Preparation and characterisation of the colistin-entrapped liposome driven by electrostatic interaction for intravenous administration

Potential use of liposome for polycationic colistin is hindered by their phospholipid membrane permeability. In this study, liposomes were modified with sodium cholesteryl sulphate (Chol-SO₄^?) for improving the colistin loading by enhancing the colistin-bilayer electrostatic attraction. We have evaluated two liposomes: colistin-entrapped liposome of Chol-SO₄^? (CCL) and coated Chol-SO₄^?/colistin complex liposome (CCCL). In comparison with CCL which formed large aggregates at Chol-SO₄^?/colistin charge ratio below 2:1, CCCL showed a smaller size less dependent on the charge ratio, probably arising from more colistin entrapped on the inner leaflet of bilayer. Both liposomes exhibited significantly increased entrapment efficiency as compared with the liposome without Chol-SO4^?. But colistin released upon dilution, implying free transfer of colistin through bilayers. Pharmacokinetics results showed the approximately four-fold increase in the plasma AUC_0–8?h for CCCL and CCL as compared with colistin solution, showing potential benefit for infectious target localisation by prolonging the systemic circulation of colistin.     

多囊卵巢综合征患者口服炔雌醇环丙孕酮片致过敏反应

摘 要 目的：探讨临床药师在多囊卵巢综合征患者口服炔雌醇环丙孕酮片抗雄激素治疗中出现过敏反应的处理方法及药学监护。方法: 临床药师通过综合分析患者过敏史及用药史,结合患者用药时间和不良反应的发生时间,判断所用药物与过敏反应的相关性,并对其后续治疗替代药物提出用药建议。结果: 最终判定炔雌醇环丙孕酮片与此次不良反应的关联性评价为很可能,其中两种成分炔雌醇和醋酸环丙孕酮都不能排除为此次过敏反应的发生原因,建议选用屈螺酮炔雌醇片或含天然雌激素成分的口服避孕药进行后续替代治疗。结论:临床药师针对药物致过敏反应展开的病例分析及药学监护,有助于促进多囊卵巢综合征患者的个体化治疗,在保证用药安全,提高患者依从性方面发挥重要作用。     

尼莫地平缓释胶囊相对生物利用度的研究

12例健康志愿者随机交叉口服进口尼莫地平普通片和尼莫地平缓释胶囊60mg后, 利用高效液相色谱法测定血药浓度并对其生物利用度进行了研究.尼莫地平缓释胶囊和进口片的T1/2分别为3.74±0.84 h和1.98 ± 0.59 h;Cmax分别为25.41±9.32mg·L-1和80.08±16.65 mg·L-1; Tmax分别为3.25±0.97 h和0.75±0.21 h; AUC分别为167.4±27.3 mg·h·L-1和 194.7 ± 29.7mg·h·L-1;缓释胶囊的相对生物利用度为87.07%±9. 19%.8 例健康志愿者随机交叉多剂量口服尼莫地平缓释胶囊(60 mg,bid) 和尼莫地平普通片(30 mg,qid),达稳态时测得峰浓度分别为25.81±7.12 mg·L-1 和 41.21±10.04 mg·L-1; 谷浓度分别为7.19±1.84 mg·L-1和5.59 ± 1. 62 mg·L-1;两者血药浓度的波动系数分别为1.12±0.16和1.51±0.17.     

A Coupled CFD-DEM Study on the Effect of Basset Force Aimed at the Motion of a Single Bubble

The physical meaning of Basset force is first studied via polynomial approximation and the Fourier series representation method. After compiling the Basset force into the coupling interface with Visual C, a dynamic mathematical model is set up to describe the upward motion behavior of a single bubble by adopting the CFD-DEM method. Afterwards, the coupling interface with Basset force proposed in this study is verified experimentally and shows very good agreements. The initial velocity, releasing depth, bubble size, density ratio and viscosity ratio are studied qualitatively due to their great importance to Basset force. The ratio of Basset force to the sum of Basset force and drag force and to buoyancy, F→Ba/(F→D+F→Ba) and |F→Ba/F→B|, are employed to quantify the contribution of Basset force quantitatively. In addition, some instructive outlooks and recommendations on a further development of appropriate and justifiable use of Basset force are highlighted at last.     

