鬼臼毒素纳米脂质载体的制备及质量考察*★

目的：纳米脂质载体是近年来继固体脂质纳米粒发展起来的第2代亚微粒载药系统，具有较高的载药量和物理稳定性。探讨鬼臼毒素-脂质纳米粒（podophyllotoxin-loaded nanostructured lipid carrier，PPT-NLC）的制备方法及理化性质。 方法：实验于2006-08/2007-10在南方医科大学药学部实验室完成。选择固体脂质硬脂酸、单硬脂酸甘油脂和液态脂质油酸，采用改良的乳化蒸发-低温固化法制备PPT-NLC，用同法制备不含油酸的PPT-固体脂质纳米粒(Solid lipid nanoparticles，SLN)纳米粒混悬液。用透射电镜、Zeta电位仪、高效液相色谱法、pH计考察PPT-NLC理化性质，并比较SLN与NLC的包封率和稳定性。 结果：透射电镜下PPT-NLC外形呈圆形或椭圆形，平均粒径为（88.2±8.4）nm，多分散指数为0.190±0.085，Zeta电位为（-33.2±3.1）mV，包封率为86.6%。PPT-SLN分别为（75.3±16.2）nm，0.300±0.072，（-25.2±3.4）mV，包封率为76.5%。 结论：PPT-NLC制备工艺简单，分布均匀，稳定性较SLN好，包封率高。     

正交优化聚乳酸-羟基乙酸纳米粒的制备

摘要 背景：聚乳酸-羟基乙酸纳米粒或纳米微球用于制备生物降解型缓释或定向给药体系已经研究了近30年,是国内外研究的热点。该体系能够控制粒径大小、延缓药物降解、延长药物释放时间、靶向释放、降低药物毒性和刺激性等。 目的：以紫杉醇为模型药物、聚乳酸-羟基乙酸为包裹材料,探索载药纳米粒的制备条件对粒径、包封率等的影响,确定最佳制备工艺条件。 方法：采用乳化-溶剂挥发法制备聚乳酸-羟基乙酸纳米粒,以粒径、包封率和载药量等为观察指标,通过正交设计法优化纳米粒制备工艺条件。 结果与结论：通过正交实验设计,优化了制备工艺条件,其最佳条件是超声乳化时间为15 min,乳化剂浓度为1%,油水相比为1∶25,合成温度为25 ℃。在此条件下进行实验,制备出的载药纳米粒粒径为217.6 nm,载药量1.79%,包封率85%。该制备工艺简单、稳定,优化制备条件,可制备出包封率高、粒径适宜的紫杉醇-聚乳酸-羟基乙酸纳米粒。 关键词：聚乳酸-羟基乙酸;紫杉醇;纳米粒;正交实验;缓释 doi:10.3969/j.issn.1673-8225.2010.42.009     

负载紫杉醇壳聚糖纳米粒的制备、表征与释药性能

背景：紫杉醇是一种天然抗肿瘤药物,但其水溶性极低。壳聚糖经接枝改性，生成的共聚物可在液相中生成纳米粒，可用于药物的缓释和控释。 目的：对制备的负载紫杉醇的壳聚糖纳米粒进行表征，分析其体外药物释放能力。 设计、时间及地点：重复测量设计，于2008-01/07在华北煤炭医学院医学系实验室完成。 材料：壳聚糖，平均相对分子质量为2.0×105，脱乙酰度为92%，为浙江省玉环海洋生物化学有限公司产品。紫杉醇，批号082329802，为中国药品生物制品检定所产品。 方法：采用引发接枝效率高、引发反应条件温和的二羟基二过碘酸合镍钾为引发剂，在壳聚糖上接枝醋酸乙烯酯，该聚合物在水溶液中直接生成具有疏水核心、亲水表面的纳米粒，即壳聚糖纳米粒，再利用超声振荡技术将0.5~5.0 mg紫杉醇与上述纳米粒混合制成负载紫杉醇的壳聚糖纳米粒。 主要观察指标：激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位，透射电镜观察纳米颗粒的外观形态，高效液相色谱法分析负载紫杉醇的壳聚糖纳米粒的包封率、载药量和释药性能。 结果：壳聚糖纳米粒和负载紫杉醇的壳聚糖纳米粒，其粒径分别为196.2 nm和320.8 nm，粒径分布较窄，纳米粒表面均带正电荷，Zeta电位比较差异无显著性意义（F=0.818，F=3.38，P均>0.05）。稳定的纳米粒呈球形，粒径均匀。紫杉醇的加入量可影响纳米粒的包封率，紫杉醇的加入量为纳米粒的量2%时，达到最大包封率93.6%。体外模拟释药结果表明药物释放曲线分为两个阶段，突释阶段微球释药量在24 h内达48.3%，缓释阶段微球释药持续时间长，在175 h时释药量达75.9%，载药纳米粒的药物释放速率持续稳定。 结论：接枝共聚法制备壳聚糖纳米粒简便可靠，负载紫杉醇后纳米粒径明显变大，表面带有正电荷，且纳米粒对紫杉醇有很高的包封率，体外释药具有明显的缓释作用。     

