The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.

Changes in Oncogene Expression in Experimental Glioblastoma 101.8 Rats during Therapy with PLGA Nanoparticles Loaded with Doxorubicin.

We compared the expression of the main glioblastoma oncogenes during therapy with doxorubicin (Dox) and Dox in nanoparticles based on a copolymer of lactic and glycolic acids (Dox-PLGA) at a delayed start of treatment. Late initiation of Dox-PLGA therapy of glioblastoma showed an increase in the expression of multiple drug resistance genes, such as Abcb1b and Mgmt, and a decrease in Sox2 expression. Increased expression of other oncogenes (Melk, Wnt3, Gdnf, and Pdgfra) were observed during both Dox and Dox-PLGA therapy. These changes indicate increased tumor aggressiveness and its resistance to cytostatics at the late start of therapy.

[Toxicological Evaluation of Intravenous Formulation of Rifapentine.]

Rifapentine belongs to the most potent antituberculosis drugs. Nevertheless, there are some limitations for its clinical use because of the low aqueous solubility and side effects. A technological approach to development of rifapentine intravenous formulation based on human serum albumin was described earlier and its efficacy against experimental tuberculosis was estimated. Toxicological evaluation of that water-compatible form of rifapentine revealed its low acute toxicity (LD50 340 mg/kg). Chronic toxicity tests of both the oral substance and the injectable formulation of rifapentine demonstrated similar adverse effects. However, in contrast to the conventional oral formulations, the intravenous formulation of rifapentine had no gastrointestinal toxic effects or cardiotoxicity, thus suggesting its usefulness for clinical application.

[The functional asymmetry of the olfactory control of visceral functions]. / Funktsional'naia asimmetriia ol'faktornogo kontrolia vistseral'nykh funktsii.

In amphibia (frogs) and mammals (rats, guinea pigs, cats), unilateral electrical stimulation of olfactory lobes or section of olfactory tracts resulted in considerable functional changes in respiratory and cardiovascular systems, the olfactory influences being functionally asymmetric. Possible interactions of asymmetric influences at the level of truncal visceral centers, are discussed.

[Neurons of the enteral portion of the metasympathetic system cultured in diffusion chambers]. / Issledovanie neironov énteral'noi chasti metasimpaticheskoi sistemy pri kul'tivirovanii v diffuzionnykh kamerakh.

A culture of the neurons of metasympathetic system's enteral portion of 3-5-day old rats was obtained and fragments of the mienteral plexus were implanted to adult rats-recipients. A technique of cultivation was developed for in vivo microscopy of culture's neurons. Migration of neuroblasts from the deplantate area was revealed as well as the specific features of neurons differentiation. The neurons were shown to acquire characteristic morphological features corresponding to Dogel's I and II types of neurons; growth of neurites was shown to aid to formation of neuropil and microglia. Histochemical analysis revealed a product of response to cholinesterase which is the index of formation of the acetylcholine hydrolysis system in the culture's I type neurons. The technique of electron-microscopic scanning enables to watch in detail the process of formation of interneuronal connections and formation of a synapse.