[The leading role of mitochondrial depolarization in the mechanism of glutamate-induced disorder in Ca(2+)-homeostasis]. / Vedushchaia rol' mitokhondrial'noi depoliarizatsii v mekhanizme glutamat-vyzvannogo narusheniia Ca(2+)-gomeostaza.

Digital fluorescence imaging techniques were employed to monitor changes in the cytoplasmic Ca2+ concentration and mitochondrial potential in fura-2 AM or rhodamine-123 loaded individual cerebellar granule cells during and following the Glu exposure. The data obtained suggests that the MD-induced blockade of the mitochondrial Ca2+ uptake and a reversal of the mitochondrial ATP-synthase play a critical role in the mechanism of the glutamate-induced disorder of neuronal Ca2+ homeostasis.

[Polyradiomodification. The efficacy of the postradiation use of hyperglycemia and hyperthermia in treating tumors of different sizes]. / Poliradiomodifikatsiia. Effektivnost' postradiatsionnogo primeneniia giperglikemii i gipertermii pri lechenii opukholei raznoi velichiny.

The paper is concerned with comparative assessment of the effectiveness of the separate and combined postradiation use of induced hyperglycemia (IH) and local hyperthermia (HT) with respect to tumor size in experiments on mice with transplantable Ehrlich carcinoma. The antitumor effect of these modalities was estimated by the criteria of the duration of tumor growth inhibition and cure of animals. The combined use of IH and HT significantly enhanced antitumor action of prior irradiation and resulted in improved therapeutic results for medium- and large-size tumors as compared to small ones. The authors discussed probable causes of enhancing the effectiveness of IH and HT with tumor growth, as a result of changes in pH, blood supply and other tumor characteristics.

[Hyperglycemia as a means of increasing the efficacy of hyperthermia in radiotherapy of tumors]. / Giperglikemiia kak sredstvo povysheniia éffektivnosti gipertermii pri luchevoi terapii opukholei.

In experiments on mice with Ehrlich carcinoma transplanted into the thigh the authors determined a gain in tumor heating from the use of induced hyperglycemia (IH) during thermoradiotherapy. Tumors were irradiated at a dose of 20 Gy followed in 3 h by local hyperthermia (HT) by emerging a tumor into water at 40-45 degrees C for 30 min. IH followed irradiation (i.e. 3 h before HT) in the form of 5-time ip administration of glucose at a total dose of 10.4 g/kg for 2 h. Isoeffective tumor damage was achieved in irradiation combined with HT (45 degrees C) only and in irradiation with subsequent IH and HT (40 degrees C), i.e. a gain in the temperature of heated water as a result of glucose use was 5 degrees C. In the independent use (without irradiation) of HT this value was equal approximately 2.5 degrees C. Thermometric investigations have shown that these effects are partially accounted for by better heating (by 0.2-0.4 degrees C) of tumor tissue in IH. However glucose action was mainly connected with resultant physiological changes in tumors like a noticeable decrease in pH and stable disorder of the blood flow.

[Possibility of lowering the dose of metronidazole during the irradiation of tumors using subsequent artificial hyperglycemia]. / Vozmozhnost' snizheniia dozy metronidazola pri obluchenii opukholei sposleduiushchei iskusstvenoi giperglikemiei.

The therapeutic efficacy of a scheme of poly-radiomodification with metronidazole (MZ) administration was investigated in experiments on mice with Ehrlich carcinoma before local irradiation of tumors and with subsequent induced hyperglycemia (IH) depending on a MZ dose. For equally effective potentiation of the effect of radiation on a tumor during a combined use of MZ and postradiation IH a 4-fold lower dose of the drug was required as combined to MZ used alone. The combined effect of the modifiers was superadditive. The use of IH in this scheme not only potentiated skin radiation reactions on a tumor growth zone but also slightly weakened their expression.

[Polyradiomodification. Optimization of the combined use of hyperglycemia and local hyperthermia in tumor irradiation]. / Poliradiomodifikatsiia. Optimizatsiia sochetannogo primeneniia giperglikemii i lokal'noi gipertermii pri obluchenii opukholei.

