[Effect of lysozyme on the growth of murine lymphoma and antineoplastic activity of cyclophosphamide]. / Vliianie lizotsima na rost myshinoi limfomy i protivoopukholevuiu aktivnost' tsiklofosfamida.

It was shown that hen egg-white lysozyme (LM) in the dose 100 mg/kg under the daily intragastral use slightly inhibited tumor grown or did not influence significantly upon it and did not change antitumor activity of cyclophosphamide. When used at mice C57Bl/6J with the transplanted ascitic or solid T-cell lymphoma EL4 (syngeneic system). On model of the same tumors in ascitic form at mice-hybrids (C57Bl/6J x DBA2)F1 (semisingeneic system) LM significantly potentiates antitumor activity of cyclophosphamide, though it had no effect on the rate of tumor growth. Potentiation of the effect of cyclophosphamide revealed itself in more slow development of ascite, increased mean life-span and the overall survival, appearance of completely cured animals. Our clinic-laboratory studies have revealed a sharp deficit of endogenic lysozyme in the blood serum of leukemic patients and extremely low lysozyme content in lavage liquid, from leukemic patients, with pneumonia. These data suggest that LM can be useful as a food additive in the complex treatment of oncological patients for enhancing antineoplastic chemotherapy efficacy.

[Problems in drug prevention and treatment of endogenous infection and dysbacteriosis]. / Problemy khimioprofilaktiki i khimioterapii endogennoí infektsii i disbakterioz.

Dysbacteriosis is an important pathogenetic condition in the development of endogenous infection whose treatment and prevention are among the most topical and challenging problems. The common cause of dysbacteriosis is antibiotic therapy and prevention of surgical infection. Antibiotic therapy should be performed in accordance to strict indications, with compliance of rational regimens and methods for using drugs. Adequate local and parenteral drugs should be given in wound infection. To prevent endogenous infection, selective gastrointestinal decontamination (SD) that requires bacteriological surveillance of the patient's intestinal microflora and the environment, as well as the use of eubiotics. In critically ill patients with multiple injuries, in patients on artificial pulmonary ventilation, other individuals at risk SD is highly effective, in which oral of intragastric antibiotics which are intestinally unabsorbable and active against only anaerobic opportunistic microbes were added by the same agents for the oral cavity and by lactic acid bifidumbacterin. The new biological drug Bifilys that contains the optimum balanced ratio of bifidobacteria and lysozyme and provides a prompt correction of microbiocenosis, local immunity, and intestinal function is highly effective in the treatment and prevention of dysbacteriosis. Electrochemically activated solutions are also promising in treating dysbacteriosis and digestive infections. There are available original Russian antiviral synthetic and natural agents to make drug therapy and prevention of viral infections frequently complicating the status of weak patients.

[Morphofunctional changes in the lymph nodes and microcirculatory bed of small-intestinal mesentery of dogs in septic peritonitis after endolymphatic administration of ampicillin]. / Morfofunktsional'nye izmeneniia limfaticheskikh uzlov i gemomikro- tsirkuliarnogo rusla bryzheiki tonkoi kishki sobak na fone septicheskogo peritonita pri éndolimfaticheskom vvedenii ampitsillina.

With the aim to study effectiveness+ of endolymphatic (EL) administration of ampicillin (AC), using the model of an acute diffuse septic peritonitis in dogs, the morphological and morphometrical investigation has been performed concerning the state of the lymph nodes (LN), which are regional as regards the pathological focus (pelvic) and remote (tracheobronchial, mesenteric) and hemomicrocirculatory bed (HMCB) of the small intestine mesentery. All LN groups studied are involved in the pathological process, that produces certain increasing disturbances in the structure and cell composition in LN. In 6 h the changes are especially manifested in the pelvic LN, and in 18 h--in the animals without application of AC, or at its intramuscular injection LN lose their typical structure. Their dimensions and number of lymphoid nodules++ and medullary cords decrease, a sharp impoverishment of lymphocytes in LN is observed. By this time critical disturbances in the HMCB structure develop; they are characterized as presence of great amount of avascular areas in the mesentery, extended capillary loops, plasmatic saturation of interstitium. When AC is injected endolymphatically, simultaneously with peritonitis modelling T- and B-dependent zones in LN are preserved, a high volumetric part of lymphocytes is kept in all groups of LN, structure and function of HMCB are normalized. The pronounced delay in development and decreasing manifestation of infective-toxic disorder in LN and HMCB depend on effective concentrations of the antibiotic, produces in the lymphatic system.

