多药耐药相关蛋白与难治性癫(癎)发病关系的研究进展

难治性癫(癎)的耐药机制尚不清楚.近年来研究认为与多药耐药相关蛋白关系密切,其耐药机制可能与多药耐药相关蛋白在癫(癎)脑组织中高表达有关,通过将药物从细胞内泵到细胞外,从而降低脑内的药物浓度而使之产生耐药性.多药耐药相关蛋白在调节癫(癎)患儿细胞内外抗癫(癎)药物浓度时发挥重要作用.其特异性抑制剂可能提高抗癫(癎)药在难治性癫(癎)中的作用,因此,对多药耐药相关蛋白的深入研究可能会为今后临床治疗难治性癫(癎)提供新方法及为新的抗癫(癎)药物的研究提供新的方向.     

难治性癫(癎)与多药转运体关系的研究进展

儿童癫癎是儿科神经系统常见的一种发作性疾病,其中20%～30%为难治性癫癎(IE).儿童IE的发病机制尚不明确,国内外研究认为可能与不同作用机制的多种抗癫癎药耐药有关,与多药耐药基因表达异常有关.目前研究多药转运体抗癫癎药物耐药机制最多的有p-糖蛋白、多药耐药相关蛋白,二者是存在于细胞膜上的蛋白质趟家族,属于ATP依赖的膜转运蛋白.研究显示IE患者颞叶脑组织及慢性癫癎动物模型中p-糖蛋白、多药耐药相关蛋白等多药转运体过度表达,它们通过利用分解ATP所释放的能量,以主动转运的方式将大量抗癫癎药物转运到大脑毛细血管内皮细胞之外,降低治疗药物在细胞内的水平,从而产生耐药.现就多药转运体的结构、分布、功能及其与癫癎耐药的关系作一综述.     

拉莫三嗪对癫癎幼鼠海马中多药耐药基因表达的影响

癫癎是一种常见的神经系统疾病,约有25%的癫癎患者对大部分抗癫癎药物耐药,从而发展为难治性癫癎[1].越来越多的学者认为难治性癫癎的耐药机制可能与多种药物运输蛋白的过最表达、抗癫癎药物不能有效地进入脑细胞有关,其中多药耐药基因(multidrug resistance gene,MDR)及其表达产物P-gp备受关注.     

难治性癫(癎)患儿多药耐药基因的表达及意义

目的 研究难治性癫(癎)(RE)患儿多药耐药基因(MDR1)的表达及其临床意义.方法 提取难治性癫(癎)患儿(n=30)、非难治性癫(癎)患儿(n=30)和正常健康儿童(n=30)外周血标本,用荧光定量PCR方法分析比较MDR1 mRNA在各组的表达.同时观察MDR1 mRNA水平与癫(癎)发作频率和应用抗癫(癎)药物(AEDs)的种类与数量关系.结果 MDR1 mRNA在难治性癫(癎)组表达明显高于非难治性癫(癎)组及正常对照组(P均<0.01);在发作次数频繁患儿明显高于发作次数较少患儿(P<0.01);在使用4种AEDs患儿明显高于使用2种及3种AEDs息儿(P<0.05).结论 血中高表达的MDR1参与了难治性癫(癎)的耐药机制,可作为判断难治性癫(癎)的客观指标.     

难治性癫(癎)耐药的分子生物学机制

癫(癎)是儿科常见病、多发病.虽然大多数癫(癎)患儿经过目前正规临床药物治疗后可以获得满意的控制,但仍约有20%～30%发作得不到有效控制而成为难治性癫(癎).其治疗困难的原因一方面与其发病机制复杂有关,另一方面则是由于多药耐受,即对不同化学结构、不同作用方式的临床常用的多种抗癫(癎)药物(anti-epileptic drugs,AED)产生耐药性.癫(癎)多药耐受的原因有:病变或癫(癎)发作造成药物作用靶点的改变,使AED的敏感性减低;多药耐受基因及其编码药物转运体蛋白如P糖蛋白、多药耐药相关蛋白、穹隆体主蛋白等多种蛋白过度表达,使AED通过血脑屏障时被主动泵出增加,局部的AED达不到有效浓度;谷胱甘肽转移酶活性增高加快了脑内药物的降解速度,从而降低了脑组织局部药物浓度等都参与了癫(癎)多药耐受的发生.     

