[Distribution of beta-carotene in the rat upon its intraperitoneal administration in water soluble and oil forms]. / Raspredelenie beta-karotina v organizme krys pri ego vnutribriushinnom vvedenii v vide vodorastvorimoi i maslianoi form.

Accumulation and excretion of beta-carotene in rat liver tissue were studied when the carotinoid was intraperitoneally administered as olive oil as suspension and a water liposomal suspension. Single injection of the liposomal form of beta-carotene caused an increase in its content in liver tissue. If beta-carotene was administered at a dose of 10 mg/kg its maximal content 44 mg/g of the tissue was observed within one day, and at a dose of 50 mg/kg, its maximal content constituted 178 mg/g within two days. Administration of beta-carotene as an oil suspension at a dose of 50 mg/kg led to a considerably slight accumulation in rat liver tissue with the maximal value of 12 mg/kg of the tissue within two days. Possible use of beta-carotene various forms, as well as experimental models for study their biological activity are discussed.

[Mechanism of formation of malonic dialdehyde during liposome interaction with cells]. / K mekhanizmu obrazovaniia malonovogo dial'degida pri vzaimodeistvii liposom s kletkami.

In the presence of intact Ehrlich ascite carcinoma cells and the supernatant obtained by preincubation and subsequent precipitation of cells, egg phosphatidylcholine is oxidized in liposomes to form malonic dialdehyde (MDA). Catalase and carbon dioxide markedly reduce, whereas sodium azide increases MDA accumulation during liposome incubation with the cells. EDTA, diethylthiocarbonate and alpha-tocopherol effectively inhibit, whereas ascorbate and cysteine strongly activate MDA synthesis in both cases. Superoxide dismutase has no appreciable effect on these processes. It is concluded that metal-containing catalysts and the H2O2 released by intact cells into the incubation medium induce lipid peroxidation in liposomes.

[Characteristics of interferon production from the enteral administration of inducers]. / Osobennosti produktsii interferona pri énteral'nom vvedenii induktorov.

When interferon inducers are administered to animals, autonomous local production of interferon by organs (intestine, liver) occurs alongside with the production of serum interferon. After oral administration of a low molecular interferon inducer, tilorone, the intestine is the main site of interferon synthesis. Here the peak of interferon production precedes that in the serum by 20 hours and exceeds it 16-fold. The sequence of events follows the scheme: intestine--liver--serum. Upon oral administration of high molecular inducers incorporated into liposomes (polyguacyl, lafarin) the predominant site of interferon production is the liver where over 80% of the administered inducer is localized and interferon production is 2-4-fold higher than in the intestine. The sequence of events follows the scheme: liver--intestine--serum.

[Interferon-inducing activity of liposome-incorporated double-stranded polynucleotides and the means for its enhancement]. / Interferonindutsiruiushchaia aktivnost' zakliuchennykh v liposomy dvuspiral'nykh polinukleotidov i puti ee povysheniia.

Natural double-stranded RNA (dsRNA) incorporated into liposomes upon parenteral inoculation induces 4 times as much amounts of interferon as inoculation of the equal amount of dsRNA without liposomes. Oral administration of liposome-incorporated dsRNA induces in animals serum interferon in amounts similar to those induced by parenteral inoculation of dsRNA without liposomes (320-640 units/ml). When liposome-incorporated dsRNA is used, interferon induction is prolonged to 24 hours. The prolongation period increases to 5 days after preliminary treatment of animals with "empty" liposomes. In M-19 cell culture, 2-hour treatment with liposome-incorporated dsRNA in a dose of 5-10 micrograms/ml induces a yield of 640-1280 units/ml interferon and 100% antiviral effect. The L-929 culture is more sensitive to dsRNA in liposomes. Even its minimal amounts (0.1-1 microgram/ml) after 2-3-hour contact produce a 100% antiviral effect in the presence of low amounts of interferon in the culture fluid (20-40 units/ml) or in its complete absence.

[Effect of radiomodifiers on lipid peroxidation and the structural-functional state of irradiated mitochondria]. / Vliianie radiomodifikatorov na perekisnoe okislenie lipidov i strukturno-funktsional'noe sostoianie obluchennykh mitokhondrii.