[Increasing the effectiveness of ampicillin in combination with lysozyme]. / Povyshenie éffektivnosti ampitsillina pri ego sochetanii s lizotsimom.

The effect of lysozyme (2 mg/kg) on pharmacokinetics of ampicillin (60 mg/kg) and the lymph nodes was studied in a model of experimental diffuse peritonitis in 52 dogs. The drugs were administered intramuscularly in single doses simultaneously with simulation of the pathological process. Under such conditions, lysozyme promoted an increase in the ampicillin concentration in the lymphatic system, blood and tissues and prolonged the antibacterial activity to 18 hours of the experiment. This resulted in retarding lympho- and hematogenic dissemination of the infection from the primary focus and lowered the infectious and toxic affection of the regional lymph nodes, thus securing their barrier and immunological function. With lysozyme used in combination with the antibiotic the immunomorphological zones of the lymph nodes appeared to be preserved and the volumetric proportion of macrophages increased. Then the volumetric proportion of the blast cells and the frequency of macrophagal and lymphocytic interactions also increased. The most pronounced cell interactions were observed in the distal (tracheobronchial) lymph nodes whose functions before the infection generalization were mainly immunological.

[Morphocytochemical reaction of the lymph nodes in dogs to the administration of lysozyme]. / Morfotsitokhimicheskaia reaktsiia limfaticheskikh uzlov sobak na vvedenie lizotsima.

By means of morphological, morphometrical and histochemical methods pelvic and tracheobronchial lymph nodes have been studied in dogs and concentration of lysozyme has been estimated in blood serum, in lymph and the lymph nodes after a single intramuscular injection of lysozyme (2 mg/kg of body mass). In the material investigated total concentration of lysozyme reaches its maximal values in 6 h after injection, then it gradually decreases and in 48 h reaches its control level. Morphometrically changes in cell composition are revealed predominantly of immune-competent cells in T- and B-dependent zones of the lymph nodes. Thus, the volumetric part of lymphoblasts in the germinative centers of the lymphoid nodules reaches its maximal indices by 48 h after lysozyme injection, while plasmatization of the paracortical zone and of medullary cords increases up to the 7th day. By the 14th day the volumetric part of lymphoblasts, immunoblasts and plasmocytes decreases gradually, and in 21 days after injection of the drug contents of the blast forms of the cells in the structural-functional zones of the lymph nodes does not differ from that in the control. The data obtained demonstrate the immunomorphological rearrangement of the lymph nodes in response to the exogenic lysozyme administration.

[Quantitative spectrophotometric determination of prodigiozan in the visible spectrum]. / Kolichestvennoe spektrofotometricheskoe opredelenie prodigiozana v vidimoi oblasti spektra.

A procedure for quantitative determination of prodigiosan in 0.02 per cent solutions in the visible region of the spectrum is described. The procedure is based on the ability of prodigiosan to affect the spectral properties of 1-ethyl-2-[3-(ethylnaphthyl [1,2d]-thiazolin-3-imidine)-2methyl propenyl]-naphtho-[1,2d]-thiazolin bromide (a dye).

[Metabolism and function of phagocytes after combined administration of immunosuppressants and biologically active substances]. / Metabolizm i funktsii fagotsitov pri sochetannom primenenii immunodepressorov i biologicheski aktivnykh veshchestv.

