Effect of immunosuppressors cyclophosphane and 5-fluorouracil on natural cytotoxicity and activity of lysosomal enzymes of splenocytes in C3HA mice

Effects of two immunosuppressors, cyclophosphane abd 5-fluorouracyl, used in clinical practice for treatment of oncological diseases, were assessed in respect to cytotoxicity and activity of several lysosomal enzymes located in splenocyte granules of C3HA mice. 48 h after a single intraperitoneal injection, both preparations produced a marked decrease in their cytotoxic activity, which was accompanied by a pronounced splenopathy. Both preparations were shown to decrease activity of arylsulfatase. Administration of cyclophosphane brought about the rise of activity of acid lipase as compared to control. Activities of acid phosphatase, alpha-mannosidase, beta-galactosidase, and N-acetyl-beta-D-glucosidase did not change after administration of the used immunosuppressors. It may be suggested that only arylsulfatase and acid lipase are involved in performance and(or) manifestation of the natural killer activity in splenocytes of the C3HA mice after their administration with cyclophosphane or 5-fluorouracyl.     

Action of carminomycin on leukemic cell proliferation and some problems of its use in the combined therapy of leukemias

The effect of carminomycin on the mitotic cycle of the cells of the transplantable leukemia L-1210 and the therapeutic activity of other antitumor drugs, such as phopurine and cyclophosphane was studied on mice BDF1. It was found that the cells in phases S and G2 of the mitotic cycle were most sensitive to carminomycin. Transfer G1--S and phase G1 were characterized by resistance to the antibiotic effect. When carminomycin was used in combination with phopurine or cyclophosphane, clear dependence of the therapeutic efficacy on the treatment scheme was noted. Simultaneous administration of all the three drugs resulted in potentiation of the antileukemic effect. An analogous effect was observed when carminomycin was administered prior to phopurine or cyclophosphane. When the order of the drugs use was reverse, the efficacy of the combined therapy was significantly lower than the summation antileukemic effect of the drugs.     

Effect of metronidazole and local irradiation of the tumor on paramagnetic metal complexes of the liver and tumor tissues

A study was made of changes in the intensity of the ESR signals in tissues of sarcoma-37 and liver of mice after radiation of the tumor, administration of metronidazole, and after the combined effect of the two factors. The most pronounced changes in the ESR signals were induced by metronidazole. An appreciable increase in the content of nitrosyl complexes in the tumor was noted after the combined effect of metronidazole and radiation which was indicative of the radiation-induced formation of a large number of metronidazole anion-radicals in the tumor.     

Changes in the biological properties of Mycoplasma hominis under the influence of prednisolone and cyclophosphane

The results of experimental investigations on the influence of prednisolone and cyclophosphane on biological properties of M. hominis are presented. Changes in the morphology of mycoplasmal colonies depending on the type and dose of the preparation were stated. The virulence of mycoplasmas was found to be intensified with an increase of the concentration of prednisolone in the culture medium from 0.1 to 20.0 micrograms/ml and that of cyclophosphane from 0.2 to 20.0 micrograms/ml.     

Effect of myelopeptide-1 on the functional activity of phagocytes from mice treated with cyclophosphane

The capacity of the bone marrow-derived myelopeptide-1 (MP-1) to affect in vivo and in vitro the functional activity of phagocytes of intact mice and mice treated with a cytostatic agent (cyclophosphane) has been studied. It was found that MP-1 produces a correcting effect on the functional activity of bone marrow and peripheral blood phagocytes. An optimal scheme of the injection of MP-1 to mice with the cyclophosphane-induced immunodeficiency was developed, which provides a maximum immunocorrecting action. MP-1 had the most pronounced effect on the quantitative characteristics and the functional activity of phagocytes of different localization when introduced prior to the cytostatic; under these conditions, the pep tide affects peripheral blood neutrophils. The results obtained enable one to consider MP-1 as a preparation protecting the peripheral blood phagocytes from the damaging action of cyclophosphane.     

Radiosensitizing and toxic action of metronidazole and isometronidazole (1-(2-hydroxyethyl)-2-methyl-4-nitroimidazole) on the cells of Ehrlich ascites cancer and hemoblastosis La in vitro

A study was made of Ehrlich ascites tumor growth and life span of mice bearing hemoblastosis La after inoculation of tumor cells subjected, in anaerobic conditions, to the effect of gamma-radiation and/or metronidazole and isometronidazole. It was shown that the cytotoxic effect of isometronidazole was less manifest than that of metronidazole the radiosensitizing effect, with a reference to anoxic tumor cells in vitro, being nearly the same.     

