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L M Mikhaĭlova

Publications and source records attributed to L M Mikhaĭlova.

14 recordsLinked to original sources
PubMed2001

[A novel immunoregulating hexapeptide with antineoplastic effect].

A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.

Adjuvants, Immunologic↗
PubMed2001

[Preclinical toxicological study of theraphthal-Lio and binary catalytic system "theraphthal-Lio+ascorbic acid"].

Pre-clinical toxicologic studies were conducted of a new drug teraphtal-Lio (TPh) and a teraphtal-Lio + ascorbic acid (TPh + AA) catalytic system recommended for binary catalytic therapy of malignant tumors. Quantitative criteria for "acute" and "chronic" toxicity of TPh and TPh + AA were established, which describe their toxic effects in single or multiple application. The coefficient of specific sensitivity and cumulation index for TPh and TPh + AA were determined. The toxicodynamic characteristics of TPh and TPh + AA were investigated. The results were used to prognose pulmonary, cardio-vascular, hemato- and hepatotoxic as well as hemodynamic and ophthalmologic disorders and functional changes in the central nervous system involved in clinical use of TPh and TPh + AA.

Animals↗
PubMed2001

[Effects of theraphthal-Lio on hemostasis in experimental animals].

Teraphtal-Lio (Tph) exerted a toxic dose-dependent effect on the hemostatic system. Treatment of experimental animals with maximum tolerated and highly toxic doses was followed by acute DVS syndrome formation involving a hemophilic condition, soaring activated partial prothrombin time, absence of fibrinogen, sharp rise in fibrinogen degradation product and D-dimer matched by fall in thrombocyte count. No toxic influence on the hemostatic system was registered when Tph doses recommended for humans in the course of phase II clinical trials were administered to animals.

Animals↗
PubMed1996

[Inhibitors of the ADP/ATP antiporter induce two Ca2+-dependent uncoupling systems in rat liver mitochondria].

Effect of an ADP/ATP antiporter inhibitor carboxyatractylate on permeability of inner mitochondrial membrane was studied. Carboxyatractylate induced two uncoupling systems: Ca(2+)-dependent pore and another system which was sensitive to an inhibitor of calcium uniporter ruthenium red (apparently, Ca(2+)-recycle). Extent of Ca(2+)-recycle induction correlates with a fraction of mitochondrial population which underwent permeabilization; inhibition of permeabilization by cyclosporin A prevents induction of the recycle. Thus, induction of Ca(2+)-dependent pore is direct consequence of carboxyatractylate binding to mitochondria whereas induction of Ca(2+)-recycle is indirect. Both uncoupling systems are induced by carboxyatractylate concentrations which are specific for ADP/ATP antiporter. The data suggest that the antiporter can directly participate in the formation of Ca(2+)-dependent pore in inner mitochondrial membrane.

Animals↗
PubMed1995

[Low concentrations of cyclosporin A close Ca2+-dependent inner mitochondrial membrane pores in the absence of other effectors].

Earlier it has been demonstrated that the recoupling action of cyclosporin A on mitochondria deenergized by the opening of the Ca(+)-dependent pore requires higher cyclosporin A concentrations than those, which are necessary for preventing the permeabilization as well as the presence of additional effectors, such as adenine nucleotides and Mg2+. It has been shown that cyclosporin A reseals the pore and prevents its opening when used at the same low concentrations (0.1-0.4 microM), while its higher concentrations (0.5-1.0 microM) produce the recoupling of mitochondria. In contrast with recoupling, resealing of the pore by cyclosporin A does not require Mg2+ or adenine nucleotides. Carboxyatractylate which reverses the cyclosporin A-induced restoration of the membrane potential does not induce repeated opening of the pore. The carboxyatractylate-induced depolarization of the inner mitochondrial membrane is sensitive to ruthenium red. Besides, ruthenium red restores the recoupling action of cyclosporin A in the absence of carboxyatractylate. The data obtained suggest that the loss by cyclosporin A of its recoupling potency may result from the induction of the Ca2+/2H+ antiporter. Induction of the Ca2+/2H+ antiporter in combination with a ruthenium red-sensitive Ca2+ uniporter provides the uncoupling mitochondria even with a closed Ca(2+)-dependent pore. Apparently, Ca2+/2H+ antiporter induction is a result of inhibition of the ADP/ATP antiporter by a natural or exogenous inhibitor. This process seems to require a preliminary release of certain protective factors from the mitochondrial matrix.

Adenine Nucleotides↗
PubMed1994

[Closure of Ca2+-dependent pores by cyclosporin A: the role of magnesium ions, adenine nucleotides, and conformation status of the ADP/ATP antiporter].

Effects of ADP and Mg2+ on the ability of cyclosporin A to "reseal" mitochondria permeabilized by Ca2+ and P(i) have been studied. Cyclosporin A was completely ineffective, when ADP and Mg2+ were not included into the incubation medium. Both ADP and Mg2+ used at high concentrations potentiated the effect of cyclosporin A and prevented it reversal by carboxyatractylate. Data on the influence of different concentrations of ADP and Mg2+ on the resealing efficiency of cyclosporin A suggest that the true effector modulating the state of the Ca(2+)-dependent pore is the ADP-Mg2+ complex, but not ADP or Mg2+ used separately. The ability of non-hydrolyzable analogs of adenine nucleotides, ADP-S and ATP-S, to potentiate the resealing action of cyclosporin on mitochondria permeabilized by loading of different Ca2+ concentrations to that of ADP was compared. ATP-S was ineffective when the pore was induced by high concentrations of Ca2+. The results obtained are discussed in terms of hypothesis on the direct involvement of the ADP/ATP antiporter in regulation of the inner mitochondrial membrane Ca(2+)-dependent pore state.

Adenine Nucleotides↗
PubMedDate not supplied

[Toxicological properties of fentirin].

Phentyrin toxicity depends to a large measure on the route of its administration. Adequately toxic doses of phentyrin intravenously are approximately ten times as less compared to peroral administration. High doses of the drug produce appetite loss, occasional vomiting, salivation, diarrhea, flabbiness and weight loss. ECG shows slow pulse, reduced voltage and changes in T wave. At early periods the animals' death ensues with phenomena of emaciation, a delayed death can be recorded only in some cases. Morbid anatomy shows atrophic changes in the lymphatic nodes, in the spleen, thyroid, in the gastrointestinal mucosa, and changes in the liver and kidneys. Phentyrin in tolerated doses exerts no adverse action on stem cells of bone marrow, but affects spleen cells. The drug alters the weight of some endocrine organs -- the thyroid, uterus and adrenals.

Animals↗