儿童难治性癫(癎)外周血P糖蛋白的表达及药物干预

目的 测定儿童难治性癫(癎)及初诊癫(癎)患儿外周血白细胞多药耐药基因产物P糖蛋白(P-gp),建立儿童难治性癫(癎)耐药性客观指标及预测儿童难治性癫(癎)客观指标;同时观察氟桂利嗪的疗效.方法 应用流式细胞仪检测41例难治性癫(癎)儿童及45例初诊癫(癎)儿童外周血多药耐药基因产物P-gp的表达,44例健康儿为对照组.难治性癫(癎)组患儿加用氟桂利嗪(弗瑞林)2.5～5 mg,qn口服治疗,对其疗效进行临床验证.结果 难治性癫(癎)组P-gp表达阳性23例(56.1%),初诊癫(癎)组P-gP表达阳性10例(22.2%),对照组P-gp表达阳性3例(6.8%),三组比较差异有统计学意义(X2=26.77,P(0.01).难治性癫(癎)组与对照组比较X2=24.27,P<0.01;难治性癫(癎)组与初诊癫痫组比较X2=10.41,P<0.01;初诊癫痫组与对照组比较X2=4.23,P<0.05.难治性癫痫组P-gp表达阳性23例中17例(73.9%)无效,6例(26.1%)有效,P-gP表达阴性18例中3例(16.7%)无效,15例(83.3%)有效,两者比较差异有统计学意义(X2=10.10,P<0.01).初诊癫痫组P-gp表达阳性10例中7例(70.0%)转为难治性癫(癎),P-gp表达阴性35例中3例(18.6%)转为难治性癫(癎).两者比较差异有统计学意义(X2=16.98,P<0.01).难治性癫(癎)组抗癫(癎)药物治疗无效者20例加用氟桂利嗪治疗3个月,P-gP表达阳性17例中有效11例(64.7%),11例有效者复查P-gP有6例(54.5%)转为阴性;无效6例(35.3%),复查P-gP表达仍阳性.P-gP表达阴性3例中1例有效,2例无效,复查P-gp表达阴性.结论 外周血多药耐药基因产物P-gP在儿童难治性癫(癎)中表达增强,可作为儿童难治性癫(癎)耐药性的客观指标;P-gP表达阳性的初诊癫(癎)患儿多转为难治性癫(癎),P-gP可作为预测儿童难治性癫(癎)的客观指标;氟桂利嗪有一定抗癫(癎)及逆转P-gP的表达作用.     

多药耐药基因C3435T多态性与儿童难治性癫癎耐药的Meta分析

目的探讨多药耐药基因(MDR1)C3435T多态性与儿童难治性癫癎耐药的关系。方法利用计算机在万方数据库、中国知网数据库、维普数据库和PubMed数据库中检索MDR1 C3435T多态性与儿童难治性癫癎耐药发生的文献,并应用RevMan 5.0软件对符合入选标准的文献进行异质性检验和效应值合并,同时进行敏感性分析和偏倚评估。结果纳入符合条件的相关文献5篇,共计难治性癫癎药物耐药组367例,药物敏感组488例。MDR1 CT、TT、CT+TT与儿童难治性癫癎耐药的合并OR值(95%CI)分别为0.89(0.65～1.23)、0.94(0.56～1.57)、0.92(0.64～1.32),Z=0.69、0.25、0.46,P=0.49、0.80、0.64。各研究的敏感性分析较稳定且无发表偏倚。结论 MDR1 C3435T多态性与儿童难治性癫癎耐药的发生无关。     

非传统抗癫(癎)药物防治小儿癫(癎)的研究进展

癫(癎)是儿童神经系统的常见病和多发病,严重危害儿童的身心健康.目前,抗癫(癎)药物仍然是治疗儿童癫(癎)的主要手段,传统的抗癫癎药物疗效确切但不良反应较大,患者不易耐受,并且部分患者出现耐药.非传统抗癫(癎)药物疗法可能在药物难治性癫(癎)以及不能耐受抗癫(癎)药物毒性的患儿中发挥一定的作用.     

非传统抗癫(癎)药物防治小儿癫(癎)的研究进展

癫(癎)是儿童神经系统的常见病和多发病,严重危害儿童的身心健康.目前,抗癫(癎)药物仍然是治疗儿童癫(癎)的主要手段,传统的抗癫癎药物疗效确切但不良反应较大,患者不易耐受,并且部分患者出现耐药.非传统抗癫(癎)药物疗法可能在药物难治性癫(癎)以及不能耐受抗癫(癎)药物毒性的患儿中发挥一定的作用.     

难治性癫(癎)多药耐药机制的研究进展

多药物抵抗是药物治疗难治性癫(癎)的主要障碍.有研究表明,多药物转运子P糖蛋白的表达增加和活性增强,阻止抗癫(癎)药物进入大脑是多药物抵抗的主要机制.另外有研究发现P糖蛋白的表达和活性与谷氨酸盐/NMDA受体/COX-2信号途径有关,这可能成为新的解决癫(癎)多药物抵抗的靶点.     

Fetal origins of cardiovascular disease

Several epidemiologic studies have shown that intrauterine growth retardation is a risk factor for the development of cardiovascular disease in later life. In this review, we discuss these epidemiologic studies and animal models that have been developed to investigate the pathophysiology of this phenomenon. We discuss data suggesting that intrauterine growth retardation leads to fetal exposure to maternal glucocorticoids. In addition, we present other data showing that fetal exposure of glucocorticoids during specific times of fetal development results in focal and segmental glomerulosclerosis, a reduced number of nephrons, hypertension, and diabetes. These studies suggest that at critical times during fetal development fetal injury programs the development of cardiovascular disease and diabetes in later life.     

Observation of parent-child interaction with two- to three-year-olds

A method of home observations of mother-child interaction is described. Its development is outlined in terms of the relevant conceptual and methodological issues, and the concomitant tactical decisions involved in development are discussed. The scheme focuses on parental responsivity, affect, social communication and social control, and a novel combination of time-interval and event-sequential recording is used to discriminate parental functioning in these areas. The measures have been shown to have a satisfactorily high level of reliability, and preliminary analysis indicates construct validity.     

The impact of development of the gut on infant nutrition

We have described the developmental pattern of the GI tract, constituent tissues of which do not develop simultaneously, either functionally or morphologically. Dietary modifications to suit the stage of development have been described, and possible changes resulting from these modifications are also discussed. It is important to note that the newborn period is a time in which rapid development is taking place while the GI system is still not fully mature, hence the macro- and micronutrients given during this period should be adjusted both quantitatively and qualitatively to suit the needs of the infant, particularly so if he is premature or compromised.     

重庆地区男童包皮发育的流行病学调查

目的调查男童包皮发育情况，分析男童包皮疾病诊治现状。方法将10421名0～18岁儿童按年龄分为6组，观察各组包皮发育情况，调查并记录其诊治现状。结果新生儿包茎发生率为99．7％，青春期包茎发生率为6．81％，包皮完全可上翻的比例随年龄增长而逐渐增加。结论包茎在儿童时期很普遍，是儿童包皮发育的生理表现，大多数儿童的包皮至青春期可完全上翻。目前存在包茎过度诊断及过度治疗的现象。     

Annotation: Development of facial expression recognition from childhood to adolescence: behavioural and neurological perspectives