Metabolism and function of mouse phagocytes were studied experimentally under conditions of immunosuppression with biologically active substances. It was shown by the cytochemical methods with the use of cytophotometry that strong immunosuppression with azathioprin, prednisolone, especially with their combination induced inhibition of the enzymatic systems responsible for synthetic and energy processes in macrophages. Prodigiosan, a bacterial lipopolysaccharide, and lysozyme promoted elimination of the unfavourable effect of the immunosuppressors on macrophage metabolism, normalizing the decreased activity of certain enzymes and markedly activating the enzymes involved in detoxification and phagocytosis. The lysozyme effect did not depend on the type of drug immunosuppression. The efficiency of prodigiosan was the highest after administration of prednisolone or its combination with azathioprin. Its effect was lower after immunosuppression with azathioprin alone. During allotransplantation, prodigiosan also promoted the recovery of the leukocyte adsorption and digestive capacity impaired by prednisolone and tis combination with azathioprin. The differential use of the biologically active substances is a promising trend in control of complications due to immunosuppression therapy.

[Effect of prodigiozan and lysozyme on the surface structures of macrophages after immunosuppression]. / Vliianie prodigiozana i lizotsima na poverkhnostnye struktury makrofagov v usloviiakh immunodepressii.

The state of macrophage surface structures is closely connected with the function 1 capacity of these cells. Peritoneal macrophages from mice subjected to strong 10-day immunosuppression with azathioprine (60 mg/kg), prednisolone (50 mg/kg) or their combination (25 and 30 mg/kg, respectively) were investigated with scanning electron microscopy. Azathioprine and especially its combination with prednisolone induced pronounced degenerative affections in the macrophages and lymphocytes, smoothing of their surfaces, predominance of large spread macrophages, and impairment of the intracellular cooperation. The macrophage alteration under the action of prednisolone was less pronounced. Prodigiozan, a bacterial polysaccharide (0.5 mg/kg) administered on the 4th and 9th days of the immunosuppression increased the macrophage resistance mainly to the damaging effect of prednisolone and was low effective after administration of azathioprine. The effect of lysozyme injected intramuscularly in a dose of 0.5 mg/kg daily within a period of the 3rd to the 10th days of the use of the immunosuppressants was evident from activation of the surface structures of the small macrophages and lymphocytes and reduction of cell alterations independent of the type of the immunosuppressants used. This indicates the necessity of a differential approach to the use of the macrophage activators for correcting the decreased infection resistance after medicamentous immunosuppression.

[Spectrophotometric determination of prodigiozan in ampule solutions]. / Spektrofotometricheskoe opredelenie prodigiozana v ampul'nykh rastvorakh.

Based on a study of the absorption properties of prodigiosan it has been shown that its UV absorption spectrum is characterized by an arm at 250-260 nm with an inflection point at 260 nm. The concentration ranges within which the optical density of prodigiosan solution obeyed the Bouguer-Lambert-Beer law were measured. This allowed the development of a quantitative spectrophotometric method for determination of prodigiosan in ampouled solutions.

[Experimental effect of lysozyme on macrophage metabolism and resistance to infection]. / Vliianie lizotsina na metabolizm makrofagov i protivoinfektsionnuiu rezistentnost' v éksperimente.

The peritoneal macrophages of mice treated with lysozyme were studied by cytochemical assay. In single and repeated doses of 0.5-5 mg/kg lysozyme induced an increase in macrophage metabolism. This was evident from an increased activity of succinate dehydrogenase, NADP X N-DH and the enzymes catalyzing glycolysis typical of these cells (lactate dehydrogenase and alpha-glycerophosphate). The changes in the activity of the enzymatic systems were most pronounced in minute and less mature macrophages after repeated administrations of the drugs. In a dose of 50 mg/kg lysozyme somewhat decreased the activity of a number of the enzymes. In the doses optimal for the macrophage activity lysozyme had a low effect on the infection resistance and slightly increased the cephotaxim efficiency in experimental staphylococcal infection. This may be mainly due to the immunomodulating effect of lysozyme and its low effect on the large macrophages having the bactericidal effect.