负载两性霉素B壳聚糖-聚乳酸纳米粒的制备及其释药性能*☆

背景：两性霉素B为治疗深部真菌感染的首选药物,但该药无法通过血脑屏障而对隐球菌性脑膜炎的治疗效果甚微。利用纳米粒子作为药物载体的优势,通过相分离透析技术制备负载两性霉素B的壳聚糖-聚乳酸纳米粒子,有望克服两性霉素B的不足。 目的：对负载两性霉素B的壳聚糖-聚乳酸纳米粒进行表征,分析其体外药物释放能力。 设计、时间及地点：重复测量设计,于 2008-11/2009-04 在国家纳米科学中心纳米医学与生物实验室完成。 材料：壳聚糖,平均相对分子质量为3.4×105,脱乙酰度为93%,为上海卡伯工贸有限公司产品。两性霉素B为Sigma公司产品。 方法：在二甲基亚砜溶液中,在三乙胺存在下,通过壳聚糖和D,L-丙交酯的开环聚合反应能够生成壳聚糖-聚乳酸共聚物。该共聚物由亲水壳聚糖段和疏水聚乳酸段组成,在水中能够组装形成纳米粒子。两性霉素B通过相分离透析技术包载于纳米粒子中。 主要观察指标：激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布,环境扫描电镜观察纳米颗粒的外观形态,紫外光谱分析负载两性霉素B的壳聚糖-聚乳酸纳米粒的包封率、载药量和释药性能。 结果：壳聚糖-聚乳酸纳米粒和负载两性霉素B的壳聚糖-聚乳酸纳米粒,其粒径分别为114 nm和153 nm(当丙交酯与壳聚糖摩尔比为11∶1时)。纳米粒子粒径分布较窄,呈球形。共聚物中丙交酯与壳聚糖摩尔比影响药物的包封率和载药量,随着丙交酯与壳聚糖摩尔比从11∶1到20∶1,包封率从(62.3±3.5)%增加到(90.7±2.8)%,载药量从(7.8±1.2)%增加到(12.3±1.4)%。随着聚乳酸段质量比增加,纳米粒子尺寸、包封率和载药量增加,而药物释放降低。 结论：开环聚合制备壳聚糖-聚乳酸共聚物及用相分离透析方法制备负载两性霉素B纳米粒简便可靠,负载两性霉素B后纳米粒径明显变大,且纳米粒对两性霉素B有很高的包封率,体外释药具有明显的缓释作用。 关键词：两性霉素B;壳聚糖;聚乳酸;纳米粒子;包封率;体外释放     

壳聚糖-siRNA纳米粒的制备及其特征分析

目的 探讨离子凝胶法制备壳聚糖（CS）-siRNA纳米粒的特点，并分析其理化性质。方法 将CS、三聚磷酸钠（TPP）和siRNA通过离子凝胶法制备CS—siRNA纳米粒：透射电镜观察其形态，zeta电位／粒度分析仪测定纳米粒的平均粒径和zeta电位；分光光度计测定上清中siRNA含量．计算包封率、siRNA的体外控释能力；凝胶电泳分析与胎牛血清作用后纳米粒中siRNA的稳定性。结果 成功制备的CS—siRNA纳米粒经电镜观察发现纳米粒呈球形，大小均匀；zeta电位／粒度分析仪测定其平均粒径为83．3nin．zeta电位＋24．2mV；包封率为95％，24h内siRNA的体外释放率不足20％；电泳结果表明CS—siRNA性质稳定，能够阻止RNase对siRNA的降解，具有保护siRNA的作用。结论 离子凝胶法制备CS—siRNA纳米粒方法简单、条件温和，包封率高、稳定性好：纳米粒体外能显著延缓siRNA释放，保护siRNA免受降解。     

