[Safety research of a vaccine preparation in hepatitis A derived from the MB-7 rapidly growing strain]. / Izuchenie bezvrednosti vaktsinnogo preparata protiv gepatita A iz bystrorastushchego shtamma MB-7.

A study was undertaken to prove that a vaccine drug based on the fast-growing MB-7 (MB-7 VD) of hepatitis A virus (HAV) is safe. It was established that MB-7 VD, when once injected to white outbred mice and when 4 times injected to Hartley guineas pigs, did not cause any hematological and biochemical changes in the peripheral blood or in the condition of the central nervous system of experimental animals, which shows that MB-7 VD is free of any toxic properties.

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

Liver resistance to toxic effects of CCl(4) under conditions of gadolinium chloride depression of Kupffer cells.

Acute toxic hepatitis was modeled in (CBAxC57B1)F1 mice by single injection of 40% CCl(4) in oil. Pretreatment with gadolinium chloride, a selective blocker of Kupffer cells, considerably potentiated damage to hepatocytes leading to generalization of this process, delayed inflammatory infiltration, and inhibited reparative processes. Zymosan administered against the background of gadolinium chloride blockade improved liver resistance to CCl(4)-induced damage, intensified mononuclear infiltration, and accelerated reparative processes.

Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis.

In rats with CCl4-induced liver cirrhosis, a twofold decrease of blood clearance rate and a fourfold reduction in number of Kupffer cells taking up colloidal carbon particles has been demonstrated. Zymosan stimulation does not lead to granuloma-like structures in the liver of CCl4-cirrhotic rats. In cirrhotic rats, unlike controls, the cathepsin D activity of liver tissue is very little increased by zymosan treatment and there is virtually no increase in collagenolytic activity. The increase in PGE content in cirrhotic rat liver after prodigiosan stimulation was 2.5 times less than in stimulated control animals. In cirrhotic rats, the IL-1 producing capacity of blood monocytes in vitro in response to lipopolysaccharide drops almost fivefold. The total count of bone marrow-derived myeloid colonies in cirrhotic zymosan-stimulated animals was reduced by 1.5-fold whereas in control animals zymosan induced a 1.8-fold increase in the number of myeloid colonies. The number, uptake and nitroblue tetrazolium-reducing capacities of lung, spleen, peritoneal and bone marrow macrophages in animals with liver cirrhosis were only slightly increased in response to zymosan as compared to control animals. The low response of extrahepatic macrophages to stimuli in cirrhotic animals is thought to be due to their premobilization during the development of cirrhosis.

[Functional state of the hematopoietic system in different stages of CCL4-induced liver fibrosis in mice]. / Funktsional'noe sostoianie sistemy gemopoéza na raznykh stadiiakh CCL4-gepatofibroza u myshei.

The state of hemopoietic system at different stages of CCL4-induced liver fibrosis in mice and its reaction to stimuli was examined. At early stages of liver fibrosis (2 weeks of CCL4-administration) we observed a disinhibition of granulo-monocytopoiesis. This is manifested in an increase of the number of immature granulocytes, monocytes/macrophages and CFU-GM in the bone marrow. After 24 h of zymosan injection in this stage an increase of both bone marrow CFU-GM and CFU-E, and the rate of serum colony stimulating activity (CSA) occurred. On the contrary, in advanced liver fibrosis (16 weeks of CCL4 administration), the rate of both granulo-monocytopoiesis and erythropoiesis were decreased as compared with the preceding stage of the process and the response to zymosan became perverted: the number of CFU-GM was paradoxically decreased, while the number of CFU-E remained practically unchanged. The rate of serum CSA increased very poorly too. Thus, in advanced liver fibrosis the hemopoietic system is functionally defective and this factor may be important in development of fibrotic process in the liver.

[Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis]. / Funktsional'nye perestroiki sistemy mononuklearnykh fagotsitov pri éksperimental'nom tsirroze pecheni.

In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis.

[Effect of lysozyme on hepatocyte resistance]. / Vliianie lizotsima na rezistentnost' gepatotsitov.