甲状腺素对豚鼠耳蜗毛细胞的保护作用

应用耳蜗外淋巴灌流技术、微电极技术及扫描、透射电镜技术，观察先服甲状腺素（10mg)三次后行外淋巴灌流卡那霉素（10^-3g/ml)1小时的豚鼠实验组（T／K）蜗内电位（EP），耳蜗微音电位（CM）和毛细胞的亚微结构变化，并与单纯灌流卡那霉素（10^-3g/ml)的豚鼠对照组（KM）进行比较，发现3组动物EP无明显差异；实验组（T／K）的CM下降较对照组（KM）少，两者有显著差异；实验组动物外毛细胞损伤较对照组动物轻，提示甲状腺素可能直接作用于听毛细胞，减轻卡那霉素对内耳的毒副作用。     

利尿酸与庆大霉素耳毒作用协同影响的实验研究

通过给72只豚鼠分别单独注射利尿酸（EA)、庆大霉素（GM）和合并注射EA、GM后，观察三组豚鼠前庭功能、听力改变、血清和外淋巴中庆大霉素浓度以及内耳显微和亚显微结构的改变，发现合并使用利尿酸和庆大霉素可以加重庆大霉素耳中毒，其可能原因为利尿酸增加了庆大霉素在外淋巴中的蓄积。     

语前聋患儿国产人工耳蜗植入效果分析

目的 观察语前聋患儿植入诺尔康-晨星人工耳蜗(Nurotron-Venus cochlear implant,Nurotron-Venus CI)后的听觉言语发育情况及其安全性和稳定性.方法 回顾性分析郑州大学第一附属医院行Nurotron-Venus CI植入的78例语前聋患儿的临床资料,患儿植入年龄为13~96月,按植入年龄将患儿分为 A组(13~24月,16 例)、B 组(25~36月,13 例)、C组(37~48月,16 例)、D 组(49~72月,18 例)、 E 组(73~96月,15 例);在患儿术前及开机后1、3、6、12个月采用有意义听觉整合量表(meaningful auditory integration scale,MAIS)(C、D、E组)、婴幼儿有意义听觉整合量表(infant-toddler meaningful auditory integration scale,IT-MAIS )(A、B组)进行听觉能力评估,开机后1、3、6、12个月使用有意义言语使用量表(meaningful use of speech scale,MUSS)进行言语能力评估.术后行X线耳蜗平片检查明确电极位置及形态,定期随访了解术后相关并发症及佩戴人工耳蜗时间和使用情况.结果 所有患儿术前及开机后1、3、6、12月IT-MAIS或MAIS得分分别为1.67±1.19、6.60±5.12、11.86±5.44、17.41±5.04、22.87±5.46分,术后1、3、6、12月MUSS得分分别为5.01±3.26、8.38±3.58、11.88±3.88、16.58±4.95分,随着植入时间延长得分不断上升(均P<0.05);不同年龄组IT-MAIS或MAIS得分比较:术前A组低于C、D、E组,开机后1、3月A、B组低于E组,开机后6月A组低于C、D、E组,B组低于E组(均为P<0.05);不同年龄组MUSS得分比较:开机后1月B组低于E组,开机后3月A、B、C组低于E组,开机后6月A组低于C、D、E组,B组低于E组,开机后1年A组低于C、D、E组(均为P<0.05).所有患儿在开机后1、3、6、12月MUSS与IT-MAIS或MAIS得分相关系数分别为0.918、0.808、0.881、0.756(均为P<0.05),两者呈正相关.78例患儿术后耳蜗位X线平片均显示电极位置正常,形态良好;2例患儿出现处理器故障,其余CI整体工作状态良好.结论 语前聋患儿国产人工耳蜗植入后1年内,所有患儿的听觉言语能力随时间延长不断提高;小龄组患儿听觉言语得分在术后早期低于大龄患儿;听觉能力在开机后12月时已无差异,但小龄组患儿的言语能力仍低于大龄患儿;听觉整合能力越强,言语使用能力越强;Nurotron-Venus CI安全、效果可靠.     

对脑卒中偏瘫本质的认识及其在针灸治疗中的指导作用

脑卒中偏瘫是中枢性瘫痪的一种，它的本质是运动模式质的改变，因此它的康复过程也就是运动模式质变的过程。本文将偏瘫康复过程分为3期，探讨了各期针灸治疗的目的及原则，并指出传统的肌力练习并不适合于痉挛期，而应以抑制痉挛、促进正常运动模式的发展、促进分离运动的形成为主要原则。     

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.