Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.

COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA -0.10 ± 0.13ΔlogCFU versus -0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference -0.01, 95% CI -0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.

Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis.

RATIONALE: Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients. METHODS: Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv. RESULTS: All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy's criteria for serious liver injury. CONCLUSIONS: The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01225640.

Human mesenchymal stromal cells can uptake and release ciprofloxacin, acquiring in vitro anti-bacterial activity.

BACKGROUND AIMS: Traditional antibiotic therapy is based on the oral or systemic injection of antibiotics that are often unable to stop a deep infection (eg, osteomyelitis). We studied whether or not bone marrow stromal cells (BM-MSCs) are able to uptake and release ciprofloxacin (CPX), a fluoroquinolone considered the drug of choice for the treatment of chronic osteomyelitis because of its favorable penetration into poorly vascularized sites of infection. METHODS: Human bone marrow stromal cells (BM-MSCs) were primed with CPX (BM-MSCsCPX) according to a methodology previously standardized in our laboratory for paclitaxel (PTX). The anti-microbial activity of CPX released from BM-MSCs cells (BM-MSCsCPX-CM) or supernatant from cell lysate (BM-MSCsCPX-LYS) was evaluated by agar dilution and microdilution methods on three bacterial strains (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). To investigate whether or not primed cells (BM-MSCsCPX) were able to directly act on the bacterial growth, co-colture was performed by mixing E. coli suspension to an increasing number of BM-MSCsCPX. The anti-bacterial activity was determined as number of BM-MSCsCPX that completely inhibited bacterial growth. RESULTS: The results demonstrated that BM-MSCsCPX are able to uptake and then release CPX in the conditioned medium. The loaded antibiotic maintains its active form throughout the process as tested on bacteria. CONCLUSIONS: Our findings suggest that CPX-loaded MSCs may represent an important device for carrying and delivering CPX (and perhaps other antibiotics) into infected deep microenvironments; they could be used for local application and by systemic infusion when their homing capacity into the bone is cleared.

Effects of dietary bovine lactoferrin on growth, physiological performance, iron metabolism and non-specific immune responses of Siberian sturgeon Acipenser baeri.

The present experiment was carried out to investigate the effects of different levels of dietary lactoferrin (LF) on growth performance, physiological status, iron absorption and innate immune response of juvenile Siberian sturgeon Acipenser baeri. Fish were fed with six different rations including 0, 100, 200, 400, 800 and 1600 mg LF kg(-1) diet for 8 weeks. At the end of the experiment, samples were collected for estimating the physiological and immunological parameters. Dietary LF did not change the fish growth performance, hematological parameters, serum proteins or hepatic enzymes. Moreover, stress indicators (plasma cortisol, glucose and lactate) were not affected by dietary LF. The iron absorption of fish was considerably affected by LF; thus, plasma iron in LF-treatments greatly declined and the total iron binding capacity (TIBC) significantly increased in fish fed with 800 mg LF kg(-1). In addition, the liver iron content markedly increased in some LF-treatments, but the variation of muscle iron concentration in treatments was insignificant. The amount of mucus secretion and serum bactericidal activity rose in fish fed on dietary LF, although other non-specific immune responses such as mucus bactericidal activity, serum and mucus lysozyme activity, serum peroxidase, serum natural hemolytic complement activity and serum IgM were not influenced by LF. This study revealed the ability of dietary LF to sequester iron, which is an essential nutrient required for the growth of bacteria. LF was also shown to improve some physiological and immunological parameters of Siberian sturgeon, to some extent.

Protective effect of hainosankyuto, a traditional Japanese medicine, on Streptococcus pyogenes infection in murine model.

BACKGROUND: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto-treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage. CONCLUSIONS/SIGNIFICANCE: Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically.

Effects of dietary vitamin C on neutrophil function and responses to intramammary infusion of lipopolysaccharide in periparturient dairy cows.

Neutrophil function and the severity and incidence of mastitis in dairy cows is related to the intake of many antioxidant nutrients. Because vitamin C is the major water-soluble antioxidant in mammals, we examined the effect of dietary vitamin C on neutrophil function and responses to intramammary infusion of lipopolysaccahride (LPS) in periparturient dairy cows. At 2 wk before anticipated calving, Holstein cows were fed diets that provided 0 (16 cows) or 30 (15 cows) g/d of supplemental vitamin C (phosphorylated ascorbic acid). Treatments continued until 7 d after cows received an infusion of 10 microg of LPS into one quarter of the mammary gland (on average, this occurred 32 d postcalving). Supplementation of vitamin C increased plasma concentrations of vitamin C at calving, but no differences were observed in samples taken 24 h postinfusion. Concentrations of vitamin C in milk (24 h postinfusion) and in neutrophils (calving and 24 h postinfusion) were not affected by treatment, but vitamin C concentrations in neutrophils isolated from milk were about 3 times greater than concentrations in blood neutrophils. The LPS infusion did not alter concentrations of vitamin C in plasma or milk, suggesting that the LPS model did not produce the same effects as a bacterial infection of the mammary gland with respect to antioxidant effects. Supplemental vitamin C had no effect on neutrophil phagocytosis or bacterial kill. Dietary vitamin C reduced the milk somatic cell count but did not affect the febrile response or milk production following LPS infusion.

[Use of zeolite-containing biologically active food supplement in patients with burn trauma]. / Primenenie tseolitsoderzhashchei biologicheski aktivnoi dobavki k pishche u patsientov s ozhogovoi travmoi.

