Degradation of Paclitaxel and Related Compounds in Aqueous Solutions III: Degradation Under Acidic pH Conditions and Overall Kinetics

Paclitaxel and related taxanes are complex molecules with numerous hydrolysable ester groups, possible epimerization at the 7‐position, and possessing a strained oxetane ring, a possible site for acid‐catalyzed cleavage. Presented here is the stability of paclitaxel, 10‐deacetylbaccatin III, baccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester in aqueous solution over a pH range of 1–5 at various temperatures. Analysis of various samples was by HPLC–UV and LC–MS. Baccatin III, 10‐deacetylbaccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester were found to undergo acid catalysis since pH‐rate profiles all followed a first‐order dependency in hydrogen ion concentration. No evidence of any epimerization was noted at acidic pH values. Baccatin III and 10‐deacetylbaccatin III showed similar degradation rates with possible products being possible dehydration around the 13‐hydroxy group and cleavage of the oxetane ring. Cleavage of the 10‐acetyl group of baccatin III was a minor initial pathway. N‐Benzoyl‐3‐phenylisoserine ethyl ester degraded significantly slower than both 10‐deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate between that of N‐benzoyl‐3‐phenylisoserine ethyl ester and 10‐deacetylbaccatin III. The pH of maximum stability for all compounds appeared to be around pH 4. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1288–1298, 2010     

新生儿脐炎85例脐部分泌物细菌学分析

目的：了解新生儿脐部感染细菌学状况，为临床提供预防及治疗参考。方法：调查我院1997年1月－2002年6月收治的有完善细菌学资料的新生儿脐炎85例，对所获得的98例致病菌的种类及药敏状况进行分析。结果：社会获得性感染主要致病菌为G^ 球菌（70．5％），金黄色葡萄球菌占比例较高。医院感染主要致病菌为C^-杆菌（51．4％），以大肠埃希菌占比例较高。两类感染所分离的细菌均具有多重耐药性，但对氨基糖苷类及喹诺酮类耐药率较低，其次是第三代头孢菌素类抗生素。结论：临床对新生儿脐部感染，特别是有严重感染中毒症状时，应首先考虑使用第三代头孢菌素类抗生素。     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Ischemia and reperfusion reduce the endogenous basic fibroblast growth factor in rat skeletal muscles: an immunohistochemical study.

Polyclonal antibodies directed against human recombinant basic fibroblast growth factor were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. According to the intensity of the stain, three main classes of fibers could be identified: the strongly, moderately, and weakly stained fibers. Basic fibroblast growth factor immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, which includes the heparin-containing basal lamina, and also in the capillary basal membrane of both normal and wounded muscles; however, the signal intensity was much stronger in normal muscles. The distribution of basic fibroblast growth factor in wounded muscles became markedly heterogeneous and sparse. After 4 hours of ischemia, about 40% of skeletal muscle fibers lost their basic fibroblast growth factor immuno-reactivity. Muscles which underwent 4 hours of ischemia and 24 hours of reperfusion had only a diminished basic fibroblast growth factor immunoreactivity. The pathologic results supported the concept of destroyed cell connection and fiber necrosis in ischemic and reperfused muscles. Potential mechanisms involved in this reduced concentration of basic fibroblast growth factor in wounded muscles may include oxygen free radical activation, a generalized effect of the inflammatory response, and reduced secretion of endogenous basic fibroblast growth factor. These results are only partially compatible with the established mitogenic role of this growth factor and suggest that a reduction of endogenous fibroblast growth factor may partly contribute to a delay in wound healing.     