SH-Containing radioprotective agents, for instance, cysteine, cystamine, dithiothreitol, exert an antioxidant effect on gamma-radiation-induced lipid peroxidation in mitochondrial membranes and, concurrently, uncouple oxidation from phosphorylation. A radiosensitizer, N-ethylmaleimide, on the contrary, being a pro-oxidant of lipid peroxidation couples oxidation and phosphorylation. At the same time, changes in the lipid peroxidation system and in the energy production processes, observed after irradiation of a mitochondrion suspension containing modifiers, are accompanied by the increased destruction of mitochondrial membranes as compared to irradiated controls.

[Changes in the SH-group level and respiration during gamma- and Fe2+-induced lipid peroxidation in Ehrlich ascites carcinoma cells]. / Izmenenie soderzhaniia SH-grupp i dykhaniia v protsesse gamma- i Fe2+-indutsirovannogo perekisnogo okisleniia lipidov v kletkakh astsitnoi kartsinomy Erlikha.

In experiments on Ehrlich ascites tumor cells it was shown that lipid peroxidation induced by gamma-rays and Fe2+ ions was accompanied by a decrease in the endogenous SH-group content at early times after exposure (during 3-hour incubation). It was also established that no significant changes occurred in the oxygen uptake by Ehrlich ascites tumor cells depending on radiation dose of Fe2+ ion concentration. If cells were pre-kept under hypotonic conditions an additional decrease in cell respiration and SH-group content and activation of lipid peroxidation was noted.

[Interferon induction via peroral administration of high-molecular polynucleotides]. / Induktsiia interferona pri peroral'nym vvedenii vysokomolekuliarnykh polinukleotidov.

High molecular polynucleotides, poly(I).poly(C) and poly(G).poly(C), incorporated into liposomes may be used for serum interferon induction when administered orally. Titres of interferon induced by this method are sufficiently high (320-640 units/ml) and close to those induced by the same preparations administered parenterally (640-1280 units/ml). The use of liposomal polynucleotides results in prolonged (up to 24 hours) circulation of interferon in the blood of mice at a sufficiently high level. Liposomal polynucleotides are low-toxic upon oral intake. The liposome-polynucleotide complex is sufficiently stable on storage, and retains the interferon-inducing activity, if given orally, after 6 months of storage at 4 degrees C in the liquid form.

[Effect of gamma-irradiation on malonic dialdehyde formation in the interaction of liposomes with cells]. / Vliianie gamma-oblucheniia na obrazovanie malonovogo dial'degida pri vzaimodeistvii liposom s kletkami.

A study was made of the effect of relatively low gamma-radiation doses (up to 10 Gy) on the ability of Ehrlich ascites tumor cells to induce peroxidation in lipids of liposomes from egg lecithin. The mechanism of this peroxidation is probably associated with the release from cells of catalyzers which perform free-radical oxidation of higher unsaturated fatty acids. Two processes occur upon irradiation of cells: disintegration of the released catalyzers, and stimulation of their release from cells. Correspondingly, the formation of malonic dialdehyde was inhibited or stimulated depending on the radiation dose and time of the combined incubation of liposomes and cells. On the basis of the data obtained a conclusion is made that the modification of the effect of malonic dialdehyde formation upon oxidation of liposomes by the exposed cells is conditioned by the effect of radiation on cell membranes.

[Liposome transport as a model of substance absorption in the small intestine studied by electron microscopic autoradiography and scanning microscopy]. / Issledovanie transporta liposom v kachestve modeli vsasyvaniia veshchestv v tonkoi kishke metodom élektronno-mikroskopicheskoi avtoradiografii i skaniruiushchei mikroskopii.

Using electron microscope autoradiography and scanning microscopy, evidence was provided on the space-time character of the transport of enterally introduced liposomes containing 125I-lecitin and 3H-cholesterine. Liposomes underwent degradation on the mucous surface of the epithelial cells, followed by the appearance of monolayer vesicles to be transported to the glycocalix area between the microvilli. This is accompanied with the release of the radioactive trait from liposomes and its transporting to enterocytes.

[Transport of 125I-poly I : poly C incorporated in liposomes from the enteric cavity to the small intestine mucosa. An electron microscopic autoradiographic study]. / Transport 125I-poliI : poliTs, zakliuchennogo v liposomy, iz énteral'noi sredy v slizistuiu tonkoi kishki. Issledovanie metodom élektronno-mikroskopicheskoi avtoradiografii.

