静态直立时足位对眩晕患者姿势平衡的影响

目的：分析不同足位对眩晕患者静态直立时的姿势平衡影响。探讨足位在平衡控制和姿势描记中的作用。方法：眩晕组79例患者和正常组92例健康者进行如下静态直立试验：①标准Romberg试验，双足并拢站立；②双脚分开平行直立试验；③强化Romberg试验（踵趾位站立）；④单足直立试验。每种测试条件下分别睁眼和闭眼站立，用秒表记录①-④试验中维持平衡的时间，同时用SPG记录①、②条件下的人体足底压力中心的晃动速度（sway velocitv，SV）。结果：①维持平衡时间：眩晕组采取踵趾位和单足站立时，维持平衡时间较正常组降低．差异均有极显著性意义（P〈0．001）；②SV：采用标准Romberg位和双脚分开站立，眩晕组和正常组相比，睁眼时两组SV差异无显著性意义（P〉0．05）。而闭眼时，两组间差异均有显著性意义（P〈0．001）；③对于眩晕组和正常组，无论睁眼或闭眼，采用双脚分开站立时，SV较标准Romberg位时降低。差异有极显著性意义（P〈0．001）：④除眩晕组闭眼踵趾位下计时平衡试验结果与其睁眼时标准Romberg足位下的SV呈负相关性外（r=-0．244，P=-0．03），其他计时平衡测试结果与各足位下的SV均未发现有相关性。结论：静态直立时不同足位可影响人体平衡控制能力，踵趾位和单足直立测试是对姿势描记的补充．可结合应用于临床评价眩晕患者的平衡功能。     

Attaining in vivo selectivity of positive modulation of α3βγ2 GABAA receptors in rats: A hard task!

It is unclear whether GABA_A receptors (GABA_ARs) that contain the α3-subunit are substantially involved in the anxiolytic effects of benzodiazepines (BDZs). In the present study, we tested YT-III-31, a newer BDZ ligand with functional preference for α3βγ2 GABA_ARs, in two paradigms of unconditioned anxiety, the open field and elevated plus maze in rats. The effective dose of YT-III-31 (2?mg/kg) displayed a clear anxiolytic-like profile, unhampered by sedative action, in both tests. At a higher dose (10?mg/kg), YT-III-31 induced ataxia in the rotarod and sedation in spontaneous locomotor activity test. The latter effect was preventable by flumazenil and βCCt, the non-selective and α1βγ2 GABA_AR affinity-selective antagonist, respectively, demonstrating that sedative properties of YT-III-31, when attained, are mediated by the α1γ2 site. To elucidate the receptor substrate of subtle behavioral differences between YT-III-31 and diazepam, we approximated in vivo receptor potentiation for both ligands, based on estimated unbound concentrations in rat brains. Far different from diazepam, YT-III-31 has significantly lower affinity for the α1γ2 over other BDZ-sensitive sites, and at lower doses (1–2?mg/kg) was devoid of potentiation at α1βγ2 GABA_ARs. The approximation approach revealed a modest selectivity of YT-III-31 for α3γ2- in comparison to α2γ2 and α5γ2 binding sites, suggesting that its anxiolytic-like activity may not necessarily or predominantly reflect potentiation at α3βγ2 GABA_ARs. Nonetheless, as the anxiolytic effects are achievable at a dose devoid of any sedative potential, and having favorable safety (cytotoxicity) and metabolic stability profile, YT-III-31 represents a valuable candidate for further translational research.     

更昔洛韦氯化钠注射液与聚丙烯输液瓶的相容性评价

目的 探讨聚丙烯输液瓶的安全性及其与更昔洛韦氯化钠注射液的相容性。方法 建立抗氧剂、抗酸剂的检测方法,通过提取试验、迁移试验和吸附试验研究注射液与包装材料的相互作用,根据添加剂的毒理学研究资料评价其相容性。结果 抗氧剂及其氧化物和降解物采用HPLC测定,报告限为0.098~0.98 μg·mL^-1;抗酸剂中的镁、铝元素采用AAS测定,报告限为0.025~0.1 μg·mL^-1。各添加剂的分析评价阈值为0.83~117 μg·mL^-1,均高于各自报告限。提取和迁移试验中注射液中未检出添加剂成分,也未见API被明显吸附。结论 聚丙烯输液瓶浸出物含量低于每日允许最大暴露量,对更昔洛韦氯化钠注射液没有吸附作用,相容性好。     