地榆鞣质抗肝癌细胞SMMC—7721的MTT及FCM分析

探讨中药成分地榆鞣质的抗癌活性，并试图建立一种筛选抗癌药物的方法，方法：运用ＭＴＴ法测定ＳＴＭ及ＳＴＬ对体外培养人肝癌ＳＭＭＣ－７７２１细胞的杀伤率并通过流式细胞仪分析细胞分裂周期各时象ＤＮＡ变化。结果；ＳＴＭ与ＳＴＬ均有明显抗癌活性，与阴性对照组相比有显著差异，并具有剂量效应关系，ＳＴＭ，ＳＴＬ与ＭＭＣ联合用药抗癌活性增强，与单独用药组相比差异显著；     

米非司酮配伍米索前列醇终止早孕118例临床观察

就米非司酮配伍采米前列醇序贯用药终止７周内早孕１１８例进行临床观察，发现完全流产率９２．３７％，不全流产率５．９３％，持续妊娠率１．６９％。临床证明该方法方便、安全有效、副作用极小，但个别孕妇产生不全流产，引起出血过多及出血时间延长。不全流产率有随孕妇年龄、孕龄、孕次增加而增加的趋势。     

Protective effect of Re-LPS antiserum on experimental multiple system organ failure.

This study examines the possible beneficial effect of Re-LPS (F515) antiserum on experimental multiple system organ failure (MSOF) in rabbits. The results showed that the plasma LPS level was significantly decreased, and it took a shorter period to clear up LPS in experimental than in control rabbits after receiving Re-LPS antiserum. Pretreatment with antiserum can markedly improve the function of the liver, lungs, kidneys, blood and gastrointestinal tract. The MSOF incidence in the group of rabbits receiving immune sera was only 11.2% and the survival rate was raised by about 40.0%. The results suggest that early passive immunotherapy may neutralize gut-derived endotoxin, inhibit endotoxin-induced mediators release and prevent development of severe complications due to sepsis. It is therefore postulated that LPS core antiserum may provide a prophylactic effect on the development of experimental MSOF.

     

杀菌性通透性增强蛋白对失血性休克的保护作用及其机理

分别在失血和复苏开始即刻ｉｖ杀菌性／通透性增强蛋白（ＢＰＩ）１．５和３．５ｍｇｋｇ－１，观察ＢＰＩ对大鼠失血性休克转归的影响．结果显示，ＢＰＩ治疗能明显改善失血性休克大鼠肝肾功能，提高休克动物存活率（ＢＰＩ组８１％ｖｓ休克对照组４４％，Ｐ＜０．０５），ＢＰＩ组大鼠复苏后与休克前的血浆内毒素（０．２０±０．０４ｖｓ０．２４±０．０５ｋＵＬ－１）水平无明显变化，血浆肿瘤坏死因子α和白介素６水平较休克前明显升高，但均显著低于休克对照组．提示ＢＰＩ对失血性休克大鼠具有一定的保护作用，其机理可能与ＢＰＩ拮抗休克时内源性内毒素活性，抑制细胞因子反应有关．     

锌离子对大鼠海马突触体Ca^2＋—Mg^2＋ATP酶活性及蛋白合成的影响

行为实验己经证明，锌过多或缺锌均可影响脑功能。锌作为体内重要的微量元素，影响多种酶的活性及蛋白质和核酸的台成。本实验通过体外分离大鼠脑海马突触体，观察不同浓度锌离子对Ca2 －Mg2 ATP酶的活性和3H－Leu掺入突触蛋白合成的影响．结果表明：1．锌离子浓度在25μmol／L时增加该酶的活性（＜0．01），并促进3H－Leur掺入蛋白质的合成（＜0．05）。2．锌离子在50,100，200μmol／L的较高浓度时对Co2 －M2 ATP酶的活性有显著的抑制作用（分别为：P＜0.05．P＜0．01，P＜0.01），仅200μmol／L对3H—Leu掺入突触蛋白合成有抑制作用。本研究提示：适量的锌对突触体功能的维持是必要的，但剂量过高则起相反作用。     

颅颌面形态有限元分析系统的初步建立

初步建立一个用于颅颌面形态变化研究的有限元分析系统。方法：程序用ＢｏｒｌａｎｄＣ语言编写，对临床常用的Ｘ线头颅定位片进行分析，将呆分析的头颅定位片描在硫酸纸上，用图形数值化仪把节点输入计算机。根据有限元分析法的原理，将头颅定位片上的颅颌面结构份割许多三角形单元，用应变张量来描述颅颌面形态变化。