[Influence of prodigiozan-dependent comuton on the resistance of liver mitochondria against damage by protonofor].

An effector of tissue stress of hepatocytes, prodigiozan-dependent comuton (PDC), provokes deenergiezation of liver mitochondria, preloaded by Ca2+ ions. In this case a decrease of membrane potential (MP) and Ca2+ efflux by cyclosporine A sensitive mechanism of megapore is observed. If megapore is blocked by cyclosporin A, protonofor FCCP provoked decrease of MP and Ca2+ efflux by cyclosporin A-insensitive mechanism. It is shown that PDC increases resistance of mitochondria to mentioned protonofor action by inhibition of both these effects. An inhibitory action of PDC is realized by K+ and NADH-dependent mechanism. The effector of hepatocyte tissue stress, prodigiozan-dependent comuton (PDC), evokes deenergizing liver mitochondria preloaded with Ca2+, both membrane potential (MP) decrease and Ca2+ release in according to cyclosporine A-sensitive mechanism of megapore being observed. If megapore is blocked by cyclosporin A, protonophore FCCP reduces of MP and Ca2+ release in according to cyclosporin A-insensitive mechanism. PDC is shown to increase the resistance of mitochondria against protonophore action mentioned above by means of inhibition of both these effects. Inhibitory action of PDC is realized due to both K+ and NADH-dependent mechanism. Protective effect takes place only in intact mitochondria of these cells providig (on condition that) its megapore mechanism is not activated. Moreover, the results obtained are evidence of PDC can function as protector due to intensification of energy generation in damaged.

[Intraorganic and intratissue mechanisms of protective action of activated Kupffer cells on hepatocytes].

Endotoxine activated Kupfer cells release into the intercellular space several mediators which act directly on hepatocytes as well as via stellet cells. In both cases Kupfer cells downregulate hepatocytes as a part of paracrine system. However, downregulated part of liver parenchyma might be extended by several mechanisms. The first one is release of vasoconstrictors from activated Kupfer cells which stimulate stellet cells contraction. This effect may also be achieved by formation of hypermetabolicfocuses by Kupffer cells mediators with further activation of hepatocyte-hepatocyte interactions based on the principle of cell competition for oxygen in the intercellular space. Regulatory influence of activated Kupfer cells may be spread in liver parenchyma with participation of the mechanism of intratissue hepatocyte-hepatocyte interactions which also realize tissue stress reaction.

Activity of neutrophil ß-glucuronidase in diabetic and nondiabetic patients with chronic generalized periodontitis and healthy subjects.

OBJECTIVE. The aim of the study was to establish the dynamics of ß-glucuronidase activity in subjects suffering from type 1 diabetes and chronic untreated generalized periodontitis, subjects suffering from chronic untreated generalized periodontitis only, and control subjects not suffering from generic diseases with healthy periodontal tissue. MATERIAL AND METHODS. The study involved 165 19-50-year-old subjects who were divided into three groups: healthy subjects (n=55), subjects with chronic untreated generalized periodontitis (n=55), and subjects with type 1 diabetes and chronic untreated generalized periodontitis (n=55). Neutrophilic leukocytes of peripheral venous blood were exposed to bacterial stimuli: opsonized zymosan, nonopsonized Staphylococcus aureus, and prodigiosan. The activity of ß-glucuronidase was determined by the spectrofluorimetry method. RESULTS. The diagnostic value of changes in ß-glucuronidase activity of neutrophilic leukocytes markedly increased in all study groups after stimulation of neutrophilic leukocytes by opsonized zymosan, nonopsonized Staphylococcus aureus, and prodigiosan as compared to control media not exposed to any stimulus (P<0.001). The strongest relationship (canonical correlation coefficient eta, 0.993) between the intensity of periodontal pathology markers and the activity of ß-glucuronidase of neutrophilic leukocytes in incubated media in patients with type 1 diabetes mellitus and periodontitis was found under the effect of nonopsonized Staphylococcus aureus. CONCLUSIONS. If periodontal impairment is severe, diabetes mellitus possibly causes a faster destruction of the periodontal tissue and presents a higher risk of periodontitis for patients with diabetes.

The response of peripheral blood neutrophils unstimulated and stimulated by prodigiosan to smoking.

