黄芪发酵粉对环磷酰胺的增效和减毒作用研究

目的:研究黄芪发酵粉(FAP)对肿瘤化疗药物环磷酰胺(Cy)的增效和减毒作用,探索临床上更经济有效的抗癌化疗辅助用药。方法:增效实验采用小鼠移植性肿瘤模型(S180、H22实体瘤和H22腹水瘤),观察FAP与Cy合用对肿瘤抑制率和生命延长率的影响;减毒实验观察FAP对大剂量Cy所致小鼠骨髓抑制、免疫器官萎缩、肾功能损伤等毒性反应的对抗作用。结果:FAP可增强Cy对小鼠S180、H22实体瘤的抑瘤作用;对抗Cy所致小鼠外周血白细胞减少、骨髓有核细胞数减少和脾重减轻等毒性反应,保护肾功能,对肝功能无显著影响。结论:FAP对肿瘤化疗药物Cy有增效和减毒作用。     

黄芪多糖对小鼠化疗中白细胞和骨髓有核细胞减少的影响

目的　探讨黄芪多糖对小鼠在化疗中白细胞和骨髓有核细胞减少的影响。方法　以环磷酰胺引起小鼠白细胞和骨髓有核细胞减少造模。常规计数外周血白细胞数量 ;取股骨测定骨髓有核细胞数量 ;同时采用ID50 法 ,观察黄芪多糖对小鼠环磷酰胺毒性的保护作用。结果　黄芪多糖对小鼠环磷酰胺毒性的小鼠存活率分别提高 2 0 % ,30 % ,5 0 % ,其中以 10 0mg·kg-1黄芪多糖保护作用最为明显 ,对小鼠骨髓有核细胞数和外周血白细胞数量分别提高 86 .8± 10 .4和 72 .1± 14 .2。结论　黄芪多糖对环磷酰胺致小鼠骨髓有核细胞数和外周血白细胞减少及其毒性有明显保护作用     

沙培林对H22小鼠肝癌抑瘤作用的实验研究

目的观察沙培林对如2小鼠肝癌抑瘸作伟及剂量皴应关系。方法H22小鼠肝癌腹水瘤移柏接种后,随机分组,腹腔分别注射沙培林250pg·k^-1、500μg·lkg^-1、750μg·lkg^-1、0．9％氯化纳(NS)、环磷酰胺(CTX)．记录各组平均生存期、计舅生命延长率。结果CTX组生命延长率为29．2％、沙培林各剂量组生命延长率分别为84．6％,92．3％、96．2％,与CTX组比较均有显差异(P<0．05)。结论沙培林对H丝小鼠肝癌有肯定的的瘤作用．且明显优于CTX。沙培林不同剂量组问生命延长率无明显剂量效应关系。     

玉米须多糖对H22荷瘤小鼠的肿瘤抑制作用及其对小鼠免疫功能的影响

目的 考察玉米须多糖对H22肝癌腹水瘤及实体瘤的抑制作用,及其对小鼠免疫功能的影响.方法 建立H22腹水与实体型肿瘤模型,测定荷瘤小鼠的生命延长率、肿瘤抑制率、胸腺指数、脾指数、碳粒廓清率、血清溶血素、白介素-2(IL-2)和肿瘤坏死因子(TNF-α)等指标.结果 玉米须多糖高剂量可改善腹水瘤小鼠的生活质量,生命延长率达到35.82％;且对H22实体瘤小鼠具有显著的抑瘤作用,抑瘤率达到34.78％;玉米须多糖高剂量能明显提高H22荷瘤小鼠廓清指数和吞噬指数,并能显著提高血清中溶血素、IL-2和TNF-α的含量(P＜0.05).结论 玉米须多糖具有显著的抗肿瘤活性,可能是通过调节机体免疫功能来发挥抗肿瘤作用.     

艾迪滴丸对H22荷瘤小鼠化疗的增效减毒作用

目的:观察艾迪滴丸对荷瘤小鼠化疗后的增效减毒作用。方法:建立移植性H22肿瘤小鼠模型,分别观察艾迪滴丸单用以及与阈下量的环磷酰胺(CPA)、5-氟尿嘧啶(5-FU)合用时的抑瘤率;艾迪滴丸与治疗量CPA合用时的体质量、外周血白细胞数和骨髓有核细胞数。结果:艾迪滴丸与CPA、5-FU合用后抑瘤率升高,艾迪滴丸对CPA治疗H22荷瘤小鼠所引起的体质量、外周血白细胞数和骨髓有核细胞数下降有明显的升高作用。结论:艾迪滴丸可增强化疗药的抑瘤效果,减轻化疗不良反应。     