乳酸-羟基乙酸共聚物载药纳米粒的制备及体外释药性

摘要 背景：医用纳米粒作为药物传递的新型载体,目前已经成为医药领域研究的重点。 目的：构建以生物可降解材料乳酸-羟基乙酸共聚物为载体,负载抗肿瘤药物5-氟尿嘧啶的载药纳米粒。 方法：利用复乳-溶剂挥发法制备乳酸-羟基乙酸共聚物载药纳米粒。场发射扫描电子显微镜观察纳米粒表面形态;激光粒度分析仪测定粒径分布并计算成球率;紫外分光光度计测定5-氟尿嘧啶载药量、包封率,并对体外释药进行评估。 结果与结论：纳米粒呈球性,平均粒径为(186±14) nm,成球率、载药量和包封率分别为70.8%、6.6%、28.1%,体外释药有突释现象,24 h内5-氟尿嘧啶累积释药量达36.2%,10 d达83.6%。提示成功制备乳酸-羟基乙酸共聚物载药纳米粒,其具有缓释效应。 关键词：乳酸-羟基乙酸共聚物;5-氟尿嘧啶;纳米粒;体外释药;缓释 doi:10.3969/j.issn.1673-8225.2011.16.017     

载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜的制备及体外释药评价

背景：纤维蛋白胶胶联羊膜作为一种无需缝合生物移植材料还无法有效地在局部长时间缓释药物,特别是对于一些不稳定的生物活性蛋白药物。 目的：构建新型的能有效缓释蛋白药物的载表皮生长因子壳聚糖纳米粒纤维蛋白胶羊膜复合体。 方法：制备表皮生长因子/壳聚糖载药纳米粒并考察其表征,然后将载药纳米粒掺入纤维蛋白胶,再将载纳米粒的纤维蛋白胶和羊膜胶联黏合,制备出负载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜,并进行形态学和体外释药观察,检测释放出的表皮生长因子生物活性。 结果与结论：表皮生长因子/壳聚糖纳米粒的粒径为(275.7±6.8) nm,Zeta电位为(32.7±0.6) mV,包封率为(67.03±1.22)%,多分散指数为0.23±0.04,形态圆形均一,载纳米粒纤维蛋白胶能够很好地与羊膜胶联黏合,表面呈网状结构,纳米粒充斥其中。载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜体外释药可达14 d,释放的表皮生长因子生物活性可保持7 d以上。说明制备的载重组人表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜作为一种无缝合生物移植材料可在局部缓慢释放表皮生长因子。     

磁性聚乳酸羟基乙酸氧化酚砷纳米微粒的制备及其特性**★

背景：基于纳米技术发展起来的纳米载体介导的磁性载药系统，在外加磁场作用下，能实现位点特异性靶向给药的目的，有利于提高病灶部位的局部药物浓度，从而进一步提高治疗效果，减少全身毒副作用。 目的：研究磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒的制备工艺，评价纳米粒子特性。 设计：首先选择几个可能影响纳米微粒特性的因素进行了单因素实验，然后再根据实验结果，结合统计学中的正交设计，获得了最佳优化处方。 单位：解放军第二军医大学长海医院特诊科。 材料：实验于2005-01/2006-03在解放军第二军医大学药学院药剂教研室完成。实验用氧化酚砷购自美国Sigma公司，聚乳酸-羟基乙酸由山东医疗器械研究所提供，纳米级四氧化三铁购自美国Sigma公司，聚乙烯醇购自北京有机化工厂，二氯甲烷等其他试剂均为分析纯，购于上海国药集团化学试剂有限公司。 方法：运用超声乳化-溶剂挥发法制备磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒，通过透射电镜观察微粒形态，振动样品磁强计确证纳米微粒磁性的存在，激光粒径仪测定纳米粒的粒径大小和分布，高效液相法测定氧化酚砷的载药量及包封率,并计算氧化酚砷体外释放百分率。 主要观察指标：磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒的形态、粒径、载药量、包封率、磁性及体外释放情况。 结果：①微粒包封率和载药量：实验制备的纳米粒平均包封率为34.2%；5批纳米粒载药量分别为3.06%，3.15%，3.18%，3.21%，3.41%，平均载药量为3.20%，批间差异较小，说明工艺稳定性、重现性好。②微粒形态：纳米微粒呈圆形，表面光滑，分布均匀，不粘连，磁性微球中可见非均匀分散的黑色不透光区，为四氧化三铁微粒。③微粒粒径：分布范围窄（140~500 nm）,平均290 nm。④微粒磁性：在不断改变外加磁场的大小与方向的情况下，微粒具有不同的磁化强度，说明氧化酚砷聚乳酸纳米微粒具有一定的磁响应性。⑤体外释放实验：氧化酚砷经过最初的快速释放后，进入缓慢控释阶段，于第8天时达到最终基本稳定的平台期。 结论：实验获得了较满意的磁性聚乳酸-羟基乙酸氧化酚砷纳米微粒制备工艺；该纳米微粒在外加磁场的情况下有较好磁靶向性的作用，同时具备良好药物缓释作用。     

鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察*★

目的：制备含有不同冻干保护剂的鬼臼毒素固体脂质纳米粒(POD-SLN)冻干粉，并考察其理化性质，筛选出最佳配方。 方法：实验于2006-12/2007-11在南方医科大学药学部实验室完成。冻干配方为15%海藻糖、15％甘露醇和二者联用各取 5％，冷冻干燥制作冻干粉制剂。扫描电镜下观察冻干粉复溶后粒子形态，Image -Pro Plus 6.0软件计算粒径大小，高效液相考察固体脂质纳米粒的药物包封率，并考察冻干粉的外观、复溶和4 ℃保存对其影响，评价不同辅料对冻干品的影响。 结果：①外观和复溶情况：海藻糖冻干粉、海藻糖联用甘露醇冻干粉表面均松脆多孔，疏松，复溶较快，约需20 s，甘露醇冻干粉表面较光滑，结构致密，饼状，复溶较慢，需借助外力。冻干粉样品4 ℃冰箱放置24 h、1，3，6个月其外观和复溶均无明显变化。②电镜下粒子形态：呈圆形或椭圆形，分布较均匀，冻干前后无明显差异。③粒径：未加冻干保护剂时为（82.65± 18.43）nm，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为（94.78±21.94），（109.26±16.15），（114.63±21.42）nm。④包封率：未加冻干保护剂时为 87.4%，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为86.2%，80.3%，79.6%。 结论：以15%海藻糖为冻干保护剂制备的鬼臼毒素固体脂质纳米粒冻干粉粒径较小，包封率高，稳定性好，其制备工艺合理可行。     

改良自乳化溶剂扩散法制备MePEG-PLA纳米粒对成骨细胞的毒性*

两亲性嵌段聚合物由于其较强的载药能力强、纳米级大小、血液中长循环等优点在载药系统中得到广泛的应用。 目的：评估改良自乳化溶剂扩散法制备的甲氧基封端的聚乙二醇-聚乳酸 (MePEG-PLA)纳米粒对人骨肉瘤细胞MG63的毒性。 方法：通过改良自乳化溶剂扩散法制备MePEG-PLA纳米粒,MTS法测定纳米粒培养1,2,3 d后对MG63的毒性。激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位;透射电镜表征纳米胶束外观形态;酶标仪检测培养1,2,3 d细胞吸光度值。 结果与结论：MePEG-PLA纳米粒的平均粒径为25.7 nm,分布均匀,呈球形,Zeta电位为-8.06 mV,MePEG-PLA毒性为 0级。提示改良自乳化溶剂扩散法制备纳米粒简单易行,制备的纳米粒无毒,具有良好的应用前景。     

Effects of Alpha- and Beta-Adrenergic Agonists and Antagonists on Growth Hormone Secretion in Man

It is well known that the adrenergic system has both stimulatory and inhibitory influences on growth hormone (GH) secretion probably by modulating GH-releasing hormone (GHRH) and/or somatostatin release. To better understand the mechanisms by which these influences take place, we investigated the effects of α- and β-adrenergic agonists and antagonists on both basal and GHRH-induced GH release in 23 male adult volunteers. The GH-releasing effect of clonidine (0.15 mg infused iv over 10 min), an α₂-adrenergic agonist, was significantly blunted by yohimbine (30 mg orally at ?50 min), a relatively specific α₂-adrenergic antagonist area under the response curve, mean±SEM: 672.6 ± 143.0 versus 219.6 ± 16.7 μg/l/h; P<0.05). On the other hand, the GHRH (1 μg/kg iv as a bolus)-induced GH increase was unaffected by yohimbine (339.3 ± 19.1 versus 518.1±172.8 μg/I/h). Concomitant blockade of α₁-/α₂-adrenoreceptors by phentolamine (0.5 mg/ml/min infused iv from ?60 to +30 min) abolished the GHRH-induced GH rise (645.5± 106.0 versus 189.0±58.8 μg/l/h; P<0.01). Finally, the GHRH-stimulated release was blunted by β₂-adrenergic stimulation with salbutamol (10 μg/min infused iv from ?5 to +15 min) (324.3 ± 99.7 versus 112.7 ± 48.8 μg/l/h; P<0.02). In conclusion: 1) The evidence that yohimbine is able to blunt the clonidine-induced GH release but fails to inhibit the GHRH-induced GH rise indicates that, as in animals, in man too the GH-releasing effect of clonidine is specifically mediated by α₂-receptor activation, and may occur via endogenous GHRH release; 2) the inhibitory effect on GH release of β, namely β₂, receptor activation is probably mediated by the somatostatinergic system; 3) an unopposed β-adrenergic activation would account for the inhibitory effect on GHRH-induced GH release of concomitant α₁–/α₂-adrenoreceptor blockade by phentolamine.     

