Combined antitumor effect of cyclophosphamide and bromodeoxyuridine in BDF1 mice bearing L1210 ascites tumors

We investigated the combined effect of cyclophosphamide (CPA) and 5-bromo-2'-deoxyuridine (BrdUrd) both in mice bearing L1210 ascites tumors and in L1210 leukemic cells in vitro. Administration of BrdUrd (100 mg/kg) for 5 consecutive days before a single dose (80 mg/kg) of CPA significantly extended the survival of mice by 158%, compared with CPA alone. BrdUrd administered at daily doses of 100 or 200 mg/kg for 5 consecutive days did not extended the survival of mice. An in vitro MTT assay revealed that BrdUrd enhanced the cytotoxic effect of 4-hydroxycyclophosphamide, an active form of CPA, in the L1210 cells. These results indicate that BrdUrd enhanced the antitumor effect of CPA both in vivo and in vitro.     

Effect of subchronic aflatoxin exposure on growth and progression of Ehrlich's ascites tumor in mice

The present investigation was undertaken to assess whether aflatoxin B1 (AFB1) has any modulatory effect on the growth and progression of Ehrlich's ascites tumor (EAT) in mice or not. Male Swiss albino mice were treated with 0, 70, 350 and 700 micrograms AFB1/kg body weight in 0.2 ml corn oil on alternate days, orally, for two weeks. Treated animals were challenged with 1 x 10(6) cells of Ehrlich's ascites tumor. Animals were monitored for the appearance of palpable tumor, body weight gain as a measure of tumor burden, mortality profile and tumor cell population. Some parameters of cell mediated immunity (CMI), humoral immunity and non-specific immunity were also studied in aflatoxin treated animals in order to find out the mechanism of action of AFB1 on host immunity. It was observed that AFB1 treatment resulted in an early appearance of tumor, enhanced mortality, appreciable increase in body weight gain and EAT cell population following tumor challenge, in comparison with the control animals. Aflatoxin treatment caused suppression of CMI including an impairment of macrophage function, while humoral immunity was not much affected. It may be concluded that impaired CMI and macrophage function might be contributing to the increased growth of EAT in the AFB1 treated animals. Our findings may be relevant in that when a host is exposed to aflatoxins concomitantly with other carcinogens and cancer causing situations.     

Effect of carbon disulfide on the anticholinesterase action of several organophosphorus insecticides in mice

Effect of carbon disulfide (CS2) on toxic action of 11 organophosphorus (OP) insecticides were examined by determining the plasma cholinesterase activity in mice. CS2 pretreatment potentiated the anticholinesterase action of parathion and EPN, but suppressed that of dimethoate and diazinon. CS2 had no significant effect or a slightly suppressive effect on the other compounds. Some of these effects were contrasted with the reported alteration of the toxicity following phenobarbital pretreatment. CS2 administration suppressed both detoxification and activation of parathion and EPN by liver microsomes in vitro, as measured by p-nitrophenol production and cholinesterase inhibition, respectively. Causal relationship between the in vitro and in vivo observations, however, remains to be clarified.     

蟾蜍毒素对S180小鼠移植瘤的抑制作用及其毒副作用的实验研究

目的探讨醇溶性蟾蜍毒素在小鼠体内对S180肿瘤细胞的抑制作用及其毒副作用。方法本研究用乙醇溶解蟾蜍分泌物原浆,采用减压蒸馏等方法进一步部分分离纯化,获得醇溶性的蟾蜍毒素混合物(ethanol extract of toad venom,EET),将其作用于S180荷瘤小鼠模型,计算肿瘤抑制率和生命延长率,同时通过血生化和病理等检测观察其对各脏器的毒副作用。结果5mg/kg和0·5mg/kg的EET对S180荷瘤小鼠实体瘤组织的抑瘤率分别是47·0%和34·1%(P<0·05);对腹水瘤小鼠的生命延长率分别是46·2%和36·5%(P<0·05);同时,0·5mg/kg的EET可明显升高白细胞达(11±4)×109/L(P<0·05)。但EET在5mg/kg时可引起总胆红素升高达(30±5)μmol/L(P<0·05)。结论0·5~5mg/kg的EET可以明显抑制荷瘤小鼠体内S180肿瘤细胞的生长,但EET的剂量达到5mg/kg时可以损伤肝脏。     

The in vivo effect of a Brassica oleracea var. capitata extract on Ehrlich ascites tumors of MUS musculus BALB/C mice