4种重组人粒细胞-巨噬细胞集落刺激因子/白细胞介素-6融合蛋白对环磷酰胺引起的小鼠白细胞减少的恢复作用

目的探讨 4种重组人粒细胞 巨噬细胞集落刺激因子 /白细胞介素 6 (rhGM CSF/IL 6 )融合蛋白在小鼠体内的生物学活性 ,观察它们对环磷酰胺所致Balb/c系小鼠白细胞减少及造血功能损坏的影响。方法给小鼠注射环磷酰胺建立实验模型 ,分别同时注射融合蛋白 7d ,于第 13天摘除眼球采血 ,并进行外周血白细胞计数 ,骨髓有核细胞、单个核细胞记数及CFU GM的测定。结果 4种rhGM CSF/IL 6融合蛋白用药组与生理盐水对照组相比 ,小鼠外周血白细胞数 ,骨髓有核细胞和单个核细胞数以及骨髓CFU GM数均有所增加。结论 4种rhGM CSF /IL 6融合蛋白对环磷酰胺所致小鼠外周血白细胞数减少 ,骨髓有核细胞、单个核细胞数和骨髓CFU GM数减少以及造血功能的损坏具有不同程度的恢复作用。     

牛磺酸对化疗后S_(180)荷瘤小鼠增效减毒作用的研究

目的研究牛磺酸对环磷酰胺化疗后S180荷瘤小鼠的增效减毒作用。方法取健康昆明小鼠50只,将S180肿瘤细胞种植于小鼠右腋窝皮下,建立移植性肿瘤模型。实验分为五组。腹腔注射给药,每日1次,连续8 d。观察不同剂量牛磺酸(Tau)与环磷酰胺(CTX)联合用药的抑瘤率;脾指数和胸腺指数;检测骨髓有核细胞数和外周血白细胞数;MTT法检测NK细胞杀伤活性和脾淋巴细胞增殖活性。结果与模型组比较,CTX组抑瘤率为56.65%,CTX+Tau低、中、高剂量组小鼠的抑瘤率分别为60.10%,72.41%,86.70%,有统计学意义(P<0.01);与CTX组比较,CTX+Tau各剂量组外周血白细胞数,骨髓有核细胞数,脾指数,胸腺指数,NK细胞活性,淋巴细胞增殖活性增高。尤其是CTX+Tau中、高剂量组作用显著(P<0.05)。结论牛磺酸与环磷酰胺联合用药具有增效减毒作用。     

白芍水提物及芍药苷改善环磷酰胺致白细胞减少的对比研究

目的对比观察白芍水提物及芍药苷对环磷酰胺(CTX)致小鼠白细胞减少症的影响。方法给小鼠连续灌胃10d,第6和第7天腹腔注射高剂量CTX造成外周血白细胞减少。比较各给药组和模型组小鼠体质量、外周血白细胞数量、股骨中骨髓有核细胞数及肝、脾、胸腺造血免疫器官脏器系数。结果连续2d腹腔注射CTX 100mg.kg-1,可见小鼠外周血白细胞数、骨髓有核细胞数均显著减少(P<0.01),肝脏、脾脏和胸腺系数均明显降低(P<0.01)。白芍水提物及芍药苷均使小鼠外周血白细胞数、骨髓有核细胞数显著增多,脾脏系数明显升高。用药期间各组小鼠体质量无明显差异。结论白芍水提物及芍药苷对CTX所致小鼠白细胞减少和骨髓细胞减少均有升高作用,可提高CTX减少的小鼠脾脏系数。     

新型八核铜配合物乳剂对小鼠H_(22)腹水瘤的抑制作用

目的探讨新型八核铜配合物乳剂(Nanoporous Octanuclear Cu(Ⅱ),N-Cu)对接种H22腹水瘤小鼠的治疗作用。方法昆明种小鼠90只,腹腔内接种H22腹水瘤细胞株造模,随机分为6组,即生理盐水组、空白乳剂组、顺铂组(DDP 1.0 mg/kg)、低剂量N-Cu组(0.2 mg/mL)、中剂量N-Cu组(0.4 mg/mL)和高剂量N-Cu组(0.8 mg/mL)。H22腹水瘤模型建立24 h后,尾静脉注射0.2 mL/10 g治疗,1次/d,连续给药7 d,观察小鼠的生活状态。称动物体重、腹围及每组采食量,第7天给药后24 h,每组处死5只小鼠,抽取全部腹水,测量腹水体积。取心、肝、脾、肺、肾,肉眼观察,并做病理切片。剩余小鼠观察生存时间,并计算生命延长率。结果与生理盐水组相比,顺铂、不同剂量的N-Cu可显著抑制小鼠H22腹水的生成;各试验用药组较生理盐水组小鼠寿命延长,其中高剂量N-Cu组延长最明显(P<0.05);病理切片结果观察得知:N-Cu各剂量组能显著改善肝环境。结论 N-Cu能抑制小鼠H22腹水的生成,明显延长生存期。     

芦荟抗肿瘤作用研究

目的：研究不同品种芦荟抗肿瘤作用，方法：健康小鼠接种S180肉瘤及H22肝癌腹水瘤，观察其抗肿瘤作用，结果：各品种的芦荟对S180肿瘤均有抑制作用，均能延长荷瘤H22小鼠的生命率。结论：各品种的芦荟均有抗肿瘤作用。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.