Monooxygenase System and NO Metabolism in Liver Microsomes of Rats with Toxic Hepatitis and the Effect of Sesquiterpene Lactones.

We analyzed changes in activities of enzymes of phases I and II of xenobiotic biotransformation and parameters of NO metabolism in liver microsomes of rats with toxic CCl4-induced hepatitis after a 14-day course of sesquiterpene lactones from Artemisia leucodes (10 mg/kg). It was found that toxic hepatitis was associated with significant inhibition of NADPH-cytochrome c-reductase, benzo(a)pyrene hydroxylase, and NADPH-diaphorase, reduced cytochrome P-450 content, and enhanced induction of nitrate/nitrite reductase with accumulation of NO metabolites in the liver. Administration of sesquiterpene lactones stimulated activity of the studied components of the cytochrome P-450 system and promoted recovery of the NOergic system components; the effects were most pronounced in 7 and 14 days after treatment.

Experimental Study of Yeast RNA Preparation as a Possible Radioprotective Agent for Radiotherapy of Malignant Tumors.

We studied radioprotective effects of a preparation based on yeast RNA and its influence on therapeutic efficiency of ionizing radiation against transplanted tumors. Parenteral administration of yeast RNA preparation to mice in a dose of 10 mg 1 h prior to exposure to ionizing γ-radiation (137Cs) in a lethal dose (LD80/30) increased 30-day survival by 66%; by day 80, 80% of animals survived (vs. 2.5% in the control). Whole-body exposure to ionizing γ-radiation in a dose of 7 Gy significantly increased the mean lifespan of mice with experimental lung metastases or intraperitoneally transplanted leukemia L-1210 by 42 and 20.8%, respectively. RNA preparation injected to the mice with tumors 1 h before irradiation did not affect the therapeutic efficiency of ionizing radiation or significantly potentiated it (in mice with transplanted leukemia L-1210). These results suggest that yeast RNA preparation protects healthy tissues during radiotherapy of malignant tumors.

Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.

Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

Different Efficiency of Liposomal Forms with Hydrophilic and Hydrophobic Antitumor Agents in Relation to Solid Transplants of Mouse Tumor and Its Metastases in the Liver.

Experiments were performed on the model of transplanted mouse tumor with high incidence of liver metastases. Hydrophilic drug cycloplatam (injected intravenously in liposomes) was more potent than "free cycloplatam" (injected intravenously or intraperitoneally in physiological saline) in inhibiting the growth of natural and experimental metastases in the liver. By contrast, liposomal cycloplatam had lower efficiency than free cycloplatam in suppressing the growth of solid tumor. Liposomal and free cortifen (hydrophobic hormonal cytostatic) produced nearly the same effects on solid tumor growth. Our results suggest that liposomal forms of hydrophobic compounds producing nonselective effect on tumor cells (e.g., actinomycin D or Cosmegen), should not have advantages over free forms.

Bioimpedancemetry in the diagnostics of inflammatory process in the mammary gland.

The changes in mammary gland bioimpedance were examined in the dynamics of the inflammatory process. Bioimpedance of affected gland was 2-3-fold lower than that of the contralateral one; normally, this difference did not exceed 10%. The phases of inflammation development were paralleled by changes in bioimpedance. During wound epithelization, impedance increased and approximated the normal level. Further increase of bioimpedance by more than 30% and its stabilization at this level attested to recurrence of inflammation, while its irreversible drop indicated devitalization the tissues. The diagnostic criterion attesting to the development of local inflammatory reaction is deviation of bioimpedance in the impaired area by more than 15% from that of the adjacent intact site.

Effect of low-choline diet and ethanol on electroconductivity of tissues in CBA mice.

We studied electrophysiological parameters and morphological changes in the adrenal glands and spleen of CBA mice feeding a low-choline diet and/or ethanol-containing diet. The polarization coefficient underwent similar changes in the adrenal glands and spleen, which was associated with different contribution of impedance frequency components. Morphological changes in the adrenal glands were more pronounced than in the spleen and consisted in delipidation of the adrenocortical cell cytoplasm in the zona fasciculata and increase in cell heterogeneity in the zona reticularis of animals of different groups. The observed morphological and electrophysiological changes can serve as a criterion of the severity of stress. The method for a quantitative study of tissue electroconductivity is informative for evaluation of the effects of internal and external factors on organs and tissues.