Effect of hypoxic cell sensitizer metronidazole on the radiation reaction of clonogenic cells from solid tumors

The clonogenic capacity of cells from peripheral and central zones of solid NKLy tumors of mice treated with metronidazole, a sensitizer of hypoxic cells, and with a mixture of metronidazole and radiation was studied by cloning in diffusion chambers. The cytotoxic effect of metronidazole was only noted during the prolonged interaction with cells under acute hypoxia that was observed in central tumor zones. Metronidazole increased by more than two times the radiosensitivity of cells from the central zones of the tumor and did not influence the radiation response of cells from the peripheral zones. Metronidazole was shown to inhibit the repair of potentially lethal radiation damages.     

Modification of the radiosensitizing effect of metronidazole by 5-fluorouracil and caffeine

A study was made of the combined effect of 5-fluorouracil, metronidazole, caffeine and radiation on radiosensitivity of Pliss lymphosarcoma and protein synthesis rate during the first few hours following irradiation. A complete regression of the tumor was noted in 100% of animals after a 3-fold exposure. Effective postirradiation inhibition of protein synthesis was achieved by injection of metronidazole and caffeine together with 5-fluorouracil.     

酵母多糖对S_(180)荷瘤小鼠抗氧化作用和免疫机能的影响

目的:研究酵母多糖(zymosan)对S180荷瘤小鼠抗氧化状态和免疫功能的影响。方法:将昆明小鼠70只随机分为7组,第1组作为正常组,另6组将S180瘤细胞悬液接种于小鼠右前肢腋皮下制备荷瘤小鼠动物模型,分为zymosan低、中、高剂量组和环磷酰胺(Cy)组、肿瘤对照组及zymosan联合Cy治疗组,灌胃第7 d接种S180瘤,第19 d后测定小鼠肝匀浆中丙二醛(MDA)含量、谷胱甘肽过氧化酶(GSH-Px)和超氧化物歧化酶(SOD)活力,评价zymosan对小鼠抗氧化能力的作用。采用逆转录-聚合酶链反应(RT-PCR)检测IL-2、TNF-α、TGF-β1mRNA的表达,评价zymosan对小鼠免疫功能的影响。结果:zymosan各剂量组均能提高肝脏中GSH-Px活性和SOD活力,但zymosan高剂量组显著降低MDA水平(P<0.01)。zymosan各剂量组荷瘤小鼠肿瘤组织内TNF-α、IL-2 mRNA相对表达量明显高于Cy组和肿瘤对照组(P<0.01),同时下调TGF-β1水平。zymosan高剂量对小鼠S180瘤有明显抑制作用,且与Cy合用后有协同作用,并提高了小鼠的TNF-α、IL-2 mRNA的表达。结论:zymosan的抑瘤机制可能主要是抗氧化作用和免疫调节作用,且作用与剂量有关。     

Role of lysosomes in immunodepression

Degrading of heterologous protein--bovine serum albumin--under the action of lysosomes inhibited the immunodepressive preparations with chlorophos and 2,4-dichlorphenoxyacetic acid (2,4-D). Immunodepressors (chlorophos, 2,4-D, cyclophosphane, phosphestrol, methotrexate, ftuoruracil) suppressed the activity of cathepsin, whereas dibasol--an immunostimulant--failed to alter its activity. The principal possibility of the selective immunodepression at the level of lysosome enzymes is substantiated.     

Combined effect of metronidazole, interferon synthesis inducers and DNA repair inhibitors

In experiments on mice with solid sarcoma 37, a study was made of modification of the radiosensitizing effect of metronidazole. The increase in the leucotic interferon titre, induced by the interferon synthesis inductors, did not influence the radiosensitizing efficiency of metronidazole: after the administration of the repair inhibitor, 8-bromocaffeine, the coefficient of suppression of tumor growth was higher and the number of mice with the regressed tumors greater as compared to animals affected by metronidazole and radiation.     

Modifying action of drug preparations on the effect of promutagen compounds

The Ames test has shown that the action of nitrosomorpholine and cyclophosphane promutagens on bacteria of Salmonella typhimurium TA 1950 increases while using S-9 liver fraction of rats treated with pharmaceuticals of amidopyrine, reserpine and pyrazidol and decreases while using those treated with phenazepam.     

Effect of autologous blood irradiated in isolation on the restoration of leukopoiesis in an experimental model of prolonged leukopenia

Reinfusion of irradiated (220 Gy) isolated blood (IIB) was shown to accelerate leukopoiesis restoration in conditions of myelodepression induced by the injection of cyclophosphane. Restoration of leucocyte count in the peripheral blood was preceded by the increase in DNA synthesis and bone marrow cellularity. Reinfusion of IIB also promoted a more rapid restoration of cellularity of lymphoid organs with cAMP predominating therein. The comparison of the processes under study in time permits to assume that the stimulatory effect of IIB is related to activation of proliferation and stimulation of cell maturing in bone marrow and lymphoid organs.     

