development. On the other hand, miR-132 and miR-21 showed significant upregulation in acute and chronic stages, while in the latent stage, miR-132 was upregulated and miR-21 was downregulated. The four miRs were upregulated in hippocampal tissues obtained from children with MTLE. The significant upregulation of miR-124 and miR-134 in the seizure-related stages and children suggested that both can be potential targets for anticonvulsant drugs in the epileptic developing brains, while the different expression patterns of miR-132 and miR-21 may suggest different functions in MTLE pathogenesis.
Journal of Molecular Neuroscience 01/2013; · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The pandemic of the childhood obesity represent a major public health problem all over the world. This leads to detection of many health conditions that were previously considered an adulthood diseases. The rise in the prevalence of the obesity and overweight among children means that the world will face an explosion in the prevalence of the metabolic syndrome (MS), which increases the risk of atherosclerotic disease and death in adulthood. The atherosclerotic process has proved to develop silently for decades during childhood and adolescence before the cardiovascular complications such as myocardial infarction and stroke occur. This means that obese children especially with MS could have heart attacks and suffer from heart disease in an age when they should be very healthy, but most of these data either derived from autopsy findings or studies that confirmed the presence of peripheral atherosclerosis. Very early detection of coronary atherosclerosis in obese children with metabolic syndrome through a non invasive method will be of great importance, allowing for early therapeutic intervention. The discovery of microRNAs (miRNAs) is considered a major scientific breakthrough in the last years; recent studies have suggested a potentially important role of miRNAs in the control of diversity aspects of cardiac functions in health and disease including coronary atherosclerosis. Moreover, circulating miRNAs profiles recently used as a non-invasive biomarker for diagnosis of multiple cardiovascular diseases. The identification of distinct circulating miRNA profiles may impact the development of specific miRNAs as biomarkers in pediatric cardiovascular diseases. Therefore, we postulate that some of these circulating miRNAs may be a potential biomarker for early non-invasive diagnosis of coronary atherosclerosis in very early asymptomatic stage in obese children with metabolic syndrome, giving an excellent chance to fight against the first killer in the adult population in childhood period.
Medical Hypotheses 10/2012; · 1.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Escherichia coli endotoxin LPS regulates blood-brain barrier permeability by disrupting the tight junction (TJ) complex between brain endothelial cells. This study used Bend.3 cells to examine the signaling networks involved in the hyperpermeability of the brain endothelial barrier caused by LPS. The LPS-induced alterations in the brain endothelial barrier were associated with PKC (a, β, ζ) and RhoA, but were independent of PI3K and the tyrosine kinase pathway. Inhibition of PKC (a, β, ζ) and RhoA activity using shRNA and dominant negative mutants diminished the effects of LPS on the brain's endothelial TJs. The interactions between the PKC and Rho pathways were therefore examined. PKC-a and PKC-ζ, but not PKC-β interacted with RhoA in Bend.3 cells stimulated by LPS. PKC-a acted as the upstream molecule for Rho and PKC-ζ acted as the downstream target for Rho. Comparing the effect of double inhibition of "Rho and PKC" and single inhibition of "Rho" or "PKC" confirmed that this interaction is critical for LPS-induced brain endothelial cell hyperpermeability. Collectively these data are the first to suggest that LPS affects the brain's endothelial TJ barrier via PKC (a, β, ζ)- and RhoA, independent of the PI3K and tyrosine kinase pathways. In addition, PKC-a and PKC-ζ, respectively, act as the upstream and downstream regulator for RhoA in the process.
Biochemical and Biophysical Research Communications 07/2012; 425(2):182-8. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although there have been tremendous advances in the diagnosis and treatment of pediatric brain diseases in the last few decades, the causes and pathogenesis of these diseases remain to be elucidated. Pediatric central nervous system (CNS) diseases create both short- and long-term impairments and disabilities and are therefore one of the leading causes for emotional, financial, and social burden to patients, their families, and their social network. The significant pediatric morbidity and mortality rates caused by CNS diseases call for equally significant efforts toward a better understanding of the etiology and nature of these disorders. Recent studies show the involvement of microRNAs (miRNAs) in various aspects of central nervous system development and neuropsychiatric diseases. This review focuses on the role of miRNAs in different pediatric neurological conditions. We emphasize the importance of microRNA-based research in combating pediatric neurological disorders. We believe this approach will result in novel therapies to secure normal development and prevent disabilities in the pediatric population.
Neuromolecular medicine 07/2012; · 5.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thrombocytopenia with absent radii is a rare congenital defect with hypomegakaryocytic thrombocytopenia and bilateral radial aplasia that may have additional anomalies. We report the case of a girl baby with thrombocytopenia and absent radii syndrome and bilateral congenital cataract. This anomaly has not been previously reported in the children of a non- consanguineous marriage.
This case report describes a two-day-old girl baby of Arab origin with thrombocytopenia and absent radii syndrome and bilateral congenital cataract.
This report describes a finding of bilateral congenital cataract associated with thrombocytopenia and absent radii syndrome that has been reported only once before in the literature. This case report highlights a new ocular manifestation in one of the bone marrow failure syndromes.
Journal of Medical Case Reports 06/2012; 6(1):168.