UNLABELLED: Alterations of neutrophils function by tobacco products may play a central role in the pathogenesis of periodontal diseases and several smoking related systemic diseases. The aim of the study was to assess a response of peripheral blood neutrophils unstimulated and stimulated by prodigiosan to smoking. MATERIALS AND METHODS: The study included 17 smoking men that addressed for treatment of various odontological problems to out patient department of Kaunas University Clinic. The subjects were 22-43 years of age and systemic diseases free. All subjects answered to questions about smoking habits. To assess the response of neutrophils (unstimulated and stimulated by prodigiosan) to smoking the chemiluminescence and nitroblue tetrazolium test were used to measure their oxidative metabolism. RESULTS: After smoking both neutrophils unstimulated and stimulated with prodigiosan showed considerable extracellular chemiluminescence responses, but the first one reached maximal value in 45 min, while the second one in 15 min after smoking. There was no total (intra and extracellular) chemiluminescence response of neutrophils unstimulated and stimulated by prodigiosan to smoking. Neutrophils exposed to smoking showed a significant increase in their nitroblue tetrazolium reduction. CONCLUSION: Both stimulated by prodigiosan and unstimulated peripheral blood neutrophils release reactive oxygen species extracellulary which may alter the pathogenic processes in periodontal and other systemic diseases.

[The effect of prodigiozan on the postradiational recovery of hemopoiesis in long-term bone morrow cultures of mice of different genotypes].

The influence of prodigiozan on the processes of postirradiation recovery of hemopoiesis in long-term bone morrow cultures of two strain mice, having genetic distinctions in the condition of systems of the reparation DNA was investigated. It was showh, that the irradiation of long-term bone morrow cultures of mice reparation-defective strain 101/H resulted in the greater degree damage of early haemopoietic precursors (GM-CFC), reduction of the amount of the immature and of the mature granulocytes and of the decrease of the number of stromall cells in the comparison with the bone morrow of reparation-capable mice (CBA x C57B1)F1. Under the introduction in cultures of prodigiozan for 24 hours prior to an radiation the distinctions of the speed of postirradiation recovery of hemopoiesis substantially smoothed out, and the protective effect of the drag in bone morrow cultures of mice 101/H was comparable to those, marked in bone morrow cultures of reparation-capable strain mice (CBA x C57B1)F1. It is supposed, that this effect can be caused by the activation of the hematopoietic microenvironment cellular elements and inclusion of the mechanisms of intercellular of interactions, which provide stimulation of the regenerative processes at action radioprotective drags and can in the certain degree to compensate the defect of the systems of the reparation DNA.

[The role of hematopoietic microenvironment in prodigiozan' mechanism of action on postradiation recovery of hemopoiesis in long-term bone marrow cultures]. / Rol' gemopoézindutsiruiushchego mikrookruzheniia v mekhanizme deistviia prodigiozana na protsessy postradiatsionnogo vosstanovleniia krovetvoreniia v dlitel'nykh kul'turakh kostnogo mozga.

Influence of prodigiozan in different concentrations on the process of postirradiation recovery of haemopoietic precursors (GM-CFC) and morphologically recognizable elements of the bone marrow were studied in long-term bone marrow cultures during 28 days after 2 Gy gamma-irradiation. Also, prodigiozan was studied for action on the contents of GM-CFC and induction of GM-CSF three, 24 and 48 hours after injection in cultures unexposed to radiation. It is shown that injection of prodigiozan in concentration 0.1-1.0 microg/ml 24 hours prior to irradiation stimulates postradiation recovery of GM-CFC number and a total number of myelocaryocytes in irradiation of long-term bone marrow cultures. In saved cultures there was an increase in the number of stromal cells 1 and 2 days after radiation. In non-exposed to radiation long-term bone marrow cultures injection of prodigiozan increased induction of GM-CSF and raised contents of GM-CFC. The maximal increase occurred 24 hours after introduction of radioprotector. It is suggested that one of the mechanisms of a radioprotective action of prodigiozan may be stimulation of hematopoietic microenvironment cellular elements leading to a marked release of GM-CSF or/and other cytokines and stimulation of recovery of hemopoietic precursors.

[Effect of stimulation and inhibition of macrophage functions on hypercholesterolemia in rats]. / Vliianie stimuliatsii i ingibirovaniia funktsii makrofagov na razvitie giperkholesterinemii u krys.

In this study we investigated the effects of zymosan and prodigiozan, the macrophage stimulators, and GdCl3, a macrophage inhibitor, on blood lipoprotein composition, activities of liver cholesterly ester (CE) metabolising enzymes, incorporation of [14C]cholesterol (C) into bile acids and accumulation and synthesis of CE in peritoneal macrophages (PM) of rats fed with C-enriched diet for 7 days. The increase of number of phagocyte cells quantity in liver and blood colony-stimulating activity in rats pretreated with intravenous injection of zymosan and prodigiozan was accompanied by reduced C content in blood low density and very low density lipoproteins (LDL and VLDL), increase of liver lysosomal CE hydrolase activity (without change of acyl-CoA:C acyltransferase and cytoplasmatic CE hydrolase activities) and incorporation of labeled C into bile acids and decrease of CE formation and accumulation in PM in rats with hypercholesterolemia. In contrast, reduction of phagocyte population in liver caused by intravenous injection of GdCl3 was accompanied by enhancement of C and CE level in blood LDL and VLDL and decrease of lysosomal CE hydrolase activity and incorporation of C into bile acids in liver of C-feeding rats. The data obtained suggest that the stimulation of mononuclear phagocyte system may lead to a decrease of plasma C via activation of LDL and VLDL catabolism and induction of bile acid synthesis in liver.