Determination of Interaction Parameters for Reversibly Self-Associating Antibodies: A Comparative Analysis

Monoclonal antibodies (mAbs) represent a major class of biotherapeutics and are the fastest growing category of biologic drugs on the market. However, mAb development and formulation are often impeded by reversible self-association (RSA), defined as the dynamic exchange of monomers with native-state oligomers. Here, we present a comparative analysis of the self-association properties for 5 IgG mAbs, under matched conditions and using orthogonal methods. Concentration-dependent dynamic light scattering and sedimentation velocity studies revealed that the majority of mAbs examined exhibited weak to moderate RSA. However, because these studies were carried out at mAb concentrations in the mg/mL range, we also observed significant nonideality. Noting that nonideality frequently masks RSA and vice versa, we conducted direct boundary fitting of the sedimentation velocity data to determine stoichiometric binding models, interaction affinities, and nonideality terms for each mAb. These analyses revealed equilibrium constants from micromolar to millimolar and stoichiometric models from monomer-dimer to isodesmic. Moreover, even for those mAbs described by identical models, we observed distinct kinetics of self-association. The accuracy of the models and their corresponding equilibrium constants were addressed using sedimentation equilibrium and simulations. Overall, these results serve as the starting point for the comparative dissection of RSA mechanisms in therapeutic mAbs.     

Modeling of a Hybrid Langmuir Adsorption Isotherm for Describing Interactions Between Drug Molecules and Silica Surfaces

The interaction between disulfiram (Antabus^®) and silica was studied experimentally by adsorption from apolar solvent onto highly porous silica material (Santa Barbara amorphous material-3) with large surface area. The adsorption isotherm was fitted to the Langmuir model by accounting 2 different affinities contributing to the overall behavior, which were attributed to 2 different types of silanol groups (i.e., geminal and vicinal) present on amorphous silica surfaces. This assumption was supported by theoretical calculations. In addition, the model could describe the adsorption of ibuprofen to the carrier material, indicating that the model bears big potential for describing the interactions between silica surfaces and drug molecules.     

应用大孔吸附树脂分离纯化葶苈子总黄酮的研究

目的考察6种大孔树脂对葶苈子总黄酮成分的分离纯化性能,确定最佳工艺条件。方法以总黄酮吸附量、洗脱率、洗脱物总黄酮含量为指标,采用紫外-可见分光光度法进行含量测定。结果NKA-Ⅱ型树脂对葶苈子总黄酮具有较好的纯化分离能力,其最佳工艺条件为:葶苈子提取物浓度4g/mL(生药量),最大吸附量12.92mg/g,装柱径高比1∶12,吸附流速3mL/min,洗脱剂80%乙醇,洗脱量5倍柱体积,洗脱流速3mL/min。结论NKA-Ⅱ型树脂纯化分离葶苈子总黄酮的最佳工艺稳定高效,可推广用于生产。     

腰椎滑脱症融合术后脊柱矢状面平衡改变与疗效的关系

目的探讨经椎间孔腰椎椎间融合术(TLIF)单节段及双节段固定对退行性腰椎滑脱症患者脊柱矢状面参数的影响及其与疗效的关系。方法收集南京医科大学第一附属医院44例(Ⅰ度32例,Ⅱ度12例)经TLIF治疗的退行性腰椎滑脱症患者的临床及影像学资料,根据手术固定节段分为单节段组(29例)和双节段组(15例)。分析比较术前、术后全脊柱侧位X线片的矢状面参数脊柱骶骨角(SSA)、T_1骨盆角(TPA)、腰椎前凸(LL)、骨盆投射(PI)、骨盆倾斜(PT)及骶骨倾斜(SS),以及疼痛视觉模拟量表(VAS)评分、日本骨科学会(JOA)评分及Oswestry功能障碍指数(ODI)。结果全部病例均获得随访,随访时间3~10个月,平均6个月。全组患者术后SSA、TPA、LL、SS均较术前增大,PT较术前减小,差异均有统计学意义(P0.05),VAS评分、JOA评分和ODI均较术前改善,差异均有统计学意义(P0.05)。单节段组手术前后LL差值、ODI差值与双节段组比较差异有统计学意义(P0.05),且2组手术前后LL差值与ODI差值均相关。SSA差值在双节段组与VAS评分差值相关,在单节段组二者无相关性。结论Ⅰ度或Ⅱ度退行性腰椎滑脱症患者通过TLIF治疗可改善脊柱矢状面参数,且单节段固定更有利于术后脊柱矢状面参数的改善。     