An extract of Brassica oleracea var. capitata juice was prepared using petroleum ether, ether, ethanol and an Al2O3 column. The healing and tumor protecting effects of this extract were tested on Ehrlich ascites (EA) solid tumors of Mus musculus BALB/C mice. Complete disappearance of the tumors was observed in 54.5% of the animals in the experimental group (n = 22) which received 20 mg/day of the extract i.p. for 28 days. Regression of the tumors (27%), fixation of tumor size (4%) and an increase in tumor size (18%) were also recorded. Neither tumor size fixation nor regression was recorded in the control group which received physiological serum (0.5 ml/day). The healing effect was found to be related to the starting tumor size. The healed animals in the experimental group were followed for 6-7 months and no tumor recurrence was recorded. The protective effect of this extract on tumor formation was also tested. Experimental animals (n = 35) received 20 mg/day of the extract i.p. for 20 days. Physiological serum was administered to a control group (n = 30). Transplantation of solid tumors was performed on the 20th day and extract administration was discontinued. Transplantation success was recorded 20 days after transplantation. In the experimental group, only three out of 35 mice showed tumor development, whereas in the control group the number was 23 out of 35 mice. It was also observed that the extract prevented the development of liquid EA tumors. This extract was also found to be nontoxic. Brassica oleracea var. capitata had a healing effect as well as a protective effect on EA solid tumors of mice. These results are in agreement with our previous results obtained from a liquid Brassica oleracea var. acephala juice extract.     

Effect of chlorpromazine and quinacrine on the lethality in mice of the venoms and neurotoxins from several snakes

Antivenoms are the currently available agents for the treatment of intoxication by snake venoms. Therapeutic approaches using more generally available drugs could improve treatment of envenomation by reducing the cost of the therapeutic agent, eliminating hypersensitivity reactions to antivenoms, and reducing storage costs. I investigated the efficacies of chlorpromazine and quinacrine with respect to reducing the lethality in mice of Bungarus caeruleus venom, Bungarus multicinctus venom and its neurotoxic components alpha- and beta-bungarotoxin, Crotalus durissus terrificus venom and its neurotoxic component crotoxin, and Oxyuranus scutellatus venom and its neurotoxic component taipoxin. Venom or toxin was administered i.p., followed immediately by an i.p. injection of chlorpromazine or quinacrine. The effect of drug on the lethality of the venom was recorded 24 hr later. Chlorpromazine and quinacrine were effective antagonists of the lethality of B. caeruleus venom, B multicinctus venom, and beta-bungarotoxin without themselves being overtly toxic. Chlorpromazine (1 mg/kg) increased the LD50 of B. caeruleus venom, B. multicinctus venom, and beta-bungarotoxin by 8.6-, 2.6- and 3.7-fold, respectively. In the range of 1 to 5 mg/kg, quinacrine increased the LD50 of B. caeruleus venom, B. multicinctus venom and beta-bungarotoxin by 5.7-, 11- and 8.6-fold, respectively. Neither drug had any effect on the other venoms or toxins. Chlorpromazine and quinacrine were also injected at different times both before and after the injection of venom or toxin. Protection from lethality was maximal for both drugs when they were administered immediately after injection of venom or toxin.     

Synergistic effects of irinotecan and flavonoids on Ehrlich ascites tumour-bearing mice

Swiss albino mice were given Ehrlich ascites tumour cells (1 × 10(6)) intraperitoneally. For survival analysis and tumour growth analysis, the mice were administered quercetin and naringin (100 mg/kg) daily for 3 consecutive days, beginning on the third day after intraperitoneal (i.p.) injection of Ehrlich ascites tumour cells (1 × 10(6)). Irinotecan was administered ip at a dose of 50 mg/kg on days 1, 13 and 19. For the analysis of cell types and differential count of cells present in the peritoneal cavity, peripheral whole-blood leucocyte count and the comet assay, the mice were treated therapeutically with quercetin and naringin (100 mg/kg) and irinotecan (50 mg/kg) daily for 3 consecutive days beginning on third day after i.p. injection of Ehrlich ascites tumour cells (1 × 10(6)). We observed the synergistic anti-tumour effect expressed as the median survival time of mice treated with naringin in combination with irinotecan. All test components inhibited tumour growth and increased lifespan of mice except quercetin. The total number of cells present in the peritoneal cavity of mice significantly decreased in all treatments except quercetin. Single irinotecan and irinotecan combined with naringin had the highest DNA-damaging potential on peripheral blood leucocytes and lowest primary DNA damage, both in the kidney and liver cells as measured by the alkaline comet assay. Our results showed enhanced anti-tumour activity of irinotecan in combined treatment with flavonoids to reduce the deteriorating reaction of cytostatic drugs.     

