[The 50th anniversary of the 7th Central Policlinic of Strategic Missile Forces].

The article is devoted to the history of forming and developing of the 7th Central Policlinic of Strategic Missile Forces, which the 22nd of January 2010 has it's 50th anniversary. The article presents the results of activity of the policlinic in promotion of health of servicemen, work, effectuating by policlinic staff in a sphere of reclaiming and involving of modern high-informative methods of diagnostics and treatment, there were given main of them.

Changes in tissue metalloproteinase inhibitor-1 and matrix metalloproteinases during tumor development and metastasizing in mice.

Tissue inhibitor of matrix metalloproteinases type 1, inhibiting the majority of matrix metalloproteinases, can both suppress and stimulate tumor growth. The concentrations and activities of tissue matrix metalloproteinase inhibitor-1 were measured in C57Bl/6 mice during progression and metastasizing of Lewis lung adenocarcinoma. Activities of matrix metalloproteinases in tumor tissue of mice were lower than in liver and lung tissues of intact animals. Serum concentration of tissue inhibitor increased significantly during the development of Lewis lung adenocarcinoma. Macrophage depression (injection of gadolinium chloride associated with a decrease in metastasis number) decreased serum concentration of tissue inhibitor, but it did not attain the control level observed in intact mice. These findings attest to a pleiotropic antitumor effect of tissue matrix metalloproteinase inhibitor-1 reflecting disorders in matrix metalloproteinase regulation during the progress of Lewis lung adenocarcinoma in mice.

[Cystatins: cysteine proteases regulation and disturbances in tumors and inflammation].

Cystatin C belongs to the group of wide spread extracellular cysteine protease inhibitors. Using ELISA kits it was shown that the highest cystatin C concentration was in human cerebrospinal fluid and low cystatin C concentration was in human urine. In healthy young persons serum cystatin C concentration was lower than in elder patients (50-65 year old). In patients with hemoblastoses (lymphoma, lymphogranulomatosis) increased serum cystatin C concentration was normalized after effective antitumor therapy. According to these data one can conclude that serum cystatin C concentration can be used as one of the prognostic criteria in patients with several kinds of hemoblastoses.

Changes in the concentration of tissue inhibitor of type 1 metalloproteinases in blood serum and liver of mice with CCl4-induced hepatitis.

The concentration of tissue inhibitor of type 1 metalloproteinases in blood serum from intact CBA mice measured by enzyme immunoassay is similar to that in healthy humans. The concentration of tissue inhibitor of type 1 metalloproteinases in mouse bile was higher than in blood serum, while its concentration in liver homogenate more than 1000-fold exceeded that in the serum, which attests to its primarily intracellular localization in the liver. Loading of liver cell lysosomes with Triton WR-1339 and development of intrahepatic cholestasis did not affect the concentration of tissue inhibitor of type 1 metalloproteinases in liver homogenate and bile. Administration of CCl4 to mice for 4.5 weeks was accompanied by an increase in the concentration of tissue inhibitor of type 1 metalloproteinases in blood serum, but not in liver homogenate. These changes reflect dysregulation of metalloproteinases, development of inflammation, and progression of the initial stage of connective tissue formation in mouse liver.

[Cystatin C: a biological role and impaired secretion in viral hepatitis c and hepatic cirrhosis].

Cystatin C is a non-glycated cationic protein with a molecular weight of 13.3 kD, which belongs to the superfamily of cystatins; its basic function is to inhibit and regulate the activity of cysteine proteinase. In apparently healthy individuals, the extracellular concentration of cystatin C is shown to be substantially higher in serum than in urine and bile. The increased serum concentration of cystatin C has been found in the development of chronic viral hepatitis C, and hepatic cirrhosis in particular, which reflects the development of an inflammatory process and, evidently, the higher secretion of cystatin C by stimulated macrophages.

Intralysosomal accumulation of gadolinium and lysosomal damage during selective depression of liver macrophages in vivo.

Kinetics of gadolinium accumulation was studied by inductively coupled plasma-emission spectroscopy after intravenous injection of this agent (7.5 mg/kg) to CBA mice. Gadolinium exhibits lysosomotropic properties (long-term selective accumulation in lysosomes in vivo). Gadolinium uptake by hepatic cells attained maximum 1 h after its intravenous injection and remained at this level during the next day. Accumulation of gadolinium in hepatocytic lysosomes disturbed their osmotic properties (as was seen from the increase in free acid phosphatase activity, which persisted for 19 days). Serum activities of beta-D-galactosidase and beta-D-glucuronidase also increased (24-72 h and day 19). Selective depression of liver macrophages (24-48 h) was accompanied by a decrease in serum chitotriosidase activity. We conclude that accumulation of gadolinium in lysosomes of liver macrophages leads to their damage and elimination of a certain population of macrophages (primarily large cells). Changes in activity of serum lysosomal enzymes also reflect repopulation of liver macrophages.

[Effect of stimulation and depression of macrophages on development of paracetamol-induced acute toxic hepatitis in rats]. / Vliianie stimuliatsii i depressii makrofagov na razvitie ostrogo toksicheskogo gepatita u krys, vyzvannogo paratsetamolom.

The role of macrophage (Kupffer cell) stimulation and suppression in the development of a toxic liver damage was studied in rats with acute hepatitis induced by paracetamol (acetaminophen, 1000 mg/kg). Pretreatment with carboxymethylated (1-->3)-beta-D-glucan (25 mg/kg, i.p., 48 h before paracetamol) for the macrophage stimulation or with gadolinium chloride (GdCl3, 7.5 mg/kg, i.v., 24 h before paracetamol) for the macrophage suppression has a protective effect manifested by normalization of the liver function test parameters and by a decrease in the degree of morphological changes in the liver cells. A relation between these positive effects and the TNF-alpha secretion by macrophages is discussed.