Metabolic imprinting by maternal protein malnourishment impairs vagal activity in adult rats

Protein restriction during lactation has been suggested to diminish parasympathetic activity, whereas sympathetic activity is enhanced in adult rats. The present study analyses whether dysfunction of the autonomic nervous system is involved in the impairment of insulin secretion from perinatally undernourished rats. Male neonates were reared by mothers fed a low‐ (4%) protein (LP group) or normal‐ (23%) protein diet (NP group). At 81 days of age, LP rats showed less body mass than NP rats (318 ± 4 g versus 370 ± 5 g) (P < 0.001). Fat tissue accumulation decreased in LP [0.8 ± 0.03 g/100 g body weight (BW)] compared to NP rats (1.1 ± 0.04 g/100 g BW) (P < 0.001). LP were glucose‐intolerant as registered by the area under the curve of an i.v. glucose tolerance test (37 ± 3) compared to NP rats (29 ± 2) (P < 0.05); however, LP animals showed fasting normoglycaemia (LP, 5.0 ± 0.1; NP, 4.9 ± 0.03 mm ) and hypoinsulinaemia (LP, 0.10 ± 0.02 ng/ml; NP, 0.17 ± 0.02 ng/ml). LP also showed glucose tissue uptake 60% higher than NP rats (P < 0.05). Vagus firing rate from LP was lower (7.1 ± 0.8 spikes/5 s) than that in NP rats (12.3 ± 0.7 spikes/5 s) (P < 0.001); however, there was no difference in sympathetic nervous activity. The cholinergic insulinotrophic effect was lower in pancreatic islets from LP (0.07 ± 0.01 ng/min/islet) than in NP rats (0.3 ± 0.06 ng/min/islet), whereas the levels of adrenaline‐mediated inhibition of glucose‐induced insulin release were similar. Perinatal protein restriction inhibited the activity of the vagus nerve, thus reducing the insulinotrophic effect of parasympathetic pathways on pancreatic β‐cells, which inhibit insulin secretion.     

两亲性壳聚糖衍生物负载及缓释醋酸曲安奈德的性能

背景：醋酸曲安奈德是一种长效肾上腺糖皮质激素，具有较强的抗炎作用。近年来在眼内疾病的治疗中取得了较好的效果，但同时带来一些不良反应，且需多次注射，以防止疾病复发。壳聚糖经接枝改性，生成的共聚物可在水溶液中生成纳米粒，用于药物的缓释载体，延长药物作用时间，降低不良反应，提高生物利用度。 目的：合成含脱氧胆酸基团的两亲性壳聚糖衍生物作为醋酸曲安奈德的载体材料，制备具有缓释功能的载药纳米胶束，研究其负载和缓释醋酸曲安奈德的性能。 方法：通过酰胺化反应在壳聚糖上偶联脱氧胆酸基团，合成两亲性壳聚糖衍生物。透射电镜观察纳米粒的外观形态和粒径，Zeta电位分析仪测定纳米粒的Zeta电位，体外释放实验检测负载醋酸曲安奈德的壳聚糖-脱氧胆酸纳米粒的包封率、载药量和体外释药性能。 结果与结论：合成出含脱氧胆酸基团的两亲性壳聚糖衍生物，它能与醋酸曲安奈德形成载药纳米胶束，载药量可高达82%。随着载药量的增加，载药纳米胶束的粒径逐渐增大，而Zeta电位则呈下降的趋势。体外释放的结果表明载药纳米胶束能起到72 h缓释醋酸曲安奈德的作用。提示以两亲性壳聚糖衍生物为载体的载药纳米胶束显示出较好的缓释醋酸曲安奈德性能，将有希望提高醋酸曲安奈德的治疗效果。 关键词：醋酸曲安奈德；两亲性壳聚糖衍生物；脱氧胆酸；纳米胶束；体外药物释放 doi:10.3969/j.issn.1673-8225.2010.29.013     