配对血浆分离吸附联合血液滤过治疗多器官功能障碍综合征的实验及临床研究

目的探讨配对血浆分离吸附法（CPFA）联合连续性静-静脉血液滤过（CVVH）治疗多器官功能障碍综合征（MODS）伴急性肝功能衰竭（ALF）患者的临床疗效和安全性。方法应用CPFA＋CVVH技术对重症加强治疗病房（ICU）中11例MODS伴ALF患者进行38例次治疗，比较患者治疗前后的平均动脉压（MAP）、氧合指数（Pa02／FiO2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、IL-8、肝功能、肾功能、全身炎症反应综合征（SIRS）评分、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分及临床症状改善程度，同时观察治疗的不良反应，并进行治疗安全性评价。结果患者治疗后尿量较治疗前增多，黄疽减轻，发热、乏力、腹胀、食欲明显改善，精神好转，意识转清。治疗后MAP较治疗前上升了12mmHg（1mmHg=0．133kPa），PaO2／FiO2上升了40mmHg（P均＜0．05）；TNF-α、IL-1β、IL-6、IL-8均较治疗前明显降低（P均＜0．05），血清总胆红素、直接胆红素、血氨、血尿素氮、肌酐均明显下降（P均＜20．05）；SIRS、APACHEⅡ评分均较治疗前有不同程度的下降（P均＜0．05）。11例患者存活5例，存活率为45．5％；未发生出血、休克、过敏等并发症，患者耐受好。结论CPFA联合CVVH能有效清除炎症介质，改善MODS伴ALF患者的预后，且无明显不良反应。     

腰椎融合联合Coflex动态固定手术对腰椎矢状面平衡的影响及其与临床疗效相关性分析

目的 探讨腰椎融合联合Coflex动态固定手术（topping-off）对腰椎矢状面平衡的影响,并分析其与临床疗效的相关性.方法 2008年8月-2012年8月,31例腰椎退变性疾病患者接受腰椎融合联合Coflex动态固定手术,在术前及末次随访时对所有患者进行疼痛视觉模拟量表（visual analogue scale,VAS）评分和Oswestry功能障碍指数（Oswestry disability index,ODI）,同时测量腰椎前凸角和骶骨倾斜角,进行统计学分析.结果 所有患者均获得6个月以上随访,末次随访时VAS评分和ODI均获得显著改善（P＜0.001）.末次随访时,腰椎前凸角与术前相比无明显变化（P＞0.05）,而骶骨倾斜角则显著增加（P＜0.05）.根据随访时间将所有患者分为3年以内组（A组）和3年以上组（B组）,与术前相比,末次随访时A组患者腰椎前凸角呈轻度增加趋势,但差异无统计学意义（P＞0.05）,骶骨倾斜角无显著变化（P＞0.05）;与术前相比,末次随访时B组患者的腰椎前凸角呈增加趋势,但差异无统计学意义（P＞0.05）,骶骨倾斜角则显著增加（P＜0.05）.各临床疗效评分与末次随访时腰椎前凸角和骶骨倾斜角测量结果无明显相关性.结论 腰椎融合联合Coflex动态固定手术治疗腰椎退变性疾病的近中期疗效较为满意,手术对腰椎矢状面平衡有一定保护作用.未发现术后临床疗效与矢状面平衡指标存在明显相关性.     

调节不同pH值的免疫吸附洗脱液的细菌内毒素测定

目的选择不同浓度的氢氧化钠碱性调节剂或直接稀释法对免疫吸附洗脱液的pH值进行调节比较,建立免疫吸附洗脱液的细菌内毒素检查方法。方法根据《中国药典》2010年版第二部附录收载的细菌内毒素检查方法,采用鲎试剂法对免疫吸附洗脱液进行干扰试验。结果稀释32倍的免疫吸附洗脱液对细菌内毒素与鲎试剂的反应无干扰,选择灵敏度为0.015EU·mL-1的鲎试剂进行细菌内毒素检查。结论选择直接稀释法调节供试品的pH值更优于低浓度氢氧化钠碱性调节剂调节供试品的pH值对其进行细菌内毒素的检查。