银杏叶聚戊烯醇抗癌作用的初步研究

目的 :研究银杏叶 (FoliumGinkgo)提取物—聚戊烯醇 (PolyprenolsGP 1 )的抗肿瘤作用。方法 :采用动物抗移植性肿瘤实验方法。结果 :1 0 0mg/kg的聚戊烯醇对移植性肝癌Heps和肉瘤S1 80 的实验抑制率分别为 49 1 3 %和 46 53% ,40 0mg/kg的聚戊烯醇对艾氏癌EC抑制率为 49 65 % (P <0 0 1 )。银杏叶聚戊烯醇对艾氏腹水癌EAC小鼠无明显延长寿命作用。结论 :银杏叶聚戊烯醇有良好的抗肿瘤作用 ,应进行深入研究     

2-(E)-取代苯亚甲基环戊酮及其Mannich碱盐酸盐类化合物的合成和抗炎、抗癌活性研究

本文设计,合成了2-(E)-取代苯亚甲基环戊酮(Ⅰ)类化合物18个及其Mannich碱盐酸盐(Ⅱ)类化合物11个,其中22个为新化合物。初步药理结果显示:对于角叉菜胶诱发的大鼠足趾水肿,Ⅰ₄,Ⅰ₁₂及Ⅰ₁₃口服有较显著的抑制作用,水溶性Ⅱ类化合物皮下注射有极强的抑制作用,其中Ⅱ₃于50,25和12.5 mg/kg剂量下抑制率分别为95.8%,70.3%和44.2%,它与布洛芬效力(25 mg/bg抑制率72.9%)相当.Ⅱ类化合物体外对L1210细胞及体内对荷艾氏腹水癌小鼠均有一定抗癌活性。     

银杏叶聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的抗癌作用

目的研究聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的药效作用。方法从银杏叶中分离纯化聚戊烯醇 ,分别与氟脲嘧啶 (5 Fu)、环磷酰胺 (CTX)和顺铂 (PDD)联合应用 ,对移植性Heps和EC荷瘤小鼠进行抑瘤实验 ,并与 5 Fu、CTX和PDD单独用药比较。结果聚戊烯醇分别与CTX、PDD合用 ,对肝癌Heps的抑瘤率分别从4 2 .2 5 %、4 5 .0 4 %提高到 5 6 .4 9%、5 4 .96 % ;聚戊烯醇分别联合CTX、5 Fu用药 ,对艾氏腹水瘤EC的抑瘤率分别从37.6 4 %、39.89%提高到 6 2 .92 %、5 3.37%。结论聚戊烯醇对抗肿瘤药具有明显的辅助治疗和减毒增效的作用     

抗癌新药-乙双吗啉(AT-1727)的药理研究

乙双吗啉(AT-1727)是我国合成的一种抗癌新药。它是一种双内酰亚胺化合物,实验证明,乙双吗啉对小鼠肉瘤S₃₇、S₁₈₀有显著抗肿瘤作用,对ECS,HCS,脑瘤B₂₂及L₆₁₅等移植性肿瘤亦有明显抗肿瘤作用。它对S₃₇的50%抑制剂量(ID₅₀)为1.88 mg/kg(ip)及6.61 mg/kg(po)。其抗肿瘤作用与给药方案有一定关系。乙双吗啉对小白鼠毒性LD₅₀为372.8±27.mg/kg(ip)及243.8±26.1 mg/kg(po)。因此,乙双吗啉腹腔注射及口服时,对S₃₇的化疗指数分别为47.5及36.9。给健康犬肌肉注射乙双吗啉25及50 mg/kg/天,连用10天,除出现食量减少,白细胞轻度下降外,对红细胞,血小板、肝、肾功能均无明显影响。乙双吗啉对以溶血素反应为指标的体液免疫有抑制作用;对以移植物抗宿主反应为指标的细胞免疫则无抑制作用。     

中药大黄的综合研究——Ⅻ.蒽醌衍生物对艾氏腹水癌细胞呼吸和酵解的影响

本实验观察大黄蒽醌衍生物对艾氏腹水癌细胞呼吸和酵解的影响。实验结果表明:(1)大黄素对艾氏腹水癌细胞呼吸有较强的抑制作用,50%抑制的浓度为20μg/ml,至于大黄酸则有中等程度的抑制作用,而芦荟大黄素和大黄酚只有轻度的抑制作用。(2)大黄素对艾氏腹水癌细胞对某些氨基酸和糖代谢中间产物的氧化和脱氢也有很强的抑制作用,例如大黄素50μg/ml对乳酸的氧化和脱氢的抑制率分别为87%和91%。(3)大黄酸对艾氏腹水癌细胞的酵解也有明显的抑制作用,25μg/ml的抑制率为60%,而大黄素对酵解则反而有刺激作用。(4)大黄素(25和50μg/ml)和大黄酸(25μg/ml)对宿主正常组织,如肝和肾等匀浆呼吸几乎无抑制作用,但大黄酸50μg/ml对正常组织,尤其是脑组织匀浆呼吸有一定的抑制作用。     