Liver resistance to CCl(4)-induced injury after stimulation of macrophages with various preparations.

Acute toxic hepatitis in male Wistar rats was produced by single injection of 40% CCl(4) (0.2 ml per 100 g body weight in oil). Pretreatment with various immunostimulators (bacterial polysaccharides prodigiozan and salmozan; yeast polysaccharides zymosan, peptidoglycan, and mannan; and hydrolytic enzyme egg lysozyme) produced a hepatoprotective effect correlating which the stimulatory influence on macrophages and increasing in the following order: mannan

[The cellular and humoral mechanisms of the radioprotective action of prodigiozan and indometofen on long-term mouse bone marrow cultures]. / Issledovanie kletochnykh i gumoral'nykh mekhanizmov radiozashchitnogo deistviia prodigiozana i indometofena na dlitel'nykh kul'turakh kostnogo mozga myshei.

Effects of prodigiosan and indometophen on the contents and proliferative activity of CFU and CFU-GM as well as GM-CSF prior to radiation were studied in long-term cultures of murine bone marrow. 24 hours and 5 days after administration of prodigiosan and indometophen, respectively, the long-term cultures were exposed to ionising radiation in a dose 2.0 Gy. Then, postradiation restoration of early hemopoietic cells-precursors was assessed. In unradiated cultures 24 hours after prodigiosan administration content of CFU, CFU-GM and GM-CSF increased. Indometophen administration induced unstable changes in the number of CFU and CFU-GM, elevation of GM-CSF within 1-14 days, stimulation of CFU proliferative activity within 24 hours, inhibition of CFU-HM proliferation in 1 and 6 days. After radiation, in prodigiosan- and indometophen-defended cultures radiation damage declined while postradiation recovery of CFU, CFU-GM and total number of myelokaryocytes was more active.

[The effect of stimulants of the mononuclear phagocytosing system on protein synthesis in rat organs and tissues]. / Vliianie stimuliatorov mononuklearnoi fagotsitiruiushchei sistemy na biosintez belka v organakh i tkaniakh krys.

It has been demonstrated in rat experiments that stimulation of the mononuclear phagocytizing system with a polysaccharide intensifies protein biosynthesis in various organs and tissues. In administration of high-polymer RNA into the organism increase of protein synthesis was encountered only in immunocompetent and blood-forming tissues. It is concluded that a stimulating effect in relation to macrophages is characteristic of high-polymer compounds which are absorbed by them due to receptor mediated endocytosis. The differences in the receptor apparatus of the resident macrophages determine the discovered difference in the intensification of protein biosynthesis in the organs and tissues of rats.

[The role of the mononuclear phagocyte system in regulating protein biosynthesis in rat organs and tissues in ontogeny]. / Rol' sistemy mononuklearnykh fagotsitov v reguliatsii biosinteza belka v organakh i tkaniakh krys v ontogeneze.

In experiments on Wistar rats, we demonstrate that activation of mononuclear phagocytes by a lipopolysaccharide (prodigiosin) results in a marked increase of protein biosynthesis in various organs and tissues. This control mechanism is most distinct in mature rats and undergoes involution in older rats. Cell elements in the mononuclear phagocytes (resident macrophages) originate from the bone marrow. Decrease in the reserve capacity of the bone marrow with age in response to prodigiosin administration suggests an important role of this mechanism during aging.

[Stimulation of regenerative processes and correction of the functional activity of the liver in its partial resection and toxic lesions]. / Stimuliatsiia protsessov regeneratsii i korrektsiia funktsional'noi aktivnosti pecheni pri ee chastichnoi rezektsii i toksicheskikh porazheniiakh.

The effects of hepatotropic growth factors (HGFs) and phospholipid drugs on the recovery of functions and the regeneration of the rat liver were studied in CC14-induced toxic damage and after partial hepatectomy (PHE). HGFs isolated from the cytoplasmic cells of the regenerating liver, as well as from the liver of the animals given prodigiozan and from the media taken after culturing the explants of the regenerating liver were found to stimulate DNA synthesis and hepatocytic proliferation following PHE and in the cirrhotic liver. Prodigiozan was shown to induce the formation of HGFs not only in the rat liver following PHE, but in the liver of intact animals. It was established that the covalently binding complex of albumin and bilirubin stimulated the synthesis of proteins and DNA in the regenerating liver, but non-covalently binding complex inhibited these processes. When CC14 was administered to the animals, the two complexes enhanced the reparative synthesis of DNA, without changing the level of replicating synthesis, the non-covalently binding complex completely eliminating the single-strand breaks in DNA. Phospholipid agents containing soybean and sunflower phosphatidylcholines increased the synthesis of RNA and albumin, which were decreased due to exposure to CC14 and had the property of stimulating the synthesis of total DNA and considerably enhancing that of mitochondrial DNA.