[Effect of lysozyme on the surface structures of mouse peritoneal macrophages]. / Vliianie lizotsima na poverkhnostnye struktury peritoneal'nykh makrofagov myshei.

Surface structures of the peritoneal macrophages of BALB/c mice treated intramuscularly with various doses of egg lysozyme (0.05 to 50 mg/kg) were studied with scanning electron microscopy. It was shown that the effect of lysozyme on the macrophages significantly depended on the dose of the preparation and the frequency of its use. When used in the subtherapeutic (0.5 mg/kg) and therapeutic (5 mg/kg) single doses, lysozyme promoted detection of heterogeneity of the macrophage population, marked activation of their surface membranes and intensification of intercellular cooperation. The highest level of the lysozyme activating effect on the minor macrophages and lymphocytes was observed after administration of the preparation in a single dose of 5 mg/kg or in a dose of 0.5 mg/kg repeatedly (daily for 7 days). When used in a dose of 5 mg/kg repeatedly or especially in a single dose of 50 mg/kg lysozyme induced smoothing of the surface of the macrophages and lymphocytes. The problems of indirect, direct and immune activation of the macrophages with lysozyme are discussed.

[Experimental study of the endolymphatic use of gentamycin and klaforan (cefotaxime)]. / Eksperimental'noe izuchenie éndolimfaticheskogo primeneniia gentamitsina i klaforana (tsefotaksima).

Distribution of gentamycin and klaforan in the lymphatic system, blood and cerebrospinal fluid, as well as their effect on lymph node morphology was studied experimentally on 46 dogs. The antibiotics were administered endolymphatically in doses of 1 and 30 mg/kg respectively. The highest levels of gentamycin (200-250 micrograms/ml) and klaforan (up to 1600 micrograms/ml) were detected in the central lymph. The therapeutic levels of the antibiotics in the central persisted for 24 and 72 hours respectively. The antibiotics accumulated mainly in the regional (inguinal and pelvic) lymph nodes, where their high levels were determined for 72 hours. The levels of the antibiotics in the distant (cervical and tracheobronchial) lymph nodes were lower and did not exceed the therapeutic ones. They persisted for 6 and 24 hours respectively. No unfavourable effect of the antibiotics on the structure and cell composition of the lymph nodes was noted. After endolymphatic administration in the above doses the antibiotic levels in the blood serum were close to those observed after administration by the routine routes. After endolymphatic administration in the above doses the antibiotics penetrated into the cerebrospinal fluid.

[Prodigiozan as an activator of peritoneal macrophages]. / Prodigiozan kak aktivator peritoneal'nykh makrofagov.

The quantitative cytochemical investigation of the prodigiozan effect on the enzymatic activity of the peritoneal macrophages was performed on mice. The drug was administered in a single dose of 150 microgram/kg 24 hours before the specimen collection. Prodigiozan promoted a reliable increase in the activity of the enzymes participating in glycolysis (lactate and cytoplasmic alpha-glycerophosphate dehydrogenases), hexoso-monophosphatic pathway of glucose oxidation (glucoso-6-phosphate dehydrogenase), succinate dehydrogenase, NADP. N-diaphorase and lysosomal enzymes, such as acid phosphatase and non-specific alpha-naphthyl acetate esterase. The changes indicate that activation of the macrophages is one of the significant mechanisms of increasing the host nonspecific resistance with prodigiozan.

[Histochemical study of sodium nucleinate-activated peritoneal macrophages]. / Gistokhimicheskoe izuchenie peritoneal'nykh makrofagov, aktivirovannykh nukleinatom natriia.