长柱重楼总皂苷的抗肿瘤活性及急性毒性作用研究

目的 研究长柱重楼总皂苷（PCT3）的体内外抗肿瘤活性及ig一次性给药的急性毒性。方法 采用改良MTT法检测PCT3对人结直肠癌（HCT-116）细胞和人胃癌（SGC-7901）细胞增殖的影响,计算半数抑制浓度（IC₅₀）。ig一次性给予小鼠1.646、2.352、3.360、4.800 g/kg PCT3进行急性毒性测试。建立小鼠皮下肝癌（H22）模型,分别ip顺铂2 mg/kg（阳性对照）、生理盐水（阴性对照）;ig给予0.5% CMC-Na（溶剂对照）、30、90、270 mg/kg PCT3,连续给药9 d,检测小鼠肿瘤、体质量抑制率,肝、脾、肾、胸腺系数。结果 与阴性对照组比较,PCT3对HCT-116和SGC-7901细胞增殖有明显的抑制作用（P<0.05、0.01）,IC₅₀分别为7.6、5.9 μg/mL。大剂量PCT3可致动物腹泻及活动抑制,半数致死量（LD₅₀）为1.985 5 mg/kg。与溶剂对照组比较,PCT3对小鼠体质量无显著影响;270 mg/kg PCT3对H22肿瘤发挥显著抑制作用（P<0.05）,抑制率为26.8%;对各脏器系数均无显著影响;与阴性对照组比较,顺铂显著抑制肿瘤和体质量的增长（P<0.01）,抑制率分别达81.4%和37.4%;对肝脏、脾脏、胸腺系数均发挥显著抑制作用（P<0.05、0.01）。结论 顺铂抑瘤率明显高于PCT3,但其显著抑制小鼠的体质量和肝脏、脾脏、胸腺系数,PCT3在体内外具有一定的抗肿瘤活性,且毒性较低,其活性及作用机制有待进一步研究。     

葛根对β-肾上腺素能受体阻滞作用的研究

本文报告了葛根浸膏具有较为广泛而显著的β-受体阻滞效应。且对β₁-受体的作用强于β₂-受体。相当于0.5～5mg/ml或750mg/kg的葛根能分别对抗异丙肾上腺素0.17～1.7μg/ml或10μg/kg诱发的离体或在体心脏的兴奋作用。此外,相当于750mg/kg的葛根除能阻滞10μg/kg异丙肾上腺素及肾上腺素舒血管(β-受体效应)所致的降压作用外,尚能降低正常心率(平均下降43.7%)及血压(平均下降40±6mmHg)的作用,这些结果为葛根用来缓解心绞痛,治疗快速型心律失常及高血压等提供了根据。将葛根(750mg/kg)与心得宁(0.1mg/kg)抗异丙肾上腺素(10μg/kg)所致的β-受体效应加以比较,表明两者作用大体相似,减慢心率的作用心得宁似乎稍强于葛根。降压作用葛根略优于心得宁,且葛根无明显的抑制心脏的作用。根据上述事实,可以认为葛根是一种有效的β-受体阻滞剂。     

氟哌啶醇对大鼠离体海马脑片和原代神经元缺糖/缺氧和N-甲基-D-天冬氨酸损伤的保护作用

目的观察氟哌啶醇对大鼠离体海马脑片和原代神经元的缺糖/缺氧(OGD)和N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)损伤的潜在保护作用及其机制。方法海马脑片OGD以无葡萄糖的人工脑脊液中通95% N₂+5% CO₂诱导。通过测定TTC染色后形成的红色产物来分析脑片活性。结果氟哌啶醇(1和10 μmol·L^-1)抑制OGD损伤,抑制率分别为17.7%和25%,而D₂多巴胺受体拮抗剂多潘立酮无此作用。NMDA也能显著降低海马脑片及原代神经元的活性,而氟哌啶醇可抑制这一损伤作用。结论氟哌啶醇对大鼠离体海马脑片OGD和原代神经元NMDA损伤有保护作用。     