Antitoxic effect of lysozyme was shown on a model of experimental acute toxic hepatitis of rats and mice. Administration of lysozyme to the animals in a dose of 5 mg/kg 24 hours before administration of carbon tetrachloride markedly decreased the level of morphological damages in the liver tissue and promoted a decrease in increased levels of alanine aminotransferase in blood serum. Higher levels of lysozyme in blood serum and cells of mouse peritoneal exudate 3 hours after administration of lysozyme were observed. The role of lysozyme as one of the main products secreted by activated macrophages in providing the general and antitoxic resistance of hepatocytes is discussed. Possible use of lysozyme as a hepatoprotective agent is suggested.

Role of the functional state of the liver RES in the pathogenesis of toxic liver injury.

In rats to which E. coli endotoxin (250 micrograms/kg i.p.) was administered 24 h before they were given tetrachlormethane (CCl4) (1.5 ml/kg intragastrically), stimulation of liver DNA synthesis was observed during the first 48 h after administration of the hepatatoxin. In experimental rats to which prodigiosan (a Serratia marcescens polysaccharide, 250 micrograms/kg i.p.) was administered 24 h before CCl4 (1.5 ml/kg i.p.), liver damage 24 h after CCl4 poisoning was expressed less--judging from the size of liver necrosis and the size of glycogen-free zones in the liver lobules than in the controls. To elucidate the role of activated macrophages in the induction of liver resistance to CCl4, liver injury caused by this hepatotoxin was compared after the pre-administration of protein extract from the Kupffer cells or hepatocytes of prodigiosan-stimulated rats. In rats given the larger dose of Kupffer cell extract (6 mg/ml i.p.), the necrotic foci formed after the administration of CCl4 were significantly smaller. The results confirm the conception that liver macrophages participate in the development of resistance to CCl4.

[Development of liver cirrhosis in rats following stimulation of hepatic macrophages]. / Osobennosti razvitiia tsirroza pecheni u krys pri stimuliatsii pechenochnykh makrofagov.

Liver cirrhosis was induced in male Wistar rats weighing 200-250 g by subcutaneous injection of 0.25 ml of a 10% CCl4 solution per 100 g bw. Kupffer cells were stimulated with prodigiozan which was introduced at a 10-day interval in the course of fibrosis development. Under stimulation the injury to the parenchyma decreased; the total number of Kupffer macrophages and the degree of mononuclear infiltration of liver tissue increased, while fibroplasia diminished. The content of hydroxyproline in liver homogenates of prodigiozan-stimulated rats was half as much as compared with controls.

[Effect of Kupffer cell blockade on the development of acute toxic hepatitis]. / Vliianie blokady kletok Kupfera na razvitie ostrogo toksicheskogo gepatita.

The blockade of Kupffer cells was induced in Wistar rats by intravenous injection of colloid iron, brand P-100 phi, in a 5% starch followed after two hours by subcutaneous administration of 0.2 ml of 40% CCl per 100 g body weight. During the blockade of course of CCl4-induced acute hepatitis was significantly modified that was shown by the tendency to scattering of hepatocyte injury and by delayed liver tissue recovery.

[Function activity of blood polynuclears according to results of the nitroblue tetrazolium reaction in inhabitants of the Far North]. / Funktsional'naia aktivnost' polinkulearov krovi po dannym reaktsii s nitrosinim tetrazoliem u zhitelei Krainego Severa.

The functional activity of polynuclear cells was studied in clinically healthy males aged 20-45 years constantly living in medium latitudes (the control group) and high latitudes (the experimental group). In persons who had lived in the North for a period of 6 months to 10 years and more the results of the spontaneous test with the use of nitrotetrazolium blue differed slightly from those in the control group, whereas after the stimulation of blood neutrophils with bacterial endotoxin these results proved to be significantly lower than those in the control group. With the increase of the time of residence in the North a tendency to greater individual differences in the results of the test with the use of nitrotetrazolium blue appeared, very low results being observed alongside very high ones. These facts indicate that under the extreme conditions prevailing in the arctic areas the reactivity of human neutrophils to bacterial stimulators is inhibited.

[Characteristics of the development of acute toxic hepatitis in rats stimulated with prodigiozan]. / Osobennosti razvitiia ostrogo toksicheskogo gepatita u krys, stimulirovannykh prodigiozanom.

Acute toxic hepatitis was induced in Wistar rats by means of a single injection of 40% CCl4 on a peach-kernell oil base (0.2 ml/100 g body weight). Under conditions of stimulation with the bacterial polysaccharide prodigiosan, the resistance of hepatocytes to CCl4 sharply increased, which was shown by diminished severity of hepatic parenchyma destruction.