[The effect of the prodigiozan stimulation of Kupffer cells on the development of perisinusoidal fibrosis in experimental hypervitaminosis A]. / Vliianie stimulirovaniia kletok Kupfera prodigiozanom na razvitie perisinusoidal'nogo fibroza pri éksperimental'nom gipervitaminoze A.

Perisinusoidal fibrosis development in experimental hypervitaminosis A and its combination with preliminary Kupffer cells stimulation with prodigiozan was studied in rat liver using light and electron microscopy. Reticular fibers volume density naturally growing after administration of large dozes of vitamin A, significantly reduces in appropriate terms of experiment after Kupffer cells stimulation with prodigiozan. Two cell type were distinguished in perisinusoidal space: typical fat-accumulating ones and fibroblast-like ones topographically closely connected with reticuline fibres. Endotheliocytes and Kupffer cells acquire dystrophic changes in prodigiozan introduction and hypervitaminosis A combination.

[Prodigiozan modulation of the specific activity of antidepressants]. / Moduliatsiia prodigiozanom spetsificheskoi aktivnosti antidepressantov.

The experiments carried out on mongrel male mice showed that bacterial lipopolysaccharide Prodigiozan inhibit the activity of P-450-dependent monooxygenases of the liver, thus changing the activity of antidepressants--amitriptyline and imipraminum. The data on biological activity were tested in "tail suspension" test. Prodigiozan exhibited no central effect. Changes in biotransformation processes after single administration of both drugs resulted in the delay and prolongation of the effect. Prodigiozan prevents the induction of microsomal enzymes caused by antidepressants. Amitriptyline do not affect the immunostimulating action of prodigiozan, whereas imipraminum inhibited prodigiozan activity.

[The effect of pyrimidines, levamisole and prodigiozan on the antigen-specific regulation of delayed hypersensitivity in relation to the age and strain of the mice]. / Vliianie pririmidinov, levamizola i prodigiozana na antigenspetsificheskuiu reguliatsiiu giperchuvstvitel'nosti zamedlennogo tipa v zavisimosti ot vozrasta i linii myshei.

The effect of pyrimidine, levamizol, and prodigiozan on the retarded hypersensitivity (RH) was studied on a model of adoptive transfer of the splenocytes from donors of different ages to young syngeneic recipients. Splenocytes from CBA and BALB/c suckers, receiving pyrimidine, activate the RH suppression. Levamizol and prodigiozan exert the same effect on BALB/c mice and inhibit the RH suppression in CBA mice. In mature CBA mice these preparations potentiate HST. The splenocytes from young and aged BALB/c donors receiving the preparations oppositely induce the RH recipients.

[The morphofunctional heterogeneity between peritoneal and alveolar macrophages in their biogenic amine content: the effect of their presence or absence in the microenvironment of mast cells]. / Morfofunktsional'naia geterogennost' mezhdu peritoneal'nymi i al'veoliarnymi makrofagami po soderzhaniiu biogennykh aminov: éffekt prisutstviia ili otsutstviia v mikrookruzhenii tuchnykh kletok.

Peritoneal macrophages differ from alveolar ones in biogenic amine content: peritoneal macrophages contain smaller amounts of histamine and serotonin. When activated, alveolar macrophages release biogenic amines, whereas in peritoneal macrophages stimulators of macrophage activity induce the increase in amine content. This may be due to the presence of mast cells in their microenvironment macrophage activity.

[The mechanism of the combined action of immunomodulators on phagocytic cells]. / K mekhanizmu kombinirovannogo vozdeistviia immunomoduliatorov na fagotsitarnye kletki.

The study revealed that the injection of different immunomodulators (salmosan, levamisole, BCG, prodigiosan) or such irritants as meat-peptone broth led to the formation of heterogeneous macrophage populations, differing in their phagocytic function, oxidation metabolism, secretion of protein products. The additional injection of immunomodulators led neither to further increase in the influx of cells into the abdominal cavity, nor to further activation of the phagocytic function in all cases, irrespective of background and additional preparations used in the experiment. The response was determined by the first stimulus. Each of these macrophage populations was seemingly in a characteristic state of self maintenance during a certain period when it was insensitive to the second stimulus, i.e. the existence of a certain refractory period was revealed. The effect produced by the additional injection was registered only at the expiration of the refractory period. Therefore, the data on the presence of a certain refractory period and its duration for each immunomodulator should be established and taken into consideration in working out the schedule of their combined use.