The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat

Tissue concentration of norepinephrine and neuropeptide-Y immunoreactivity (NPY-IR) were measured in the urinary bladder, urethra, prostate and corpus cavernosum of the spontaneously hypertensive rat, as well as the normotensive Wistar-Kyoto rat. sho results showed significantly increased tissue norepinephrine concentrations in the urinary bladder, urethra and prostate of the spontaneouly hypertensive rat when compared to those of the normotensive rat (hypertensive, n = 18: 18.3 ± 2.1, 14.9 ± 1.7, 22.6 ± 2.3 vs. normotensive, n = 18: 11.2 ± 1.9, 10.4 ± 1.3, 16.7 ± 2.4 nmol/g tissue, respectively, P < 0.05 in each case). No difference was noted in the cavernosal tissue (hypertensive, n = 18: 11.3 ± 1.6 vs. normotensive, n = 18: 10.1 ± 1.8 nmol/g tissue, P > 0.01). Correspondingly, tissue NPY-IR was significantly increased in the bladder, urethra and prostate tissue of the spontaneously hypertensive rat (hypertensive, n = 18: 39.7 ± 5.6, 25.3 ± 3.4, 31.5 ± 2.8 vs. normotensive, n = 18: 27.4 ± 3.1, 18.6 ± 2.7, 24.2 ± 3.2 pmol/g tissue, respectively, P < 0.05 in each case). Again, no significant difference was observed in the cavernosal tissue (hypertensive, n = 18: 15.9 ± 2.2 vs. normotensive, n = 18: 14.8 ± 2.6 pmol/g tissue, P > 0.01). It is therefore concluded that increased tissue concentration of norepinephrine and NPY-IR were present in the urinary bladder, urethra and prostate of the spontaneously hypertensive rat. The significance of such biochemical findings needs further investigation but may suggest increased sympathetic innervation or activity. On the contrary, no corresponding changes were observed in the corpus cavernosum of the hypertensive rat.     

Activation and suppression of the sternocleidomastoid muscle induced by transcranial magnetic stimulation

Responses in the sternocleidomastoid muscle (SCM) induced by transcranial magnetic stimulation (TMS) were investigated in 10 healthy subjects. Stimuli were given with the Dantec MagLite™ magnetic stimulator using a 12.5 cm circular coil with counter-clockwise current direction. Monopolar needle electrodes with isolated shafts were used for simultaneous bilateral electromyographic (EMG) recordings of the SCM. TMS given on either side invariably induced an ipsilateral motor evoked potential of the SCM (SCM-MEP), whereas a contralateral SCM-MEP was just seen in 25% of the performed stimulation series also when maximal intensity was used. The SCM-MEPs recorded ipsilaterally to the side of stimulation had significantly higher maximal amplitudes (P < 0.05) compared to the SCM-MEPs recorded contralaterally (mean ± S.D.: 1.0 ± 0.5 and 0.2 ± 0.1 mV, respectively). These results support the concept of a predominantly ipsilateral control of SCM activation. The contralateral SCM-MEPs tended to have a shorter latency than the ipsilateral SCM-MEPs. The thresholds of the ipsilateral SCM-MEPs were significantly higher (P < 0.01) on the left side than on the right side (mean ± S.D.: 78 ± 18 and 60 ± 16 A/μsec, respectively), which could be due to the consistent use of counter-clockwise coil current direction. TMS given on either side induced suppression of voluntary SCM activity in all investigated subjects. Responses induced by TMS given ipsilaterally and contralaterally to the voluntary activated muscle did not differ significantly (P ≥ 0.05) regarding threshold or latency of the suppression.     

A double‐blind,placebo‐controlled trial of rosiglitazone for clozapine‐induced glucose metabolism impairment in patients with Schizophrenia

Objective: The primary purpose of this 8‐week double‐blind, placebo‐controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine‐treated subjects with schizophrenia with insulin resistance. Method: Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results: Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non‐significant improvement in SG (0.016 ± 0.006–0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8–7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low‐density lipoprotein cholesterol (LDL‐C) particle number (987 ± 443–694 ± 415, effect size = 0.30, P = 0.04). Conclusion: Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.