Therapeutic potentialities of various types of polyradiomodification were compared in experiments on mice with solid Ehrlich carcinoma by using separate and combined use of short-term hyperglycemia (SH) and local hyperthermia (HT). In the combination of modifiers SH was always created 3 h after the beginning of glucose administration. Irradiation of tumors was performed in either of 5 moments: 4 h or immediately before SH, in-between SH and HT, 30 min. or 2.5 h after SH. Two control schemes, in which irradiation was combined with one of the modifiers only, corresponded to each polyradiomodification regimen. The combined use of SH and HT produced a more noticeable effect than their separate action. A maximum effect on a tumor was observed in the combined use of both modalities shortly after irradiation, and it was not accompanied by enhanced skin radiation injury in a tumor growth zone. Irradiation after or in-between SH and TH resulted in enhanced skin radiation reactions. Thus, the highest therapeutic effect was noted in those schemes of polyradiomodification in which SH and HT followed radiation treatment. SH and HT induced suppression of the blood supply in tumors played an important role in the optimization of the combined use of SH and HT with irradiation.

[The role of a decrease in pH in enhancing the antitumor action of ionizing radiation with the aid of hyperglycemia]. / Rol' snizheniia pH v usilenii protivoopukholevogo deistviia ioniziruiushchego izlucheniia s pomoshch'iu giperglikemii.

The role of a pH decrease in glucose-enhanced antitumor action of prior irradiation was investigated in experiments on mice with Ehrlich solid carcinoma. For this purpose changes in pH and the blood flow as well as the modification of a tumor radiation effect caused by glucose and weakly metabolizing galactose injected in similar regimens, were compared in parallel groups. It was shown that in both regimens glucose and galactose injections resulted in approximately the same reduction of a blood flow rate in tumors, however a pH decrease after the use of glucose was much greater, and glucose-enhanced antitumor radiation action was more noticeable. A conclusion has been made that a pH decrease in tumors is a major factor determining the efficacy of glucose as a radiomodifier.

[Polyradiomodification. Combined body protection in the total irradiation of mice during exogenous hypoxia]. / Poliradiomodifikatsiia. Kombinirovannaia zashchita organizma pri total'nom obluchenii myshei v usloviiakh ékzogennoi gipoksii.

A high efficacy of the combined use of nontoxic doses of two pharmaceuticals: cystamine (50 mg/kg) and mexamine (25 mg/kg) under the conditions of short-term exogenous hypoxia (7.5% O2) was found in (CBA X C57Bl)F1 mice. The dose modification factor using the survival rates was 2.56.

[Enhancement of the antitumor effect of ionizing radiations in the combined use of metronidazole and induced hyperglycemia]. / Usilenie protivoopukholevogo deistviia ioniziruiushchikh izluchenii pri sochetannom primenenii metronidazola i giperglikemii.

The authors have shown that a more pronounced antitumor effect of radiation in the combined use of metronidazole and induced short-term hyperglycemia (STH) may result not only from the summation of the two effects: the sensitizing effect of metronidazole and decreased viability of irradiated cells caused by STH but also from the intensified cytotoxic effect of metronidazole on hypoxic tumor cells. It was also noted that when hypoxic cells subjected to the sensitizing effect of electron acceptor sensitizers are found in the normal and tumorous tissues (skin), STH use following irradiation in the presence of metronidazole enhances selectively the tumor radiation effect.

[Combined use of radiosensitizing and protective agents in experimental radiotherapy]. / Sochetannoe primenenie radiosensibilizatorov i protektorov pri éksperimental'noi luchevoi terapii.

The appropriateness of the combined use of electron acceptor radiosensitizers: 4-nitroimidazole and metronidazole, and sulfhydryl protectors WR-2721 (gammaphos) and cysteamine was shown on the Chinese hamster cells V-79 and transplantable mouse tumors. The administration of the sensitizer 30-60 min and the protector 15-20 min before the irradiation of solid tumors weakens radiation reactions of the skin (metronidazole plus gammaphos) without weakening the effect of radiosensitization on transplantable animal tumors (metronidazole plus gammaphos or 4-nitroimidazole plus WR-2721).

[Problem of enhancing the biological action of ionizing radiation. 11. Comparative evaluation of the radiosensitizing action of metronidazole on newborn and adult mice]. / Problema uslieniia biologicheskogo deistviia ioniziruiushchikh izluchenii. Soobshchenie 11. Sravnitel'naia otsenka radiosensibilizi-ruiushchego deistviia metronidazola na novorozhdennykh i vzroslykh myshei.

The radiosensitizing effect of metronidazole is most pronounced in conditions of acute hypoxia (mature mice, 5% O2) or anoxia (neonatels, 100% N2) and decreases with increasing O2 content in a gas mixture. The preparation is less effective in neonatal mice, adapted to oxygen deficiency, than in mature animals. The data obtained are discussed with respect to the problem of overcoming the radioresistance of tumours that is conditioned by hypoxic cells.