Macrophage Stimulator beta-(1-->3)-D-carboxymethylglucan improves the efficiency of chemotherapy of Lewis lung carcinoma.

We studied the effect of macrophage stimulator water-soluble beta-(1-->3)-D-carboxymethylglucan on the efficiency of cyclophosphamide chemotherapy in Lewis lung carcinoma. Cyclophosphamide inhibited the growth of primary tumor nodes by 57%. The preparation possessed pronounced antimetastatic activity: metastases were found in 40.9% animals. Combination therapy with cyclophosphamide and (1-->3)-beta;-D-glucan inhibited the growth of intramuscular tumors by 75-89% and reduced the incidence of metastases into the lungs by 92-94%. The therapeutic effect was most pronounced after simultaneous administration of these preparations: tumor growth was suppressed by 89.3% and metastases were found in only 7.5% animals (vs. 100% in the control). The potentiating effect of beta-(1-->3)-D-carboxymethylglucan is related to accumulation of cysteine proteinase inhibitors in the tumor tissue and plasma, but not to changes in blood cell composition.

[Cooperative effect of hydrocortisone, adrenaline and high-density lipoproteins in regulating the glucose-6-phosphate dehydrogenase activity of the liver]. / O kooperativnom éffekte gidrokortizona, adrenalina i lipoproteidov vysokoi plotnosti v reguliatsii aktivnosti gliukozo-6-fosfatdegidrogenazy v pecheni.

The role of adaptive hormones and serum lipoproteins in the regulation of glucose-6-phosphate dehydrogenase (G-6-PDH) activity was investigated. The test was performed on experimental hepatic sections of Wistar rats. It was shown that timely regulation of G-6-PDH by epinephrine and hydrocortisone which inhibits the activity of enzyme is manifested through the cAMP-dependent mechanism. The cooperative effect of epinephrine, hydrocortisone and high-density lipoproteins that enables G-6-PDH activation was revealed. It was stated that only high-density lipoproteins of subpopulation III were capable of hormonal mediating. The effect was caused by the induction of enzyme synthesis and manifested through lysosome-dependent activation of chromatin.

[Effect of adrenaline, hydrocortisone and serum HDL lipoproteins on the activity of multiple forms of glucose-6-phosphate dehydrogenase in the rat liver]. / Vliianie adrenalina, gidrokortizona i LPVP syvorotki krovi na aktivnost' mnozhestvennykh form gliukozo-6-fosfatdegidrogenazy v pecheni krys.

A decrease in activity of glucose-6-phosphate dehydrogenase (G6PD) in Wistar rat liver tissue, caused by stress, was realized via a mechanism, involving adrenaline and hydrocortisone as first messengers and cAMP as a second messenger. In these systems G6PD II and IV isoenzymes were mainly inhibited. These are the urgent mechanisms for regulation of the enzymatic activity. Activation of G6PD within the reparative period after the stress was due to induction of the enzyme synthesis. Cooperative action of adrenaline, hydrocortisone and high density lipoproteins from blood serum, modulating the effect of adaptive hormones, was responsible for the enzyme induction. Actinomycin D and vinblastine (inhibitor of the cell microtubular apparatus) prevented the stimulation of G6PD isoenzymes caused by the cooperative hormonal effect. The data obtained suggest that the cooperative effect occurred as a result of lysosomes translocation to nucleus and the subsequent activation of chromatin.

[Role of the lysosomes in altering glucose-6-phosphate dehydrogenase activity in the rat liver during intensive physical loading]. / Rol' lizosom v izmenenii aktivnosti gliukozo-6-fosfatdegidrogenazy v pecheni krys pri intensivnoi fizicheskoi nagruzke.

Experiments on rats have shown that heavy exercise induces the synthesis in the liver of the key enzyme of the pentosophosphate pathway, glucose-6-phosphate dehydrogenase. The maximum activity is reached 6 and 16 hours after the exercise. Initiation of the protein synthesis is related to activation of hepatocyte lysosomes and their translocation to the nucleus. Administration to the rats of the blockers of lysosomal translocation or an inhibitor of proteolytic activity one hour before swimming completely removes the inducing effect of lysosomes.

[Analysis of the daily human requirements for thiamine in the newly arrived population of Polar regions]. / Analiz sutochnoi potrebnosti cheloveka v tiamine u prishlogo naseleniia Zapoliar'ia.

The erythrocytes transketolase activity and the TDP-effect were determined in persons residing in the regions beyond the polar circle and these demonstrated a moderate thiamine deficiency. The daily thiamine intake with food in the examined did not exceed 1.5 mg, the thiamine-diphosphate of the epoenzyme amounting to 90 per cent. Following introduction of various pharmacological preparations of vitamin B1 for a space of 2 weeks a somewhat greater transketolase activity and a diminution of the TDP-effect were observed. Administration of cocarboxylase and vitamin B1 with Mg and gelatin more favourable changes were obtained. Some macro- and micro-elements were found to exercise a positive effect on the thiamine assimilation by the tissues. The results obtained indicate that the daily thiamine requirement (allowance) of man in the North does not surpass 1.5-2.0 mg. To control hypovitaminoses in the North it is more effective to use natural vitamin-carriers rather than pharmacological preparations of vitamin B1.