四物汤与十全大补汤的抗突变作用研究

用姐妹染色单体互换技术检测中药方剂四物汤、十全大补汤，发现其能明显降低环磷酰胺所致的ＳＣＥ值升高，表明有抗突变作用。     

自由基清除剂对环磷酰胺致大鼠血清和卵巢MDA含量及SOD活性的影响

本文观察了自由基清除剂ＶｉｔＥ，ＶｉｔＣ和别嘌呤醇对环磷酰胺致幼年雌性大鼠血清和卵巢ＭＤＡ含量及ＳＯＤ活性的变化。结果显示，加自由基清除剂组大鼠血清和卵巢ＭＤＡ含量及ＳＯＤ活性分别明显低于和高于环磷酰胺组。表明自由基清除剂ＶｉｔＥ、ＶｉｔＣ和别嘌呤醇能有效地清除大鼠血和性腺中的自由基，对环磷酰胺所致大鼠卵巢毒性有一定的对抗作用。     

化疗药对病毒瘤苗免疫效果的影响

不同化疗药作用过肿瘤细胞，经病毒染后制成瘤苗的免疫效果明显不同，环磷酰胺和地塞米松能增强肿瘤细胞的抗原性，病毒感染后制备的瘤苗免疫力也随之增强，而阿糖胞苷对肿瘤细胞无影响，处理过的肿瘤细胞经病毒感染后制备的瘤苗抗原性反而降低，环磷酰胺预先处理荷瘤小鼠腹腔的肿瘤细胞，可去除Ｔｓ细胞的作用，保持新城疫病毒－瘤苗的免疫效果，提高受攻击小鼠的存活率。     

自由基消除剂对环磷酰胺致大鼠血清和卵巢MDA含量及SOD活…

本文观察了自由基清除剂ＶｉｔＥ、ＶｉｔＣ和别嘌呤醇对环磷酰胺致幼年雌性大鼠血清和卵巢ＭＤＡ含量及ＳＯＤ活性的变化。结果显示，加自由基清除剂组大鼠血清和卵巢ＭＤＡ含量及ＳＯＤ活性分别明显低于和高于环磷酰胺组。表明自由基清除剂Ｖｉｔ Ｅ、Ｖｉｔ Ｃ和别嘌呤醇能有效地清除大鼠血和性腺中的自由基，对环磷酰胺所致大鼠卵巢毒性有一定的对抗作用。     

八珍汤对血虚模型小鼠造血调控因子影响的实验研究

探讨八珍汤对由环磷酰胺引起的小鼠骨髓造血功能抑制的调控作用。采用环磷酰胺致小鼠血虚模型 ,测定八珍汤对骨髓抑制小鼠外周血象及其细胞因子产生的影响。结果表明 ,八珍汤对环磷酰胺所致血虚模型小鼠骨髓细胞有促进增殖作用 ;经八珍汤诱导制备的巨噬细胞、脾细胞、肺条件培养液和骨骼肌条件培养液能促进血虚模型小鼠骨髓细胞增殖 ,促进血虚模型小鼠骨髓基质细胞分泌肿瘤坏死因子 (TNF)。八珍汤对环磷酰胺所致化疗损伤的造血调控作用可能与直接或间接刺激造血微环境的基质细胞分泌正性和负性造血生长因子有关。     

毛蚶提取物对环磷酰胺增效减毒作用的研究

研究毛蚶提取物对环磷酰胺的增效和减毒作用。采用腹水型S180小鼠和免疫低下小鼠模型为实验对象,以其抑瘤率、白细胞、巨细胞吞噬功能、溶血素水平和胸腺、脾脏指数为指标,评价毛蚶提取物对环磷酰胺的增效减毒作用。毛蚶提取物(100、200、400 mg·kg-1,i.g)与环磷酰胺合用比单用环磷酰胺抑瘤率明显提高,明显抑制环磷酰胺引起的白细胞下降,提高了免疫低下小鼠单核吞噬细胞的吞噬功能,提高了小鼠溶血素水平和免疫器官指数。毛蚶提取物通过免疫调节作用对环磷酰胺有明显的增效减毒作用。     

IL－2和环磷酰胺体内增强TNF基因转染瘤苗的抗肿瘤作用

应用细胞因子基因转染的瘤苗进行肿瘤治疗是一条值得探讨的新途径。本研究将放射线灭活的ＴＮＦ－α基因转染的肿瘤细胞作为瘤苗联合低剂量ＩＬ－２和／或低剂量环磷酰胺治疗实验性肺转移荷瘤小鼠，结果发现单独应用ＴＮＦ基因转染的瘤苗无明显疗效，但联合低剂量ＩＬ－２或低剂量ＩＬ－２加低剂量环磷酰胺后具有显著的抗肿瘤转移作用。本研究表明，低剂量ＩＬ－２和低剂量环磷酰胺对ＴＮＦ基因转染瘤苗的抗肿瘤转移作用有增强效应。     

IL—2和环磷酰胺体内增强TNF基因转染瘤苗的抗肿瘤作用

应用细胞因子基因转染的瘤苗进行肿瘤治疗是一条值得探讨的新途径。本研究将放射线灭活的ＴＮＦ－ａ基因转染的肿瘤细胞作为瘤苗联合低剂量ＩＬ－２和／或低剂量环磷酰胺治疗实验性肺转移荷瘤小鼠，结果发现单独应用ＴＮＦ基因转染的瘤苗无明显疗效，但联合低剂量ＩＬ－２或低剂量ＩＬ－２加低剂量环磷酰胺后具有显著的抗肿瘤转移作用。本研究表明，低剂量ＩＬ－２和低剂量环磷酰胺对ＴＮＦ基因转染瘤苗的抗肿瘤转移作用有增强效应。     

养胃合剂对环磷酰胺化疗荷瘤小鼠骨髓抑制的影响

目的：观察养胃合剂对环磷酰胺化疗荷瘤小鼠骨髓抑制的影响。方法：对C57BL小鼠进行肉瘤180（S180）接种造模，给予养胃合剂灌胃和环磷酰胺（CTX）腹腔注射，停药24h后，将各组小鼠断颈处死，每只小鼠取左侧股骨干，冲洗股骨骨髓，计数骨髓有核细胞。结果：用高、低剂量养胃合剂的荷瘤化疗小鼠骨髓有核细胞数，均显著高于荷瘤化疗组（P＜0．01）。结论：养胃合剂能减轻环磷酰胺化疗荷瘤小鼠的骨髓抑制。     

环磷酰胺药效、副作用和药物动力学依时特征

目的 探索环磷酰胺药效、副作用和药物动力学依时特征。方法 通过监测S(?)实体瘤小鼠的瘤重、外周血白细胞计数、淋巴细胞百分率、骨髓细胞计数评价昼夜不同时间环磷酰胺给药的反应。通过大鼠血药浓度监测和药物动力学参数分析,探索不同时间环磷酰胺给药的动力学模式。结果 环磷酰胺晚上给药血药浓度高、毒性大、作用强,早上给药毒性小,药物作用足以达到治疗效果。结论 环磷酰胺对于小鼠早上给药副作用小。     

DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with 60Co gamma-rays also induced DNA strand breaks. The elution profiles for gamma-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than gamma-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice.     

Acquisition of coinfection and simultaneous transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis ticks

The agents of Lyme disease (Borrelia burgdorferi) and human granulocytic ehrlichiosis (Ehrlichia phagocytophila) are both transmitted by the tick Ixodes scapularis. In nature, ticks are often infected with both agents simultaneously. We studied whether previous infection with either Borrelia or Ehrlichia in ticks would affect acquisition and transmission of a second pathogen. Ehrlichia-infected I. scapularis nymphs were fed upon Borrelia-infected mice, and Borrelia-infected I. scapularis nymphs were fed upon Ehrlichia-infected mice. The efficiency with which previously infected nymphal ticks acquired a second pathogen from infected hosts was compared to that of uninfected ticks. An average of 51% +/- 15% of ticks acquired Ehrlichia from infected mice regardless of their prior infection status with Borrelia. An average of 85% +/- 10% of ticks acquired Borrelia from infected mice regardless of their prior infection status with Ehrlichia. Also, we assessed the efficiency with which individual nymphs could transmit either agent alone, or both agents simultaneously, to individual susceptible hosts. An average of 76% +/- 9% of Borrelia-infected ticks and 84% +/- 10% of Ehrlichia-infected ticks transmitted these agents to mice regardless of the presence of the other pathogen. There was no evidence of interaction between the agents of Lyme disease and human granulocytic ehrlichiosis in I. scapularis ticks. The presence of either agent in the ticks did not affect acquisition of the other agent from an infected host. Transmission of the agents of Lyme disease and human granulocytic ehrlichiosis by individual ticks was equally efficient and independent. Dually infected ticks transmitted each pathogen to susceptible hosts as efficiently as ticks infected with only one pathogen.     

Histamine hypersensitivity in mice induced by concanavalin A

This study compared the responses of CFW and CFI mice to concanavalin A (con A) and the histamine-sensitizing factor (HSF) of Bordetella pertussis. There were marked similarities between these two agents with regard to systems implicated in induced histamine sensitivity. Con A, like HSF, induces the sensitivity in CFW but not in CFI mice. The sensitizing agents both require the same time for optimum sensitization, both induce cutaneous sensitivities to histamine, and the mice are protected from the induced susceptibility of both agents by epinephrine and by desensitization with serotonin. They differed in that con A did not induce the systemic susceptibility to serotonin or to combined histamine and serotonin which is produced by HSF. The major difference related to mechanisms of action was the failure of con A to induce a systemic beta-adrenergic blockade, the block of which is manifested in HSF-treated CFW and CFI mice by the inhibition of an epinephrine-induced hyperglycemia. The resistance of beta-blocked CFI mice to histamine, and the susceptibility to histamine of the unblocked CFW mice sensitized with con A, is inconsistent with the theory that susceptibility results from a systemic adrenergic imbalance, but does not preclude a local adrenergic effect as the common element in histamine-sensitizing agents.     

Zinc content in pancreatic islets in experimental diabetes induced by chelating agents]

The zinc content in microresected islets of rabbits, mice, rats, and guinea pigs was determined by atom-absorption spectrophotometry. The content was found to be highest in rabbits, and diabetes was induced in them by chelating agents easily. Injection of dithizone or 8-(p-toluenesulfonylamine) quinoline failed to induce diabetes mellitus in mice, rats, and guinea pigs. It is concluded that diabetogenic chelating agents are capable of producing irreversible diabetogenic affection in those beta-cells which contain a critical concentration of reactant zinc.     

Simultaneous serodetection of 10 highly prevalent mouse infectious pathogens in a single reaction by multiplex analysis

Under current practices of mouse colony maintenance, sera from mice are analyzed for antibodies against several widespread infectious pathogens by conventional immunoassays, generally enzyme-linked immunosorbent assay (ELISA). To test for multiple agents, these methods consume large volumes of mouse serum and are laborious and time-consuming. More efficient immunoassays, using small amounts of sample, are therefore needed. Accordingly, we have developed a novel multiplex diagnostic system that employs fluorescent microbeads, coated with purified antigens, for simultaneous serodetection of 10 mouse infectious agents. Individually identifiable, fluorescent microbeads were coated with antigens from Sendai virus, mouse hepatitis virus, Theiler's mouse encephalomyelitis virus/GDVII strain, mouse minute virus, mouse cytomegalovirus, respiratory enteric orphan virus (Reo-3 virus), mouse parvovirus, calf rotavirus for epizootic diarrhea virus of infant mice, vaccinia virus for ectromelia virus, and Mycoplasma pulmonis. Standard sera, singly positive for antibodies to individual infectious agents, were generated by inoculation of BALB/cj and C57BL/6j mice. Sera from these experimentally infected mice, as well as sera from naturally infected mice, were analyzed using a mixture of microbeads coated with antigens of the 10 infectious agents listed above. Results demonstrated that the multiplex assay was at least as sensitive and specific as ELISA for serodetection. Importantly, the multiplex assay required only 1 microliter of serum for simultaneous serodetection of the 10 mouse infectious agents in one reaction vessel. Thus, this multiplex microbead assay is a reliable, efficient, and cost-effective diagnostic modality that will impact serosurveillance of mice used in research.     

Simultaneous Serodetection of 10 Highly Prevalent Mouse Infectious Pathogens in a Single Reaction by Multiplex Analysis

Under current practices of mouse colony maintenance, sera from mice are analyzed for antibodies against several widespread infectious pathogens by conventional immunoassays, generally enzyme-linked immunosorbent assay (ELISA). To test for multiple agents, these methods consume large volumes of mouse serum and are laborious and time-consuming. More efficient immunoassays, using small amounts of sample, are therefore needed. Accordingly, we have developed a novel multiplex diagnostic system that employs fluorescent microbeads, coated with purified antigens, for simultaneous serodetection of 10 mouse infectious agents. Individually identifiable, fluorescent microbeads were coated with antigens from Sendai virus, mouse hepatitis virus, Theiler's mouse encephalomyelitis virus/GDVII strain, mouse minute virus, mouse cytomegalovirus, respiratory enteric orphan virus (Reo-3 virus), mouse parvovirus, calf rotavirus for epizootic diarrhea virus of infant mice, vaccinia virus for ectromelia virus, and Mycoplasma pulmonis. Standard sera, singly positive for antibodies to individual infectious agents, were generated by inoculation of BALB/cj and C57BL/6j mice. Sera from these experimentally infected mice, as well as sera from naturally infected mice, were analyzed using a mixture of microbeads coated with antigens of the 10 infectious agents listed above. Results demonstrated that the multiplex assay was at least as sensitive and specific as ELISA for serodetection. Importantly, the multiplex assay required only 1 microliter of serum for simultaneous serodetection of the 10 mouse infectious agents in one reaction vessel. Thus, this multiplex microbead assay is a reliable, efficient, and cost-effective diagnostic modality that will impact serosurveillance of mice used in research.     

Inhibition by estrone of the antiviral protection and interferon elicited by interferon inducers in mice

The susceptibility of mice to infection with MM virus is markedly increased after treatment with the sex hormone estrone. Studies were undertaken to determine if either suppression of production or interference with the action of interferon was involved in this phenomenon. The protection of mice against MM virus infection by several interferon-inducing agents was partially impeded by estrone treatment either 24 hr before or 24 hr after the administration of the inducing agent. The titers of circulating interferon induced by each of the agents were lower in estrone-pretreated animals than in untreated controls. The protection of mice by exogenous L cell interferon was blocked only when the hormone was given prior to the interferon. It is concluded that the adverse activity of estrone is related to its ability to interfere with the action of interferon.     

Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production

OK-432, a lyophilized preparation of Streptococcus pyogenes, showed a priming activity for TNF production in mice, associated with an increase of spleen weight. PSK, a protein-bound polysaccharide preparation from Coriolus versicolor, did not show such activity. Both OK-432 and PSK potentiated the TNF production in mice primed with Corynebacterium parvum (CP) and challenged with Escherichia coli endotoxin (LPS). Cytotoxic antitumor agents of 5-fluorouracil (5-FU), cyclophosphamide (CY) and bleomycin (BLM) suppressed TNF production in mice primed with CP and challenged with LPS. TNF production suppressed by 5-FU, CY and BLM was partially restored by the combined treatment with OK-432 or PSK. These results suggest that the administration of cytotoxic antitumor agents suppresses the intrinsic TNF production in cancer patients, and the combined use of immunostimulants such as OK-432 and PSK is advantageous in restoring TNF production suppressed by cytotoxic antitumor agents.     

The effect of five antibacterial agents on the physiological levels of serum nitric oxide in mice

In addition to their action on microorganisms, antibacterial agents have been reported to affect host defense mechanisms. Nitric oxide (NO) that is produced by a number of cell types in the innate immune response is bactericidal, but when produced in excessive amounts it could be detrimental to the host. In this study, five antibacterial agents (gentamicin, tobramycin, imipenem, tigecycline, isoniazid) were compared with respect to their ability to affect NO production in mice. Groups of mice were injected with the different antibacterial agents, and at different time intervals post-injection serum NO levels were determined using the Griess reagent. All the antibacterial agents tested showed a significant effect in reducing NO levels in mice. It could be hypothesized that the excessive production of NO in infectious diseases is in most instances suppressed by the antibacterial agent(s) used.     

Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4 to 6 months after infection. The magnitude of reactivation was more pronounced in innately resistant CBA/Ca mice than in the susceptible C57BL/6 strain of mice. Splenic bacterial counts were also amplified by anti-L3T4 antibody when the antibody was injected at the chronic phase, whereas cyclosporin A had an effect only during the initial 6 weeks after BCG infection. Cultures of spleen cells from chronically infected mice showed a significant increase in the numbers of viable BCG recovered after 7 days of incubation in the presence of dexamethasone but not with cyclosporin A. The observed differences between the tested immunosuppressive agents indicate that the stationary bacterial counts during chronic BCG infection are maintained by discrete T-cell actions on the infected macrophages.