抗肿瘤抗生素1588的研究——Ⅲ.对动物移植性肿瘤实验治疗研究

本文报告抗生素1588对多种移植性动物肿瘤的实验治疗研究。结果表明抗生素1588按12.5 mg/kg连续给药10天,对小鼠S-180、U-14、Lio-1和B₂₂等实体癌均有明显的抑制作用。并能延长E_c、ARS,HCA等腹水癌小鼠及Walker-256(腹水型)大鼠的生命时间。但对小鼠白血病L₆₁₅无效。此外还报告了不同给药方案对S-180抑制作用的影响。本文还研究了抗生素1588的二个主要组分即1588-74-3及1588-74-9对小鼠S-180的抗肿瘤作用,并与争光霉素和平阳霉素进行了比较。     

2,4-二氨基-5-氯-6-取代苄氨基喹唑啉类化合物的合成及其抗疟、抗肿瘤和抗菌活性

本文报道标题化合物的合成及其抗疟、抗肿瘤和抗菌活性,该类化合物是以5-氯-2,4, 6-三氨基喹唑啉与各种取代苯甲醛缩合成相应的Schiff碱,然后经NaBH₄还原,再甲酰化或亚硝化制得.经对感染伯氏疟原虫(P.berghei)的鼠抑制性治疗筛选,有八个化合物剂量20mg/kg×4d时抑制率100%,Ⅰ₃,Ⅰ₄,Ⅲ₄三个化合物剂量5mg/kg×4d时抑制率在90%以上;体外抗肿瘤试验有4个化合物的活性优于MTX和SIPl759,以Ⅰ₄最佳。对L1210白血病细胞株的IC₅₀为2.20×10^-9 m mol/L;经对18种常用菌株进行体外筛选,发现对肺炎双球菌(D.pneumoniae)有较好的活性。     

不同首剂量的牛肺表面活性剂对新生儿呼吸窘迫综合征的疗效

目的 通过分析肺表面活性物质（PS）的不同首剂量对新生儿呼吸窘迫综合征（NRDS）的临床疗效。方法 选取2015年4月—2018年3月在平顶山市第一人民医院收治确诊的NRDS 100例作为研究对象,采用随机数字表法分为70 mg/kg剂量组和100 mg/kg剂量组,每组各50例,分别给予注射用牛肺表面活性剂首剂量70、100 mg/kg出生体质量的治疗剂量。比较两组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率及治疗前后的氧分压（pO₂）、二氧化碳分压（pCO₂）、吸入氧浓度（FiO₂）、平均动脉压（MAP）。结果 治疗后,100 mg/kg组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率均低于70 mg/kg组,差异均有统计学意义（P<0.05）,但两组患儿住院时间相比没有显著差异。两组患儿经过治疗后pO₂、pCO₂、FiO₂、MAP均优于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）,其中100 mg/kg组患儿治疗后pCO₂、FiO₂、MAP明显优于70 mg/kg组,差异有统计学意义（P<0.05）,但治疗后两组pO₂差异无统计学意义。结论 注射用牛肺表面活性剂首剂量100 mg/kg出生体质量应用于新生儿呼吸窘迫综合症,能有效显著缩短患儿的氧疗时间及住院时间,降低住院肺炎发生率,具有较好的临床应用价值。     

Effect of Cimetidine on the Pharmacokinetics and Pharmacodynamics of Chlorpheniramine and Diphenhydramine in Rabbits

Purpose. The effects of concomitant administration of the H₂-receptor antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H₁-receptor antagonists chlorpheniramine and diphenhydramine were studied in rabbits. Methods. A single dose of chlorpheniramine 10 mg (Group A) or diphenhydramine 10 mg (Group B) was given intravenously on three different study days as follows: 2 weeks before cimetidine administration, after giving cimetidine 100 mg/kg intravenously every 12 hours for one week, and two weeks after discontinuing the cimetidine. Serum chlorpheniramine and diphenhydramine concentrations were measured by HPLC. Histamine H₁-blockade was assessed by measuring suppression of the histamine-induced wheals in the skin. Results. The chlorpheniramine and diphenhydramine terminal elimination half-life values and area under the curve values were significantly increased, and the systemic clearance rates were significantly decreased, during concomitant administration of cimetidine. For each H₁-receptor antagonist, pharmacokinetic parameters were similar before cimetidine was co-administered and two weeks after cimetidine was discontinued. Wheal suppression produced by chlorpheniramine or diphenhydramine was increased and prolonged when cimetidine was administered concomitantly. Conclusions. Any enhanced peripheral H₁-blockade observed could be attributed, at least in part, to a pharmacokinetic interaction.     

