腰椎极外侧微创手术的解剖学研究及其临床价值

目的明确国人腰椎侧方解剖层次以及重要组织结构的毗邻关系,评价腰椎极外侧椎体间融合术(XLIF)的可行性和安全性。方法选取10具新鲜尸体标本和2具福尔马林固定的尸体标本,取侧卧位(XLIF体位),在C臂机透视下模拟XLIF手术入路,将克氏针打入L2~5椎间盘中央,沿克氏针方向逐层解剖。测量腰椎侧面正中线腰神经与腰椎前缘交感干之间的距离、腰椎侧面正中线相邻腰节段血管之间的距离以及腰椎各椎体中线位置前后缘距离。结果 XLIF的手术入路相对安全,入路周围未见神经、血管等重要结构。在腰椎侧方,腰节段血管、交感干和腰神经之间存在着一个相对无血管、神经的"安全范围",其大小约为29 mm×30 mm;交感干至腰神经的垂直距离左右两侧差异无统计学意义(P0.05);椎体侧面相邻节段血管的距离左右侧差异无统计学意义(P0.05)。腰椎侧面XLIF微创手术操作的安全范围:L_(2 ~ 3):27 mm×30 mm(修正值0.72 mm×0.65 mm),L_(3 ~ 4):30 mm×32 mm(修正值0.76 mm×0.71 mm),L_(4~5):29 mm×32 mm(修正值0.76 mm×0.69 mm)。结论在XLIF入路周围,腰椎侧方"安全范围"较大,在该范围内进行XLIF手术操作安全性较高。     

Antigenic diversity of the circumsporozoite proteins in the Plasmodium cynomolgi complex

Antigenic diversity was observed in the circumsporozoite (CS) proteins of five of the six Plasmodium cynomolgi isolates (NIH, Mulligan, London, Gombak, Ceylon, RO) that we examined. Monoclonal antibodies were produced against salivary gland sporozoites of three of the isolates. Interaction of these monoclonal antibodies with the sporozoites was isolate specific, the exception being the anti-NIH monoclonals which also reacted with Mulligan strain sporozoites. Inhibition of binding between the different monoclonal antibodies indicated that for each of the NIH, London, and Gombak strains, the homologous monoclonals were recognizing the same or a topographically close immunodominant epitope on the respective CS protein. Also the binding of a polyvalent anti-NIH rhesus serum to the homologous antigen could only be inhibited by anti-NIH monoclonal antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis of sporozoite extracts demonstrated clear differences in the apparent molecular weights of the CS proteins of four of the six isolates. This is the first study which provides evidence of antigenic diversity in the CS proteins of different isolates of a primate plasmodial species.     

菊芋蛋白的提取及其降血糖作用研究

目的 :比较菊芋蛋白两种提取方法的蛋白质提取率,并做菊芋蛋白降血糖研究。方法 :菊芋采用丙酮沉淀法和硫酸铵盐析法提取蛋白质,以蛋白质含量为指标,优选蛋白质提取率高的提取方法,并通过小鼠体内降血糖实验,评价菊芋蛋白的降血糖效果。结果:丙酮沉淀法蛋白提取率为11.30%,硫酸铵盐析法提取率为10.80%;降糖作用研究表明,菊芋蛋白高剂量组降血糖作用明显。结论:丙酮沉淀法提取率高,菊芋蛋白具有降血糖的效果。     

黄连解毒汤自沉淀化学成分及其抗PC12细胞损伤研究

目的探讨黄连解毒汤(HJD)自沉淀制备条件,测定自沉淀主要成分量及自沉淀对PC12细胞损伤模型的保护作用。方法以提取时间和投水量为影响因素,确定自沉淀的制备工艺;采用HPLC法,测定自沉淀中黄芩苷、小檗碱、栀子苷、巴马汀、黄连碱、汉黄芩苷的量;采用CCK-8法评价HJD上清液、自沉淀对CoCl_2损伤的PC12细胞模型作用。结果在10倍量水回流提取30 min的煎煮条件下,干燥后HJD自沉淀质量约占上清液质量的10%,自沉淀中81.28%的成分为酸碱性化合物,其中黄芩苷占42.12%,小檗碱占31.17%,黄连碱占5.89%,汉黄芩苷占1.50%,巴马汀占0.60%,未检测到中性成分栀子苷。上清液、自沉淀对CoCl_2损伤的PC12细胞的EC50值分别28.25、19.58μg/m L。结论自沉淀制备工艺操作简单,重复性好,通过成分分析,得出自沉淀的形成机制以酸碱络合为主的假想;与上清液相比,自沉淀表现出较好的神经保护活性,为HJD的二次开发提供参考。     