The activity of various enzyme groups and the levels of protein and glycogen in the peritoneal macrophages of CBA mice treated intraperitoneally with sodium nucleinate were determined histochemically with the use of cytophotometry. A significant increase in the activity of the lysosomal enzymes, such as acid phosphatase and nonspecific esterases and an increase in the activity of lactate, malate, glutamate, alpha-glycerophosphate, and beta-hydroxybutyrate dehydrogenases. NAD.H- and NADF.H-diaphorases accompanied by an increase in the level of the total protein and glycogen were observed. Analysis of the changes was indicative of an increase in the inherent physiological metabolic and functional level under the effect of sodium nucleinate. It is suggested that the macrophage sub-populations with an increased metabolic activity appeared in the peritoneal exudate of the stimulated animals. Participation of the host low molecular DNA in the maintenance of the physiological level of th nonspecific antiinfectious resistance is suggested.

[Effect of prodigiozan on the surface structures of peritoneal macrophages under the scanning electron microscope]. / Izuchenie vliianiia prodigiozana na poverkhnostnye structury peritoneal'nykh makrofagov v skaniruiushchem élektronnom mikroskope.

The surface structures of peritoneal macrophages of mice were investigated with a scanning electron microscope RZEM-500. The study revealed 3 types of the macrophages. Macrophages of type 1 predominated in intact mice. These macrophages are cells rounded or oval in shape with a great number of compact finger-like excresences differing in size and form. In the animals treated with prodigiozan in a single dose of 150 mg/kg, the majority of the macrophages were larger in size and had a changed surface: spread, with many branches, "train", undulated membranes. Formation of a great number of macrophagal and macrophagal-lymphocytic clusters evident of the increased cell cooperation under the effect of prodigiozan was shown. The morphological changes in the surface structures of the macrophages under the effect of prodigiozan in vivo indicate an increase in their functional activity.

[Stimulation of nonspecific body resistance in transplantation]. / Stimuliatsiia nespetsificheskoi rezistentnosti organizma pri transplantatsii.

The experiments on mice showed in principle a possibility of using prodigiozan, a stimulant of the host immunobiological reactivity together with immunodepressants in transplantation. Imuran in doses of 25 or 60 mg/kg and prednisolone in doses of 30 or 50 mg/kg were used on alternate days at a rate of 5 injections of every drug per course. Prodigiozan was administered intramuscularly in a dose of 0.5 mg/kg on the 4th and 8th-9th days of the immunodepressant administration. Addition of prodigiozan to the scheme of the combined use of the immunodepressants provided an increase in the survival rate of mice with staphylococcal and coli infections and prolongation of the skin allotransplant rejection time. No effect of prodigiozan on immune depression due to imuran was observed. The results suggest that screening of drugs for the use in transplanthology for prevention of infectious complications in the presence of immunostimulants is advisable among stimulants of the host nonspecific resistance.

[Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body]. / Vliianie gentamitsina v sochetanii s prodigiozanom na immunologicheskuiu reaktivnost' organizma.

The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.

[Effect of gentamicin on the state of cellular resistance]. / Vliianie gentamitsina na sostoianie kletochnoi rezistentnosti

The effect of gentamicin on the functional state of the cells of the reticuloendothelial system (RES) of the abdominal cavity of mouse macrophages and the cell culture of the rabbit embryon kidneys was studied. Gentamicin administered intramuscularly in multiple doses of I and 10 mg/kg for 6--14 days did not induce significant changes in the absorptive activity of the RES. In doses of 20 and 40 mg/kg gentamicin induced some inhibition of the absorptive activity of the abdominal cavity macrophages, which was accompanied by a decrease in the content of the total protein and an increase in the activity of the acid phosphatase in the cell cytoplasm. The changes were reversible and persisted for not more than 48 hours after the last administration of the antibiotic. Gentamicin inhibited the cell growth in the culture of the rabbit embryon kidneys in concentrations higher than 1000 mg/kg, LD50 of gentamicin for mice weighing 20--22 gm being 244 mg/kg. Preliminary administration of amigluracyl provided a decrease in the toxic effect of gentamicin in both the cell culture and the host, which was possibly associated with the anabolyzing effect of amigluracyl.