-
[show abstract]
[hide abstract]
ABSTRACT: Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)-1β as a proinflammatory cytokine and microRNA (miR)-146a as a posttranscriptional inflammation-associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE.
To study the expression of IL-1β and miR-146a, we performed a reverse transcription polymerase chain reaction, Western blot, and real-time quantitative PCR on the hippocampi of immature rats at 11 days of age. Expression was monitored in the acute, latent, and chronic stages of disease (2 h and 3 and 8 weeks after induction of lithium-pilocarpine status epilepticus, respectively), and in control hippocampal tissues corresponding to the same timeframes. Similar expression methods were applied to hippocampi obtained from children with MTLE and normal controls.
The expression of IL-1β and miR-146a in both children and immature rats with MTLE differs according to the stage of MTLE development. Both IL-1β and miR-146a are significantly up-regulated, but in opposite ways: IL-1β expression is highest in the acute stage, when expression of miR-146a is at its lowest level; miR-146a expression is highest in the latent stage, when IL-1β expression is at its lowest level. Both IL-1β and miR-146a are up-regulated in the chronic stage, but not as much as in the other stages.
Our study is the first to focus on the expression of miR-146a in the immature rat model of lithium-pilocarpine MTLE and in children with MTLE. We have detected that the expression of proinflammatory cytokine IL-1β and posttranscriptional inflammation-associated miR-146a is variable depending on the disease stage. Furthermore, both IL-1β and miR-146a are up-regulated in immature rats and children with MTLE. Our findings elucidate the role of inflammation in the pathogenesis of MTLE in the immature rat model and children. Therefore, modulation of the IL-1β-miR-146a axis may be a novel therapeutic target in the treatment of MTLE.
Epilepsia 06/2012; 53(7):1215-24. · 3.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate the signaling mechanisms surrounding changes in tight junction (TJ) and the permeability of human intestinal epithelial cell induced by tumor necrosis factor-alpha (TNF-α).
To confirm that TNF-α induces epithelial barrier hyperpermeability by disrupting tight junction, Caco-2 cells were exposed to TNF-α, and changes in epithelial permeability (via TER assay), F-actin dynamics (via Rhodamine-phalloidin staining) and tight junction protein expression (via western blot) were monitored. Moreover, to ensure that NF-κB participated in the regulatory mechanisms, Caco-2 cells were transfected with DNMu-IκBα or control plasmids, the above experiments were repeated and the activation effect of TNF-α on NF-κB was detected by luciferase reporter assays. Lastly, we took dominant negative plasmid and knockdown approaches to investigate the potential importance of the NF-κB/myosin light chain kinase (MLCK)/myosin light chain phosphorylation (pMLC) pathways in TNF-a-mediated damage.
TNF-α could cause NF-κB activation, F-actin rearrangement, tight junction disruption and barrier dysfunction. These effects were alleviated by inhibiting NF-κB. TNF-α induced increase of MLCK transcription and MLC phosphorylation act later than NF-κB activation, which could be suppressed both by inactivating and deleting NF-κB.
TNF-α induces intestinal epithelial cell hyperpermeability by disrupting TJs, in part through MLCK upregulation, in which NF-κB is the positive upstream regulator for MLCK.
Cytokine 05/2012; 59(2):264-72. · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary hypothyroidism in the juvenile population generally leads to retardation of linear growth and delay or even arrest of puberty. However, in rare conditions, children with long-standing hypothyroidism present with signs of Van Wyk-Grumbach's syndrome (VWGS) which include juvenile hypothyroidism, delayed bone age, and pseudoprecocious puberty. We report a rare case of prepubertal male child from Asian origin, presented with long-standing untreated hypothyroidism complicated with VWGS and other complications including obesity, short stature, hepatomegaly, asymptomatic mild pericardial effusion, and pituitary hyperplasia.
Case reports in pediatrics. 01/2012; 2012:352751.
-
[show abstract]
[hide abstract]
ABSTRACT: Hydrocephalus is a common complication of tuberculous meningitis (TBM) in children. The role of ventriculoperitoneal shunt (VPS) placement in grade IV patients is controversial. The aim of this study is to investigate the clinical value of VPS placement for patients with grade IV TBM with hydrocephalus (TBMH).
This study was carried out on children with grade IV TBMH from January 2006 to January 2011 in Xiangya Hospital, China. All patients were given VPS placement combined with medicine treatment. External ventricular drainage (EVD) was performed only in the presence of severe biochemical derangements or brainstem dysfunction requiring correction before shunt surgery. Outcomes were divided into normal, mild sequelae, severe sequelae, death, or vegetable status.
A total of 19 children with grade IV TBMH were recruited into the study. The average follow-up period was 29 months. Three of the 19 patients expired, four patients had a full recovery, eight had slight sequelae, and four had severe sequelae. Six complications related to the shunt surgery were seen among the patients.
This study demonstrates that direct ventriculoperitoneal shunt surgery could improve the outcome of grade IV TBMH. The response to EVD is not a reliable indication for selecting patients who would benefit from shunt surgery.
Child s Nervous System 09/2011; 28(2):209-15. · 1.54 Impact Factor