气象学视域下的南宋《局方》续添方剂考述

[目的]探讨气象学视域下南宋两次《太平惠民和剂局方》(以下简称《局方》)续添与气候变化的联动关系。[方法]通过数据分析,找出南宋续添方剂与《局方》的整体差异;通过史料考证,归纳两宋尤其是南宋气候变动的特点;基于以上文献及数据,探讨南宋《局方》续添方剂与气候变动的相关性。[结果]绍兴续添方、续添诸局经验秘方体现出与《局方》整体的显著差异,也表现出与气候变动的显著相关性。在时间上,两次续添分别发生在两次重大气候变动的中后期。在方剂选择上,绍兴续添方体现为对寒湿气候的响应,以寒湿为病因、病机、主治的续添方剂最为突出,续添诸局经验秘方体现为对大量自然灾害及沙尘气候的响应,以虚证为病因、病机、主治的续添方剂最为典型。[结论]绍兴续添方和续添诸局经验秘方均受到气候变动的显著影响。从气候变化的角度阐述《局方》续添方剂的特点,丰富了医学史理论。     

Fast transmission of alterations in plasma phosphatidylcholine/sphingomyelin ratio and lyso phosphatidylcholine levels into changes of red blood cell membrane phospholipid composition after low density lipoprotein apheresis

Abstract. In order to evaluate whether changes in plasma phospholipid composition are rapidly transmitted to the red blood cell membrane (RBCM) under in vivo conditions, the levels of major phospholipids in plasma, low density and high density lipoproteins (LDL and HDL) as well as in RBCM were determined before (pre), directly after (post) and 2 days after (48 h post) LDL apheresis in six patients with severe hypercholesterolaemia. LDL apheresis induced a 30–70% decrease in plasma and LDL cholesterol and total phospholipid levels within 2–3 h. Concomitantly, the percentages of plasma phosphatidylcholine (PC) and the PC/sphingomyelin (SM) ratio were increased compared to initial values. The percentage of plasma lyso PC (LPC) determined before apheresis in the patients was 30% lower with respect to the mean level of LPC in a normolipidaemic control. For LPC of LDL no differences were observed between normolipidaemia and hypercholesterolaemia. LDL apheresis induced a rise by about one third in the percentage of plasma LPC. At 48 h post, plasma LPC levels reapproached pre-apher-esis levels, while the percentages of PC and the PC/SM ratio remained elevated. The pattern of changes induced by apheresis in plasma PC, SM and LPC levels was mimicked by changes in RBCM phospholipids. Strong positive relationships were noted for PC, SM and PC/SM as determined at pre, post and 48 h post between plasma and RBCM. In summary, changes in plasma PC, LPC, and PC/SM ratios as induced by LDL apheresis are rapidly transmitted to the RBCM under in vivo conditions, most probably as a result of phospholipid transfer between both compartments. In addition, the percentages of LPC in plasma and LDL particles of patients with severe hypercholesterolaemia are certainly below the levels of LPC reported to mediate biological effects of in vitro oxidized LDL.     

Continuous production of aqueous suspensions of ultra-fine particles of curcumin using ultrasonically driven mixing device

Abstract

Developing drug formulations for poorly water-soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives, and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time, and solid–liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process.     

Process Development and Robust Control of Physical Attributes of an Amorphous Drug Substance

Control of physical attributes of amorphous active pharmaceutical ingredients (APIs) can be challenging due to processability issues, their wide variation during processing and the requirement to control them to specific ranges. In this article, we report our efforts to develop a robust isolation process for boceprevir, which delivers specific surface areas between 3.0 and 9.4 m²/g. We developed mechanistic process understanding by utilizing a new method to measure glass transition temperature of API suspensions. Boceprevir processability and surface area are determined by the interplay between the suspension operating conditions and glass transition temperature. Processing time and thermal history also influence API surface area evolution, rendering a dynamic nature to it. A control strategy was developed consisting of 2 elements: a continuous tee mixer precipitation process, which delivers API in the 40-60 m²/g range and 1 of 2 annealing step variants. In the first, surface area was controlled in 4 batches to 6.7-7.5 m²/g by equilibrating the API suspension above its glass transition temperature and a subsequent vacuum distillation. The second annealing variant controlled surface area to 4.5-6.5 m²/g for over 70 commercial batches through a dynamic vacuum distillation step with prescribed temperature and % batch volume distilled profiles versus time.     

