[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.

[Use of prodigiozan and tactivin for treatment of patients with chronic Klebsiella infections]. / Ispol'zovanie prodigiozana i taktivina v lechenii bol'nykh khronicheskimi klebsiellezami.

Two-stage immunocorrection in patients with chronic Klebsiella infections by consecutive administration of prodigiozan and tactivin, has been shown to facilitate the restoration of the balance of immunoregulating cells, to enhance proliferative response to T- and B-mitogens, thus producing favorable clinical dynamics. The possibility of chronic Klebsiella infections therapy, based on the use of immunocorrecting preparations (prodigiozan and tactivin) and antibiotics capable of intracellular penetration (sumamed and cyprofloxacin) is discussed.

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

[Hemorheological indices in patients with amebic abscesses of the liver and their correction]. / Gemoreologicheskie pokazateli u bol'nykh s amebnymi abstsessami pecheni i ikh korrektsiia.

Hemorheological indices were studied in 89 patients. In 61 patients the authors have revealed somewhat increased viscosity potential of blood and negligible changes in the aggregation activity of erythrocytes which is thought by the authors to be due to the saved compensatory potentialities of the organism. In 28 patients with the complicated course of the disease the rheological parameters of blood became worse because of the suppressed compensatory potentialities of organism. So, in addition to the adequate transfusion-infusion therapy the complex of treatment must include immunostimulating means (Levamisole, Prodigiozan, Tactivin etc.).

[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.

[Role of neutrophilic leukocytes in pathogenesis of idiopathic fibrosing pulmonary alveolitis]. / Rol' neitrofil'nykh leikotsitov v patogeneze idiopaticheskogo fibroznogo al'veolita.

The study was undertaken to obtain additional data on the role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Various functional parameters of neutrophilic functional activity, i.e. phagocytosis, chemotaxis, random migration, oxidative metabolism (3 types of chemiluminescence: spontaneous formylmethionyl peptide-stimulated, and prodigiosan-stimulated), and the level of circulating immune complexes of different size were determined in patients with IPF and healthy individuals. The patients showed a decrease in phagocytosis and an increase in neutrophilic chemotaxis and oxidative metabolism, which was related to the output of toxic oxygen forms. The changes revealed were found to be associated with the activity of an pathological process. The findings suggest that neutrophils can be involved both in the development of and in the occurrence of a pathological process in IPF.

[The production of inflammation mediators by mouse peritoneal cells under conditions of combined exposure to staphylococcal enterotoxin and lipopolysaccharide]. / Produktsiia mediatorov vospaleniia peritoneal'nymi kletkami myshei v usloviiakh sochetannogo vozdeistviia stafilokokkovogo énterotoksina i lipopolisakharida.

The influence of staphylococcal enterotoxin of type A (SEA) and enterobacterial lipopolysaccharide (LPS) on the production of tumor necrosis factor alpha (TNF alpha), gamma-interferon and active forms of oxygen by mouse peritoneal cells was studied. Both SEA and LPS, when injected to animals, produced stimulating influence on the oxygen metabolism of phagocytizing cells. The highest toxic doses of LPS induced the maximal generation of oxygen radicals. Under the conditions of the development of lethal toxic shock, i.e. after the combined injection of SEA and LPS, the synergic activation of oxygen metabolism was observed, which was also manifested by the pronounced production of TNF alpha and the increased synthesis of gamma-interferon.

[The use of prodigiozan in the combined therapy of the sequelae of mild craniocerebral trauma]. / Primenenie prodigiozana v kompleksnoi terapii posledstvii legkoi cherepno-mozgovoi travmy.

Based on findings secured with the aid of instrumental and immunological techniques (electroencephalography, echoencephalography, roentgenoencephalography) a total of 57 patients with sequelae of mild craniocerebral injury were examined. Used in the study as an immunomodulating agent was prodigiosan. The drug was found to improve the bioelectrical activity of the brain, and to increase the amplitude of blood filling as evidenced by neurophysiological investigations. Moreover, prodigiosan makes for reduction of vegetovascular disorders and epileptic seizures, returning the level of neurospecific proteins to normal.