Weight-adjusted versus fixed dose of linezolid for Chinese healthy volunteers of higher and lower body weight: a Phase I pharmacokinetic and pharmacodynamic study

Objectives: The objective was to evaluate the pharmacokinetic and pharmacodynamic properties of a single intravenous fixed dose compared with a weight-adjusted dose of linezolid.

Methods: A Phase I, comparative clinical trial was conducted involving 20 healthy male Chinese volunteers, assigned into low weight (LW) (50 kg < weight ≤ 55 kg) and high weight (HW) (≥ 80 kg) groups. All subjects were administrated single dose of linezolid (600 mg/30 min) and, after 72 h washout period, another single-dose (10 mg/kg/30 min). Plasma linezolid concentrations were measured by liquid chromatography-tandem mass spectrometry. A Monte Carlo simulation was used to evaluate the probability of pharmacodynamic target attainment (PTA).

Results: With 600 mg dose, plasma concentrations in LW group were much higher than that in HW group. A persistent serum inhibitory activity was observed in LW group; the inhibitory activity was lower in HW group. The PTA in HW group was lower than in LW group. For 10 mg/kg dose, both HW and LW groups had similar plasma concentrations. The HW and LW groups had similar serum inhibitory effects. The PTA in HW and LW groups also showed no difference.

Conclusions: Our findings suggest that a weight-adjusted, 10 mg/kg regimen of linezolid may be more appropriate than fixed dosing for patients of different body weight.     

Selective effects of the D1 dopamine receptor agonist,SKF 38393, on behavior maintained by cocaine injection in squirrel monkeys

The effects of the dopamine receptor D₁ partial agonist, SKF 38393, on behavior maintained by cocaine was assessed in squirrel monkeys (Saimiri sciureus). One group of subjects was trained to press a key under a fixed-ratio 30-response schedule of cocaine injection; when green stimulus lamps were illuminated each 30th response produced an injection (17 µg/kg) followed by a 1-min period during which the lights were out and responses had no scheduled consequences. Another group of squirrel monkeys was trained under an identical schedule with food reinforcement. SKF 38393 produced dose-related decreases in rates of responding maintained by either cocaine injection or food presentation. Rates of responding maintained by cocaine were decreased to a greater extent than those maintained by food. The ED₅₀ value for SKF 38393 for responding maintained by cocaine was 2.53 mg/kg (95% CL: 1.22–5.23), whereas that value was 15.63 mg/kg (95% CL: 2.83–86.33) for responding maintained by food. Rates of responding maintained by cocaine were an inverted-U-shaped function of dose. Pretreatment with 3.0 mg/kg SKF 38393 shifted the ascending limb of the cocaine dose-effect curve to the right. These findings suggest that indirect D₁-receptor activation plays a role in the reinforcing effects of cocaine, and that drugs acting at D₁ receptors may show promise as therapeutic agents in the treatment of cocaine abuse.     

制川乌配方颗粒与标准煎剂对二甲苯致小鼠耳肿胀抑制作用的比较研究

目的 对制川乌配方颗粒与标准煎剂抗炎药效等效性进行研究。方法 应用二甲苯致小鼠耳肿胀法比较制川乌标准煎剂及配方颗粒对其抑制作用。结果 在抗炎药效等效性研究中,在小鼠耳廓肿胀抑制率22.51%～38.65%共同效应范围内,1/2、1、2倍临床等效剂量（195.00、390.00、780.00 mg/kg）制川乌标准煎剂等效于0.07、0.20、0.46倍临床等效剂量（27.36、77.67、178.29 mg/kg）制川乌配方颗粒所产生的抗炎效应,制川乌配方颗粒等效剂量DEE_{制川乌配方颗粒}=-22.950＋0.258× DEE_{制川乌标准煎剂}（R²=0.958,r=0.979,P<0.01）,回归系数b₀=-22.950,95% CI为（4.549,41.351）,与总体均值0相比,差异有显著性（P<0.05）,常数项b₁=0.258,95% CI为（-0.218,0.299）,与总体均值1相比,差异有显著性（P<0.05）。制川乌配方颗粒与制川乌标准煎剂药剂量在1/8～1倍临床等效应剂量范围内（48.75～390.00 mg/kg）具有可比性,制川乌配方颗粒的等剂量效应EED_{制川乌配方颗粒}=2.963＋1.573×EED_{制川乌标准煎剂}（R²=0.923,r=0.961,P<0.01）,回归系数b₀=2.963,95% CI为（-5.373,11.300）,与总体0比较差异有显著性（P<0.05）,常数项b₁=1.573,95% CI为（1.230,1.915）,与总体均值1相比差异有显著性（P<0.05）。结论 在抗炎方面制川乌配方颗粒和制川乌标准煎剂的等效应剂量不具有等效性,制川乌配方颗粒等效应剂量较制川乌标准煎剂小。在抗炎方面制川乌配方颗粒和制川乌标准煎剂的等剂量效应不具有等效性,制川乌配方颗粒等剂量效应较制川乌标准煎剂大。     