重组人血管内皮抑素治疗小鼠恶性腹腔积液疗效及作用机制研究

目的：研究重组人血管内皮抑素（恩度）治疗小鼠恶性腹腔积液的疗效及作用机制。方法：用小鼠H22细胞系建立小鼠恶性腹水瘤模型。120只ICR小鼠随机分为5组：对照组（0．9％NS）,恩度组1（恩度8mg／kg）,恩度组2（造模后24h开始给予恩度8mg／kg）,联合组（顺铂1mg／kg＋恩度8mg／kg）,顺铂组（顺铂1mg／kg）,恩度组2从造模后24h开始给药,其余各组从第6天开始给药,顺铂5d,恩度6d,均为1次／d。记录各组小鼠体重、腹水体积、生存期和明显不良反应;测定小鼠腹水伊文思蓝的吸光度值间接反映小鼠腹膜通透性;采用ELISA法测定小鼠血清、腹水中血管内皮生长因子（VEGF）、基质金属蛋白酶-2（MMP-2）浓度。结果：与对照组比较,各实验组均能抑制小鼠腹水生成、延长小鼠生存期,降低小鼠腹膜通透性及小鼠血清、腹水中VEGF、MMP-2水平（P〈0．05）,以联合组较明显。结论：恩度联合顺铂治疗小鼠恶性腹腔积液疗效优于恩度、顺铂单药,其作用机制可能为联合用药进一步降低了小鼠血清、腹水中VEGF、MMP-2水平。     

Effects in vivo of lymphoma ascites tumors and procarbazine, alone and in combination, upon hepatic drug- metabolizing enzymes of mice.

Studies have been conducted on hepatic microsomal enzymes after treatment of two strains of male mice, BDF₁ and DBA/2J, each with a single dose (300 mg/kg body weight) of procarbazine (PCZ) hydrochloride alone or in combination with a 6- to 7-day prior implantation of murine leukemic lymphoma L5178Y ascites cells. Mice were sacrificed at 4, 8 or 16 hr after i.p. injection of PCZ and found to possess levels of microsomal aniline hydroxylase, ethylmorphine N-demethylase, nitrobenzoate reductase activities and cytochrome P-450 content which were depressed to 78, 76, 54 and 61 per cent of untreated controls, respectively, for BDF₁ mice and 61, 51, 39 and 51 per cent of untreated controls, respectively, for DBA/2J mice. Mice implanted with lymphoma cells and sacrificed 6–7 days later without PCZ treatment had hepatic microsomal enzyme activity levels which were depressed to about the same extent as those receiving PCZ treatment only. PCZ treatment 6–7 days after lymphoma implantation caused severe depression of microsomal enzyme activities in both mouse strains. The maximum depressions expressed as per cent of untreated controls were: cytochrome P-450, 33 per cent; aniline hydroxylase, 32 per cent; ethylmorphine N-demethylase, 33 per cent; and nitrobenzoate reductase, 33 per cent. As a possible explanation for the PCZ effects, it is proposed that PCZ is serving as a tightly bound competitive substrate to cytochrome P-450-related enzyme systems.     

胰岛素对数种缩血管物质作用的影响

目的 观察胰岛素对去甲肾上腺素、内皮素-１、氯化钾（ＫＣＩ）、血管紧张素Ⅱ和５－羟色胺缩血管作用的影响。方法 用ＳＤ大鼠的离体动脉血管观察缩血管物质的作用。结果 在含有１ｍＵ／ｍｌ胰岛素环境中，胰岛素对数种缩血管作用机制不同的物质有程度不同的血管增敏作用。对去甲肾上腺素、内皮素－１和ＫＣＩ有明显的增敏效果；对血管紧张素Ⅱ有增敏趋势，但无显著性差异；对5－羟色胺无增敏效应。结论 胰岛素在高血压的发病过程中可能起重要作用。     

探究射频热疗在恶性腹水治疗中的临床疗效

目的探究射频热疗在恶性腹水的综合治疗中的临床疗效,为恶性腹水的治疗提供参考经验。方法选取2009年10月—2011年5月恶性腹水患者85例,包括卵巢癌32例,胃癌16例,肝癌11例,胰腺癌5例,结肠直肠癌15例,乳腺癌6例,随机分为治疗组和对照组。治疗组给予局部射频热疗联合腹腔灌注化疗药物,对照组只给予腹腔灌注化疗药物。观察两组的腹水消退情况、卡氏评分变化及治疗中出现的不良反应。结果治疗组有效率(CR+PR)75.6%,卡氏评分升高率76.2%,与对照组有明显差异(P<0.05),而且不良反应两组间无明显差异(P>0.05)。结论局部射频热疗联合腹腔灌注化疗药物治疗恶性腹水效果更好,且不增加不良反应,值得推广。     

Analgesic effects of several calcium channel blockers in mice

The possibility that calcium channel blockers might produce antinociception and increase morphine analgesia was examined using the acetic acid writhing test in mice. Subcutaneous injections of diltiazem, verapamil, nicardipine, flunarizine and cinnarizine produced a dose-dependent antinociception. This activity of diltiazem was stereospecific; d-cis-diltiazem was more potent than 1-cis-diltiazem. All the calcium channel blockers studied increased morphine analgesia and displaced to the left the morphine dose-response curve. This effect of diltiazem was also stereospecific. These results suggest that calcium channel blockers can induce analgesia and increase morphine analgesia, possibly through a decrease in cellular calcium availability.