Addition of Cationic Surfactants to Lipid-Based Formulations of Poorly Water-Soluble Acidic Drugs Alters the Phase Distribution and the Solid-State Form of the Precipitate Upon In Vitro Lipolysis

It has been previously shown that the interaction of some weakly basic drugs with oppositely charged fatty acids during digestion can influence the solid-state form of the drug if it precipitates. The present study hypothesized the opposite effect for weakly acidic drugs. Tolfenamic acid (TA) and an oppositely charged cationic surfactant, didodecyldimethylammonium bromide (DDAB) were combined in a model medium chain lipid formulation. The phase distribution upon in vitro lipolysis was determined using HPLC and the solid-state form of precipitated TA was determined using X-ray diffraction and crossed polarized light microscopy. TA precipitated in a different polymorphic crystalline form to the starting reference material in the absence of DDAB but precipitated in an amorphous form when DDAB was included in the same formulation. The solubility of TA upon dispersion and digestion of the formulation was considerably higher in the presence of DDAB. The findings point to ionic interactions between TA and DDAB as the reason for the improved drug solubility throughout digestion, and precipitation of drug in an amorphous salt form, analogous to what has been observed in the past for some poorly water-soluble weakly basic drugs with anionic co-formers.     

红芪不同提取物对环磷酰胺所致免疫低下小鼠的影响及相关成分含量研究

目的对比研究红芪不同提取物对环磷酰胺(CTX)所致免疫低下小鼠的影响及相关化学成分含量。方法按照体重将昆明种小鼠随机分为空白组、模型组、对照组、醇提物组、水提物组、醇沉物组、残留物组。用CTX 40 mg·kg^-1造成免疫低下模型。对照组灌胃参芪颗粒5 g·kg^-1,其他各组灌胃相应受试样品2 g·kg^-1,正常组和模型组灌胃等量0.9%Na Cl,每天给药1次,连续15 d。称重计算小鼠脏器指数,腹腔注射5%鸡红细胞悬液(CRBC)测定腹腔巨噬细胞吞噬百分率及吞噬指数,用50%二硝基氯苯(DNCB)丙酮溶液致迟发型超敏反应测定OD值,用5%CRBC致敏测定血清溶血素OD值,尾静脉注射印度墨汁测定网状内皮系统吞噬指数及吞噬系数。用UV法测定多糖、总皂苷含量。结果模型组各指标与正常组比较,差异均有统计学意义(均P<0.01)。给药后,正常组、模型组与醇提物组、水提物组、醇沉物组、残留物组的胸腺指数(g·kg^-1)分别为2.55±0.88,1.04±0.74,1.24±0.79,1.81±0.62,1.97±0.83,1.09±0.75,水提物组、醇沉物组与模型组比较,差异均有统计学意义(均P<0.05);水提物组、醇沉物组与残留物组比较,差异均有统计学意义(P<0.05)。这6组的腹腔巨噬细胞吞噬百分率(%)分别为48.58±5.51,28.54±3.15,35.28±6.03,36.99±6.78,39.89±8.33,27.91±8.02,醇提物组、水提物组、醇沉物组的吞噬百分率与模型组比较,差异均有统计学意义(P<0.05或P<0.01);水提物组、醇沉物组与残留物组比较,差异均有统计学意义(P<0.05或P<0.01)。这6组的迟发型超敏反应OD值分别为0.53±0.16,0.23±0.09,0.30±0.10,0.37±0.10,0.36±0.11,0.28±0.14,水提物组、醇沉物组与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。各提取物中多糖和总皂苷含量:醇提物(6.35%;6.57%),水提物(22.64%;7.68%),醇沉物(42.15%;1.86%),残留物(4.33%;5.37%)。结论红芪水提物和醇沉物均能对抗CTX的免疫抑制作用,有一定的增强体液免疫和细胞免疫作用,可增强机体的非特异性免疫和特异性细胞免疫功能。推测多糖是其对抗CTX免疫抑制作用的主要活性部位。