Transport of 125I-poly(I) : poly(C) incorporated into liposomes trough the small intestine mucose was investigated by electron microscopic autoradiography. With the migration of liposomes into the mucous layer on the luminal surface of the intestine up to the glycocalix level of microvilli these undergo degradation with the formation of monolayer liposomes from which polynucleotide is released. Later on the poly(I) : poly(C) or its fragments transported through the enterocytes to be accumulated in cells of the connective tissue stroma of the small intestine mucose. Part of polynucleotide was incorporated up to the arterial and lymphoid capillary level. Apparently, on the way of its transport the polynucleotide is affected by pancreatic and tissue nucleases. The accumulation of polynucleotide in macrophages, fibroblasts, lymphocytes, plasma cells and smooth muscle cells was traced. It is supposed that the polynucleotide accumulated in stroma of the small intestine mucose may preserve its interferon inducing activity.

[Effect of lipid peroxidation on DNA synthesis in Ehrlich ascites carcinoma cells]. / Vliianie perekisnogo okisleniia lipidov na sintez DNK v kletkakh astsitnoi kartsinomy Erlikha.

The effect of lipid peroxidation (LPO) induced by Fe2+ and linoleic acid hydroperoxides in intact cells on the rate of DNA synthesis was investigated. It was found that intensification of LPO is accompanied by a decrease of DNA synthesis rate. Under effects of linoleic acid hydroperoxides, the repression of DNA synthesis is enhanced.

[Effect of combined exposure to an interferon inducer, irradiation and 5-fluorouracil on sarcoma 37 in mice]. / Effekt kombinirovannogo vozdeistviia induktora interferona, oblucheniia i 5-ftoruratsila na sarkomu 37 myshei.

Oral administration of a liposome-encapsulated agent triggering the synthesis of interferon--poly(I) poly (C)--to mice bearing solid sarcoma 37 was followed by (a) production of an interferon which circulates for a longer period after preliminary administration of "empty" liposomes; (b) lengthening of the period of tumor latency; in some cases tumor failed to appear at all; (c) higher efficacy of radiation treatment which was manifested by a higher inhibition of tumor growth or complete regression; (d) increased antitumor effect of 5-fluorouracil, and (e) suppression of proliferative activity of tumor.

[Effect of Fe2+- and gamma-induced lipid peroxidation on respiration and oxidative phosphorylation in the mitochondria]. / Vliianie Fe2 - i gamma-indutsirovannogo perekisnogo okisleniia lipidov na dykhanie i okislitel'noe fosforilirovanie v mitokhondriiakh.

Lipid peroxidation activated by low concentrations of Fe2+ ions in a medium (1-5 microM) and gamma-quanta (10-50 Gy) stimulates the oxygen consumption and oxidative phosphorylation during the initial period of incubation (10-20 min). With relatively high concentrations of Fe2+ ions and higher radiation doses (50-100 Gy) inhibition of the activity of mitochondria is registered with respect to both indices.

[Formation of malondialdehyde during liposome interaction with cells]. / Obrazovanie malonovogo dial'degida pri vzaimodeistvii liposom s kletkami.

When AKE cells and leukocytes interact with egg lecithin liposomes malone dialdehyde (MDA) is formed and accumulated in the incubation medium. When synthetic dipalmitoyl--lecithin is used and at heat or hypotonic cell damage the rate of MDA accumulation abruptly decreases. The maximal rate of MDA accumulation in case of natural lecithin is (1.25 +/- 0.05) . 10(-15) mole of MDA per cell/hour. It is suggested that the sources of MDA are higher unsaturated fat acids of natural liposomal lipids, whose oxidation is performed by intact cells, possibly with the participation of active forms of oxygen.

[Relationship between lipid peroxide oxidation and cell respiration]. / Sviaz' perekisnogo okisleniia lipidov i kletochnogo dykhaniia.

A relationship between lipid peroxide oxidation (LPO) in biomembranes and kinetics of oxygen uptake by intact cells and cells under hypotonic shock in the course of their incubation has been studied. Different effect of bivalent ferrum ions--activators of LPO was found; it depended on cell integrity. In the cells under normal physiological conditions the rate of oxygen uptake was independent of the amount of LPO products, while in the cells placed into hypotonic medium it decreased on the background of LPO intensification as compared to the normal one. Peculiar effects of the LPO products on intact cells seem to be related to spatial disconnection of respiratory centres and to localization of peroxide oxidation reactions.