Current Approaches to the Treatment of Head Injury in Children

Head trauma is one of the most challenging fields of traumatology and demands immediate attention and intervention by first-line clinicians. Symptoms can vary from victim to victim and according to the victim's age, leading to difficulties in making timely and accurate decisions at the point of care. In children, falls, accidents while playing, sports injuries, and abuse are the major causes of head trauma. Traffic accidents are the main cause of disability and death in adolescents and adults. Injury sites include facial bones, muscles, ligaments, vessels, joints, nerves, and focal or whole-brain injuries. Of particular importance are cranial and intracranial injuries. A closed injury occurs when the head suddenly and violently hits an object but the object does not break through the skull. A penetrating injury occurs when an object pierces the skull and affects the brain tissue. Early diagnosis and proper management are crucial to treat patients with potentially life-threatening head and neck trauma. In this review, we discuss the different cases of traumatic brain injury and summarize the current therapies and neuroprotective strategies as well as the related outcomes for children with traumatic brain injury

Current Proceedings of Childhood Stroke

Stroke is a sudden onset neurological deficit due to a cerebrovascular event. In children, the recognition of stroke is often delayed due to the low incidence of stroke and the lack of specific assessment measures to this entity. The causes of pediatric stroke are significantly different from that of adult stroke. The lack of safety and efficiency data in the treatment is the challenge while facing children with stroke. Nearly half of survivors of pediatric stroke may have neurologic deficits affecting functional status and quality of life. They may cause a substantial burden on health care resources. Hence, an accurate history, including onset and duration of symptoms, risk factors, and a complete investigation, including hematologic, neuroimaging, and metabolic studies is the key to make a corrective diagnosis. A prompt and optimal treatment without delay may minimize the damage to the brain

Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2-Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors.

BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells. CONCLUSIONS: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance

Kefir peptides attenuate atherosclerotic vascular calcification and osteoporosis in atherogenic diet-fed ApoE−/− knockout mice

Aims: Vascular calcification (VC) and osteoporosis were previously considered two distinct diseases. However, current understanding indicates that they share common pathogenetic mechanisms. The available medicines for treating VC and osteoporosis are limited. We previously demonstrated that kefir peptides (KPs) alleviated atherosclerosis in high-fat diet (HFD)-induced apolipoprotein E knockout (ApoE−/−) mice. The present study further addressed the preventive effects of KPs on VC and osteoporosis in ApoE−/− mice fed a high-cholesterol atherogenic diet (AD).Main methods: Seven-week-old ApoE−/− and wild-type C57BL/6 mice were randomly divided into five groups (n = 6). The development of VC and osteoporosis was evaluated after AD feeding for 13 weeks in KP-treated ApoE−/− mice and compared to C57BL/6 and ApoE−/− mice fed a standard chow diet (CD).Key findings: The results indicated that KP-treated ApoE−/− mice exhibited lower serum total cholesterol, oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) levels, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine kinase (CK) activities, which suggested that KPs prevented hyperlipidemia and possible damages to the liver and muscle in ApoE−/− mice. KPs reduced serum tumor necrosis factor-α (TNF-α) and the local expression of TNF-α, IL-1β, and macrophage-specific CD68 markers in aortic tissues, which suggested that KPs inhibited inflammatory responses in AD-fed ApoE−/− mice. KPs reduced the deposition of lipid, collagen, and calcium minerals in the aortic roots of AD-fed ApoE−/− mice, which suggested that KPs inhibited the calcific progression of atherosclerotic plaques. KPs exerted osteoprotective effects in AD-fed ApoE−/− mice, which was evidenced by lower levels of the bone resorption marker CTX-1 and higher levels of the bone formation marker P1NP. KPs improved cortical bone mineral density and bone volume and reduced trabecular bone loss in femurs.Significance: The present data suggested that KPs attenuated VC and osteoporosis by reducing oxidative stress and inflammatory responses in AD-fed ApoE−/− mice. Our findings contribute to the application of KPs as preventive medicines for the treatment of hyperlipidemia-induced vascular and bone degeneration

Prognostic values of a combination of intervals between respiratory illness and onset of neurological symptoms and elevated serum IgM titers in Mycoplasma pneumoniae encephalopathy

Background/PurposeTo retrospectively analyze the clinical manifestations of Mycoplasma pneumoniae (M. pneumoniae)-associated encephalopathy in pediatric patients.MethodsPediatric patients with positive serum anti-M. pneumoniae immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms, laboratory data, neuroimaging findings, and electrophysiological data were reviewed.ResultsOf 1000 patients identified, 11 (1.1%; male:female ratio = 7:4) had encephalopathy and were admitted to the pediatric intensive care unit. Clinical presentation included fever, symptoms of respiratory illness, and gastrointestinal upset. Neurological symptoms included altered consciousness, seizures, coma, focal neurological signs, and personality change. Neuroimaging and electroencephalographic findings were non-specific. Specimens of cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were negative. Higher M. pneumoniae IgM titers and longer intervals between respiratory and CNS manifestations were associated with worse outcomes.ConclusionClinical manifestations of M. pneumoniae-associated encephalopathy were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between respiratory and CNS manifestations might be possibly related to the prognosis of patients with M. pneumoniae-associated encephalopathy

Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+ T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+ T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+ T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper

Effective Radiotherapy Cured Cauda Equina Syndrome Caused by Remitted Intracranial Germinoma Depositing

Cauda equina syndrome (CES) in children is very rare and can permanently disable. A remitted intracranial germinoma depositing on the spinal cord, leading to CES, has never been reported. We discuss the case of a 10-year-old girl who presented with sudden ataxia, low back pain, sensory deficits of the left lower extremity, and difficulty urinating and defecating 7 months after totally remitted intracranial germinoma postintracranial surgery and cranial irradiation. Magnetic resonance imaging (MRI) of the brain and spine showed multiple intradural extramedullary homogeneous masses from the cervical to lumbar levels, compressing the conus medullaris and cauda equina. After emergent craniospinal irradiation, the patient's neurologic symptoms dramatically subsided. A remitted intracranial germinoma depositing on her spinal cord could be the cause of CES. Early identification and a proper craniospinal irradiation may halt the progression of symptoms

The impact of the use of antiepileptic drugs on the growth of children

BACKGROUND: This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. METHODS: Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. RESULTS: One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p < 0.005) compared with the control group. The underlying mechanism may have been due to the direct effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. CONCLUSIONS: These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA

Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome