脑梗死患者胰岛素抵抗与血管内皮功能损伤机制研究

目的 通过检测脑梗死患者胰岛素抵抗水平以及血管内皮功能损伤程度,以探讨胰岛素抵抗与血管内皮损伤的相关性.方法 试验分组:脑梗死合并高血压患者30例,脑梗死合并高血压及糖尿病患者25例,无脑梗死、高血压、糖尿病的患者20例作为对照组.以胰岛素稳态(HOMA-IR)方法检测患者胰岛素抵抗水平,以ELISA方法检测患者血管内皮功能(ADMA、VE-Ca)的损伤程度.结果 (1)脑梗死组患者的HOM A-IR高于对照组(P＜0.01),脑梗死合并高血压及糖尿病组患者的HOMA-IR高于脑梗死合并高血 压组患者(P＜0.01).(2)脑梗死组患者的内皮功能损伤较对照组严重,血清ADMA、VE-Ca浓度高于对照组(P＜0.01),脑梗死合并高血压及糖尿病组患者血管内皮功能损伤程度较脑梗死合并高血压组严重,血清ADMA、VE-Ca浓度增高明显(P＜0.01).(3)胰岛素抵抗与血管内皮功能损伤存存明显的相关性,ADMA随着HOMA-IR的升高而升高,R=0.901(P＜0.01),VE-Ca亦随着HOMA-IR的升高而升高,R=0.932(P＜0.01).结论 脑梗死患者存在血管内皮功能损伤,危险因素越多,血管内皮功能损伤越严重,其机制可能通过胰岛素抵抗引起.     

盐酸小檗碱与二甲双胍对精神分裂症伴代谢综合征患者调节脂代谢的影响

目的探讨盐酸小檗碱和二甲双胍对精神分裂症合并代谢综合征患者调节脂代谢的疗效,以及与胰岛素抵抗的关系。方法将89例奥氮平单药治疗的患者随机分为合并小檗碱组(研究组,n=43)及合并二甲双胍组(对照组,n=46),疗程12周。测定两组患者治疗前后的体重、体质量指数(BMI)、空腹血糖(FPG)、空腹胰岛素(Fins)、胆固醇(TC)、甘油三酯(TG)、脂联素(APN)、瘦素(LEP)水平,并计算胰岛素抵抗指数(HOMA-IR)。应用副反应评定量表(TESS)评估药物安全性。结果两组在治疗后的体重、BMI、TC、TG、APN、LEP、HOMA-IR水平较治疗前显著改善(P均0.01)。治疗12周,两组间比较上述各指标均无显著性差异(P均0.05)。研究组HOMA-IR变化值与TC、TG、LEP变化值均呈显著正相关(P均0.05),与APN变化值呈显著负相关(P0.05)。两组药物不良反应比较差异均无统计学意义(P均0.05)。结论盐酸小檗碱能明显降低精神分裂症MS患者的体重,调节脂质代谢异常,与二甲双胍疗效相当,这可能与其改善胰岛素抵抗有关。     

急性脑梗死患者简易胰岛素抵抗指数水平的临床研究

目的观察急性脑梗死患者的甘油三酯血糖指数(简易胰岛素抵抗指数TyG)和稳态模型评估的胰岛素抵抗指数(HOMA-IR)特点,并分析两指数的相关性。方法采用放射免疫法测定46例急性脑梗死(ACI)及40例健康对照者的空腹血胰岛素、空腹血糖、TG水平,计算简易胰岛素抵抗指数(TyG)和稳态模型评估法胰岛素抵抗指数(HOMA-IR)。结果急性脑梗死组TyG和HOMA-IR均较对照组增高(P0.05);急性脑梗死组和对照组TyG和HOMA-IR具有良好的相关性(分别为r=0.34,P0.05;r=0.27,P0.05)。结论急性脑梗死患者存在胰岛素抵抗,TyG评价胰岛素抵抗是一种简单准确的方法。     

L6大鼠成肌细胞胰岛素信号传导通路中磷脂酰肌醇3激酶、蛋白激酶B和葡萄糖转运蛋白4的表达**★

背景：血管紧张素Ⅱ可损伤胰岛素信号中的下游信号分子引起胰岛素抵抗，但其机制不清。 目的：观察血管紧张素Ⅱ对L6大鼠成肌细胞胰岛素信号传导通路中磷脂酰肌醇3激酶、蛋白激酶B和葡萄糖转运蛋白4的影响。 方法：L6细胞培养及诱导分化肌管，根据干预措施不同实验分为对照组、胰岛素组、胰岛素+血管紧张素Ⅱ组及胰岛素+血管紧张素Ⅱ+H89组。采用RT-PCR检测4组磷脂酰肌醇3激酶、蛋白激酶B mRNA表达，免疫荧光检测胰岛素受体底物1、酪氨酸磷酸化胰岛素受体底物1、葡萄糖转运蛋白4表达。 结果与结论：胰岛素组、胰岛素+血管紧张素Ⅱ组及胰岛素+血管紧张素Ⅱ+H89组的磷脂酰肌醇3激酶mRNA表达均较对照组显著升高(P < 0.05)。各组间蛋白激酶B mRNA表达差异无显著性意义(P > 0.05)。相比对照组，其余3组间胰岛素受体底物1、酪氨酸磷酸化胰岛素受体底物1和葡萄糖转运蛋白4(膜蛋白)表达均升高(P < 0.05)；胰岛素+血管紧张素Ⅱ+H89组酪氨酸磷酸化胰岛素受体底物1和葡萄糖转运蛋白4表达低于胰岛素组但高于胰岛素+血管紧张素Ⅱ组(P < 0.05)。结果显示，血管紧张素Ⅱ在骨骼肌细胞中通过JAK2-PKA通路引起胰岛素下游信号传导受阻，葡萄糖转运蛋白4表达减少，葡萄糖转运障碍，进而导致胰岛素抵抗。     

阿尔茨海默病精神行为症状与代谢综合征关系研究

目的探讨阿尔茨海默病(AD)精神行为症状(BPSD)与代谢综合征(MS)的关系。方法对符合美国精神病学会(APA)《精神障碍诊断与统计手册(第4版)》(DSM-IV)AD诊断标准的102例住院患者进行研究,采用自制一般情况调查表收集人口学资料和病史资料,测量身高、体质量、腰围、血压等生理指标,早晨空腹取静脉血5ml,检测空腹血糖、总蛋白、白蛋白、球蛋白、肌酐、尿素氮、尿酸、甘油三酯、总胆固醇、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)等生化指标,按2007年颁布的《中国成人血脂异常防治指南》中MS诊断标准诊断MS,采用神经精神问卷(NPI)测评BPSD。结果 102例AD患者中,符合MS诊断标准者66例,检出率为64.71%。MS组妄想、激越、易激惹检出率高于非MS组,差异有统计学意义(P0.05或0.01)。结论 MS对AD患者BPSD有影响。对MS进行干预可能有助于AD患者BPSD的防治。     

氯氮平和经典抗精神病药的长期治疗对患者体重、糖代谢及血脂的影响

目的 探讨长期应用氯氮平和经典类抗精神病药(APS)对精神分裂症患者体重、血糖和血脂等代谢指标的影响及其可能的相关因素.方法 共调查使用APS≥5年的精神分裂症患者271例,分别测量其身高和体重,检测空腹和餐后2h血糖、空腹血清游离脂肪酸、血清胰岛素和瘦素水平.按药物使用情况将患者分为氯氮平组、经典APS单一治疗组(经典组)或联合用药组进行比较.结果 [1]联合用药组体质量指数、空腹血糖、血甘油三酯和血游离脂肪酸水平均显著高于经典组(P＜0.05);血胰岛素和胰岛素抵抗指数也均显著高于经典组和氯氮平组(P＜0.05).[2]氯氮平组和联合用药组糖耐量降低和2型糖尿病发生率均明显高于经典组(P＜0.05).[3]患者体质量指数与其空腹血糖、血清瘦素、血甘油三酯、胆固醇水平以及与胰岛素抵抗指数均呈正相关(P均小于0.05);患者血清瘦素水平与其血胰岛素水平也呈正相关(P=0.008).[4]多元逐步线型回归分析表明,进入影响空腹血糖水平方程的因素分别为胰岛素抵抗指数、血胰岛素、胆固醇和体质量指数(P＜0.05).结论 单用氯氮平及其与经典抗精神病药联用,均易导致患者肥胖,且易导致患者血糖、血脂、血游离脂肪酸水平升高,并与胰岛素抵抗和糖耐量降低发生相关,可能增加2型糖尿病的发生.     

脑梗死与代谢综合征的相关性研究

目的 探讨代谢综合征(metabolic syndrome,MS)及其各单一组分危险因素对不同类型脑梗死(cerebral infarction, CI)的影响.方法 选择符合纳入标准的脑梗死454例,其中血栓性脑梗死(cerebral thrombosis,CT)244例,腔隙性脑梗死(lacunar infarct, LI)210例及对照组300例.分析各组MS的患病率,MS及其各单一组分危险因素与不同类型脑梗死的相关性.结果 (1)脑梗死组MS患病率50.22%(228/454),CT组及LI组分别为54.10%(132/244)、45.71%(96/210),均显著高于对照组25.33%(76/300).(2)CT组除肥胖外,MS各单一组分危险因素的患病率均高于对照组,LI组仅高血压、高血糖、甘油三酯(TG)增高及高密度脂蛋白胆固醇(HDL-C)降低的患病率高于对照组,且两类脑梗死的高血糖、高血压患病率有显著差异.(3)调整年龄、性别和其他脑卒中危险因素后,代谢综合征依然增加脑梗死患病的危险,按CDS标准对上述两类脑梗死的OR 值分别为2.84 (95%CI : 1.85～5.62)、2.02 (95%CI: 1.32～4.13).(4)两类脑梗死的胰岛素抵抗指数均(HOMAIR)高于对照组,随着组成MS危险因素的增加,HOMAIR逐渐升高.结论 MS与脑梗死患病危险增加相关,这种关系独立于脑卒中的其他危险因素.MS及其各单一组分的危险因素对不同类型脑梗死所起作用有所差别.MS的发生与胰岛素抵抗有关.     

餐后高甘油三酯血症与胰岛素抵抗关系分析

目的:探讨高甘油三酯血症与胰岛素抵抗(IR)的关系。方法:56例青年男性分为试验组和对照组(各28例),试验组行脂肪耐量试验。两组于空腹、餐后3、8h分别采血,测定甘油三酯(TG)、高密度脂蛋白-胆固醇(HDL-C)、血糖(GLU)、胰岛素(INS)水平,并计算3个时间点胰岛素敏感性指数(ISI,=log(1/GLU.INS))。结果:试验组有4/28存在富含甘油三酯脂蛋白(TRL)清除延迟。3/4TRL清除延迟者餐后8h,ISI均值低于试验组餐后3h均值;试验组在餐后3h高TG/低HDL-C应答同时,ISI降低(与空腹及对照组相比P<0.01)。提示产生胰岛素抵抗(IR)现象。结论:餐后高TG/低HDL-C/TRL清除延迟是一组动脉粥样硬化相关脂蛋白表型;可导致胰岛素抵抗。合理膳食、防治高TG血症是解决这些问题的根本措施。提出甘油三酯代谢紊乱综合征的概念,认为甘油三酯代谢紊乱综合征是代谢水平脂质紊乱和多种动脉粥样硬化相关危险因素的病理基础。     

胰岛素抵抗对2型糖尿病患者周围神经病变的影响

目的探讨及分析胰岛素抵抗对2型糖尿病患者周围神经病变的影响。方法选取2型糖尿病患者161例为研究对象,按照是否合并周围神经病变将患者分为糖尿病周围神经病变组(DPN组,n=102)和非糖尿病周围神经病变组(NDPN组,n=59);比较2组一般资料、餐后胰岛素敏感性(Matsuda指数)、空腹胰岛素抵抗(HOMA-IR)、空腹及糖耐量实验(OGTT)后各时间点的血糖、胰岛素素及C-肽水平之间的差异。结果 DPN组年龄、糖尿病病程、HbA1c、LDL-C水平均高于NDPN组,差异有统计学意义(P0.05),Matsuda指数、HOMA-IR、空腹血糖及胰岛素水平[OGTT(0 min)]均高于NDPN组(P0.05),OGTT(120min)胰岛素水平显著低于NDPN组(P0.05);Logistic回归分析提示:年龄、空腹血糖(FBG)、胰岛素(FIRI)水平、HOMA-IR、Matsuda指数与患者周围神经病变的发生呈正相关(P0.05),而OGTT(120min)胰岛素水平与其呈负相关(P0.05)。结论 2型糖尿病患者空腹胰岛素抵抗与周围神经病变的发生密切相关,而患者餐后胰岛素抵抗则可能对周围神经病变的发生起到抑制作用。     

精神分裂症患者发生代谢综合征危险因素研究

目的 探讨精神分裂症患者代谢综合征发生的危险因素,方法 以是否发生代谢综合征为标准,将84例单一服用氯氮平治疗的精神分裂症患者分为两组,其中代谢综合征组36例,非代谢综合征组48例.收集患者的一般资料,包括性别,年龄,吸烟史,教育程度,婚姻状况,服药剂量,服药时间,晨起空腹状态下测定患者的体重,身高,腰围,血压,空腹血糖,总胆固醇,甘油三酯,低密度脂蛋白,高密度脂蛋白,C-反应蛋白,IL-6,比较分析两组一般资料和所测定指标的差异.结果 代谢综合征组患者的吸烟率(P=0.006),腰围(P=0.001),空腹血糖(P＜0.001),甘油三酯(P=0.008),C-反应蛋白(P＜0.001)和白介素-6 (P＜0.001)水平明显高于非代谢综合征组,两组间差异具有统计学意义.以是否发生代谢综合征为因变量,建立Logistic回归模型,血糖(95％ CI,OR:5.5,27.03),收缩压(95％CI,OR:1.84,2.39),年龄(95％ CI,OR:1.17,1.37),腰围(95％ CI,OR:1.83,3.07),甘油三酯(95％ CI,OR:23.08,45.26),C-反应蛋白(95％ CI,OR:1.08,2.94)这6个变量进入回归方程.结论 发生代谢综合征的精神分裂症患者,具有更高的吸烟比率,腰围,空腹血糖,甘油三酯和C-反应蛋白水平,而空腹血糖,收缩压,年龄,腰围,甘油三酯和C-反应蛋白是代谢综合征发生的独立危险因素,可以作为预测指标,做到代谢综合征的早期预防和干预.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.