BACKGROUND: Intact emotion processing is critical for normal emotional development. Recent advances in neuroimaging have facilitated the examination of brain development, and have allowed for the exploration of the relationships between the development of emotion processing abilities, and that of associated neural systems. METHODS: A literature review was performed of published studies examining the development of emotion expression recognition in normal children and psychiatric populations, and of the development of neural systems important for emotion processing. RESULTS: Few studies have explored the development of emotion expression recognition throughout childhood and adolescence. Behavioural studies suggest continued development throughout childhood and adolescence (reflected by accuracy scores and speed of processing), which varies according to the category of emotion displayed. Factors such as sex, socio-economic status, and verbal ability may also affect this development. Functional neuroimaging studies in adults highlight the role of the amygdala in emotion processing. Results of the few neuroimaging studies in children have focused on the role of the amygdala in the recognition of fearful expressions. Although results are inconsistent, they provide evidence throughout childhood and adolescence for the continued development of and sex differences in amygdalar function in response to fearful expressions. Studies exploring emotion expression recognition in psychiatric populations of children and adolescents suggest deficits that are specific to the type of disorder and to the emotion displayed. CONCLUSIONS: Results from behavioural and neuroimaging studies indicate continued development of emotion expression recognition and neural regions important for this process throughout childhood and adolescence. Methodological inconsistencies and disparate findings make any conclusion difficult, however. Further studies are required examining the relationship between the development of emotion expression recognition and that of underlying neural systems, in particular subcortical and prefrontal cortical structures. These will inform understanding of the neural bases of normal and abnormal emotional development, and aid the development of earlier interventions for children and adolescents with psychiatric disorders.     

Role of angiotensin-converting enzyme gene polymorphisms in children with sepsis and septic shock

Background: Sepsis is characterized by a systemic inflammatory response. Its development and outcome are associated with host defense, pathogenicity of the microorganism and genetic polymorphisms. Genetic polymorphisms of the immune system genes have been shown to have a close relationship with the clinical outcomes of sepsis. Angiotensin-converting enzyme (ACE) plays a major role in the host defense against invading pathogens. It is therefore likely that polymorphisms in the ACE gene may have an important effect on determining the development and the outcome of sepsis.
Methods: Ninety-eight children diagnosed as having sepsis and 287 healthy children were included in the study. Insertion/deletion polymorphisms were analyzed using reverse-hybridization assay.
Results: The carriers of I allele (D/I genotype and I/I genotype) were found to have an increased risk of developing sepsis compared to the controls.
Conclusion: DD genotype may play a positive role against the development of sepsis in healthy children.     

Current advances in prenatal imaging of congenital diaphragmatic [corrected] hernia

Congenital diaphragmatic hernia, despite advances in therapy, remains a complex condition with significant morbidity and mortality. The etiology of the disorder is still incompletely understood, though the pulmonary hypoplasia and pulmonary hypertension that develop secondarily must be overcome to improve survival. Prenatal US and fetal MRI have helped in the development of a greater understanding of this disease. Also with these modalities, measurement techniques have been developed in an attempt to provide prognosticators for the development of pulmonary hypoplasia and pulmonary hypertension. There is a broad range of approaches for performing these measurements, and variability among imaging centers is noted. Despite inconsistent approaches, these techniques have become the foundation for counseling and prenatal and postnatal therapy. It is hoped that with further research with prenatal US and fetal MRI and the development of innovative medical and surgical therapies that the morbidity and mortality of children with congenital diaphragmatic hernias can be significantly reduced.     

The role of dietary interventions in the prevention of IgE‐mediated food allergy in children

Over the last 30 years, the prevalence of food allergy has been on the rise and remains a disease that can have a significant impact on the quality of life of children and their families. There are several hypotheses that have been suggested to account for the increasing prevalence, but this review will focus on the impact that dietary factors have on food allergy development. In the past food allergy, prevalence has largely focused on allergen avoidance; however, there is increasing evidence from interventional studies that have shown that early introduction to potential food allergens may have a beneficial role in allergy prevention. This review aims to look at the evidence in support of early introduction of allergens into infant diets to prevent against the development of food allergy.