Gymnemic Acids from Gymnema sylvestre. Potentially Regulates Dexamethasone-Induced Hyperglycemia in Mice

ABSTRACT

Effects of three different doses (6.7, 13.4, and 26.8 mg/kg body wt., i.p.) of gymnemic acids (GA) from the leaves of Gymnema sylvestre. R. Br. in the regulation of dexamethasone induced hyperglycemia have been investigated in mice. Simultaneously, thyroid hormone levels were estimated by radioimmunoassay (RIA) in order to find out whether the effects are mediated through alteration in the thyroid function or not. While the prestandardized dose (1 mg/kg body wt., i.m.) of dexamethasone administration for 22 days increased the serum glucose concentration, it decreased serum concentration of the thyroid hormones thyroxine (T₄) and triiodothyronine (T₃). Although the administration of all three different doses of gymnemic acid decreased the serum glucose concentration in dexamethasone-induced hyperglycemic animals, the decrease was significant only in groups receiving the two higher doses, 13.4 and 26.8 mg/kg. These effects were comparable to a standard corticosteroid-inhibiting drug, ketoconazole. However, the percentage reduction was greater in the 13.4 and 26.8 mg/kg of gymnemic acids–treated groups (28.76% and 21.71% respectively) as compared to that of ketoconazole, where it was only 9.07%. As no significant changes in thyroid hormone concentrations were observed by the administration of any of the doses of GA in dexamethasone-treated animals, it further appears that the effects of the tested material might not have been mediated through alterations in the thyroid function. The changes in hepatic lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT) activity revealed a toxic effect at the highest dose (26.8 mg/kg body wt.) as evidenced by increased LPO, whereas the medium dose (13.4 mg/kg body wt.) was found to be safe and antiperoxidative. It is suggested that 13.4 mg/kg of gymnemic acids may prove to be potentially effective in the amelioration of corticosteroid-induced diabetes mellitus/hyperglycemia.     

Antitumor and Cytotoxic Investigation of Amoora Rohituka

Abstract

An ethyl acetate extract derived from the stem bark of Amoora rohituka exhibited antitumor activity on mice inoculated with Dalton's lymphoma ascites cells (DLA). Intraperitoneal administration of the extract at doses of 10 or 20 mg/kg/day prolonged the median survival time of the animals. It showed cytotoxicity against Dalton 's lymphoma ascites cells with a 50% inhibitory concentration (IC₅₀) of 9 μg/ml, with no activity against Hep-2 cells from a tumor of the larynx.     

The effect of resveratrol on pharmacokinetics of aripiprazole in vivo and in vitro

1.?The objective of this study were to investigate the effect of orally administered resveratrol on the pharmacokinetics of aripiprazole (APZ) in rat, and the inhibitory effects of resveratrol on APZ dehydrogenation activity in liver microsomes and human cytochrome P450 3A4 and 2D6.

2.?Twenty-five healthy male Sprague–Dawley rats were randomly divided into five groups: A (control group), B (multiple dose of 200?mg/kg resveratrol), C (multiple dose of 100?mg/kg resveratrol), D (a single dose of 200?mg/kg resveratrol) and E (a single dose of 100?mg/kg resveratrol). A single dose of 3?mg/kg APZ administered orally 30?min after administration of resveratrol. In addition, CYP2D6*1, CYP3A4*1, human and rat liver microsomes were performed to determine the effect of resveratrol on the metabolism of APZ in vitro.

3.?The multiple dose of 200 or 100?mg/kg resveratrol significantly increased the AUC and C_max of APZ. The resveratrol also obviously decreased the CL, but without any significant difference on t_1/2 in vivo. On the other hand, resveratrol showed inhibitory effect on CYP3A4*1, CYP2D6*1, human and rat microsomes, the IC₅₀ of resveratrol was 6.771, 87.87, 45.11 and 35.59?μmol?l^?1, respectively.

4.?Those results indicated more attention should be paid when APZ was administrated combined with resveratrol.