Model of meningococcal sepsis in mice]

The authors studied a possibility of obtaining experimental meningococcus sepsis model on mice. The use of cyclophosphane, iron compounds, yolk medium produced no significant organism. When 4--5% mucine was injected intraperitoneally together with meningococcus culture mice died with sepsis phenomena. Differences were revealed in the sensitivity of linear and mongrel mice to meningococcus infection--AKR mice proved to be more sensitive. At the same time it was found that mongrel mice weighing from 10 to 12 g could be used to induce meningococcus sepsis.     

Study of the process of promutagen biotransformation by the Ames test. I. The role of conjugation with glutathione in the modification of the mutagenic activity of nitrosomorpholine, diethylnitrosamine and cyclophosphamide

It is demonstrated that the level of the action of nitrosomorpholine (NM), diethyl nitrosoamine (DENA) and cyclophosphane (CP) promutagens on bacteria is lowered as a result of the Ames test modification by means of addition of reduced glutathione (G-SH) to the activating mixture. The data are presented on the dependence of this phenomenon on concentration of promutagens and G-SH, the period of bacteria preincubation with the compound under study and the activating mixture as well as on concentration of microsomal protein. No changes in the mutagenic effect of NM, DENA and CP were observed when G-SH was substituted for cysteine in equimolar concentration. This fact points to enzymic mechanism involved in elimination of the damaging effect of mutagenic metabolites of the compounds studied.     

The frequency of recurrences and metastases of bladder cancer following a radical course of radiotherapy]

The authors compare the incidence of bladder carcinoma recurrences and dissemination after long-distance gamma-beam therapy, carried out according to a traditional method, and in an accelerated hyperfractionation mode combined with metronidazole therapy. The recurrences were most frequently detected at the site of the primary tumor (62-67% of cases) in 6 to 18 months after the treatment. They come to a conclusion that accelerated hyperfractionation and local metronidazole radio-modification were conducive to a reduction of the incidence of recurrences from 45 to 28% as against the traditional split radiotherapy course in the classical fractionation mode.     

Frame-shift mutations in NAD(P)H flavin oxidoreductase encoding gene (frxA) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance

Metronidazole is a critical ingredient for combination therapies of Helicobacter pylori infection, the major cause of peptic ulcer and gastric cancer. It has been recently reported that metronidazole resistance from H. pylori ATCC43504 is caused by the insertion of a mini-IS605 sequence and deletion of sequences in an oxygen insensitive NAD(P)H nitroreductase encoding gene (rdxA). We also found that an additional gene (frxA) encoding NAD(P)H flavin oxidoreductase in the same strain was truncated by frame-shift mutations. To assess whether the frxA truncation is also involved in metronidazole resistance, metronidazole sensitive H. pylori strains ATCC43629 and SS1 were transformed by the truncated frxA gene cloned from strain ATCC43504. All transformed cells grew on agar plates containing 16 microg ml(-1) of metronidazole. The involvement of the frxA gene in metronidazole resistance was also confirmed by insertion inactivation of frxA and/or rdxA genes from strain ATCC43629 and one metronidazole sensitive clinical isolate H. pylori 2600. In addition, the frxA gene cloned from the H. pylori 2600 showed metronidazole nitroreductase activity in Escherichia coli and rendered ordinary metronidazole resistant E. coli to metronidazole sensitive cell. These results indicate that the frxA gene may also be involved in metronidazole resistance among clinical H. pylori isolates.     

Effect of metronidazole on the free thymidine content in the blood serum of irradiated mice

The influence of a radiosensitizer, metronidazole, on the free thymidine content of blood serum of irradiated mice was studied in aerobic and hypoxic conditions. A heated metronidazole solution (1 mg/g) was administered intraperitoneally 30 min before irradiation of animals with a dose of 3 Gy. Thymidine concentration in blood serum was determined by the radioimmunological technique. The influence of metronidazole on the level of thymidinemia was only noted in the animals exposed under hypoxic conditions.     

Relation between immune and inflammatory reactions

Lung inflammation in Wistar rats was induced by transthoracic inoculation of live and inactivated cultures of Staphylococcus aureus P209. In the former case the rats received phitohemagglutinin and cyclophosphane. A specific nature of inflammatory processes in these conditions was confirmed by histological, histo-cytochemical and bacterioscopic indexes; humoral and cellular immune responses being similar. The data show no direct correlation between inflammatory and immune reactions.     

Assessment of susceptibility to metronidazole and vancomycin of Clostridium difficile strains isolated between 1998-2002

The drugs of choice used to treat C. diffcile associated diarrhoea (CDAD) are metronidazole and vancomycin. C. difficile strains isolated in most laboratories are susceptible to metronidazole and vancomycin. Communication about emergence of antimicrobial resistance among C. difficile strains in some countries to metronidazole and intermediate resistance to vancomycin are alarming. This study was performed to determine the susceptibility to metronidazole and vancomycin of 140 C. difficile strains isolated from patients with CDAD hospitalised in academic hospital between 1999-2002. Resistance to metronidazole and vancomycin was not observed.