The content of cationic protein in blood neutrophils, the serum activity of lysosomal enzymes, the intensity of peroxide lipid oxidation, the antioxidant serum activity and the blood concentration of trace elements were assessed in patients with burn injury. Some patients as addition to the main therapy got zeolyt-containing biological active addition to food (BAAF) "Lytovit" with its ability for sorption and selective ion exchange. Before the beginning of the treatment in all patients high value of the cationic protein degranulation, decrease of neutrophils biocidity, and increase of lipid peroxidation against a background of antioxidant activity were found. In patients, who had got zeolyt containing BAAF, the normalization of trace elements blood concentration and indices of neutrophils functional activity began earlier, then in patients without zeolyt containing biological active addition treatment. "Lytovit" promoted the more early regress of the clinic manifestations: the body temperature normalization, wounds self-cleaning from purulent discharge, diminishing of frequency and area of the grafts lysis.

Effect of vitamin C on neutrophil function after high-intensity exercise.

High-intensity exercise leads to an increased risk of upper respiratory tract infections in athletes, which had been related to an exercise-induced impairment of neutrophil function. In this study, several indices of neutrophil function were analysed before and after a biathlon and the effect of oral vitamin C on neutrophil function was determined. Six athletes took 2 g vitamin C daily for 1 week prior to a biathlon and four athletes did not take any supplementation. Neutrophil phagocytosis was analysed by fluorescence microscopy and flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Reactive oxygen production was analysed by flow cytometry. Catecholamines were analysed by high-performance liquid chromatography. After high-intensity exercise there were significant reductions in the number of phagocytosed Escherichia coli per neutrophil and in neutrophil bactericidal ability. There was a significant exercise-dependent increase of catecholamines. There was no difference between the two groups of athletes. These results do not support the concept that vitamin C supplementation corrects neutrophil dysfunction after strenuous exercise.

Effects of beta-carotene, selenium and vitamin A on in vitro polymorphonuclear leukocytic activity in peripartal buffalo (Bubalus bubalus).

The effect of different concentrations of three antioxidans on phagocytic and kill activities of blood polymorphonuclear leukocytes (PMN) isolated from buffaloes during the peripartum period (4 weeks before to 7 weeks after parturition) was investigated in this study. Two concentrations of beta-carotene and vitamin A (10(-6) and 10(-5) M) and one concentration of Se (10(-9) M) were used. Phagocytic activity of PMN treated with beta-carotene (10(-6)M) significantly enhanced (P < 0.05) after parturition (Week 0 until Week 3), whereas the kill activity of the same cells significantly (P < 0.05) increased before and after parturition (at Weeks -4, -3, -2, 0, 1, 2 and 3). The concentration of beta-carotene (10(-5) M) enhanced phagocytosis of PMN only at Weeks 0 and 1 and kill activity at Weeks -4, -3, -2, 0, and 1. Selenium (10(-9)M) significantly (P < 0.05) enhanced phagocytic activity of PMN starting from parturition (Week 0) until Week 3 postpartum. Kill activity increased significantly both before (Weeks -4, -3 and -2) and after (Weeks 0, 1, 2, 3 and 4) parturition. Vitamin A (10(-6) M) significantly enhanced phagocytic activity of PMN at Weeks 0, 1, and 2, whereas, the concentration of beta-carotene (10(-5) M) increased phagocytic activity only at Week 0. Kill activity of PMN increased significantly (P < 0.05) at Weeks -1 and 0 (10(-6)M). These results demonstrate that beta-carotene and selenium significantly enhanced phagocytic and kill activities of PMN isolated from buffaloes around parturition in vitro. Vitamin A enhanced phagocytosis and kill activities but not to the same extent as beta-carotene and selenium. Apparently, the in vitro killing activity of PMN is a distinctive function from phagocytosis and both activities may be enhanced by the use of essential nutrients, especially during the peripartum period. Moreover, beta-carotene is more effective as an antioxidant than vitamin A in enhancing the activities of phagocytic cells.

Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice.

Maitake D-fraction, beta1,6-glucan having beta1,3-branches, has been reported to activate the immune system of the host. To elucidate whether the D-fraction can reduce the clinical effective dosage of antibiotics in the treatment of opportunistic bacterial infection, we examined the effects of D-fraction on the treatment of Listeria monocytogenes-infected mice in combination with vancomycine (VCM), the only antibiotic used for methicillin-resistant Staphylococcus aureus (MRSA). Listeria-infection was introduced by its inoculation into the abdominal cavity of mice. Without treatment, all inoculated mice died within 3 days after the inoculation. In contrast, in the mice treated with combined therapy of D-faction (10 mg/kg per day) and VCM (10 mg/kg per day), the survival rate was maintained at 60% on the 10th day after the inoculation, which was superior to that of mice treated with VCM alone (10 mg/kg per day). To investigate the mechanism underlying the reinforcement of VCM treatment by the D-fraction, the activities of macrophages and splenic T cells of Listeria-infected mice were evaluated. In mice administered with both D-fraction and VCM, macrophages produced 2.7 times as much interleukin-1 as that of non-treated control mice. The bactericidal activity of splenic T cells was also enhanced by 2.6 times of that of non-treated control mice. These results indicate that D-fraction activates immuno-competent cells, induced cytokine production, and consequently enhanced the bactericidal activities of the splenic T cells against Listeria monocytogenes, suggesting the clinical benefit of D-fraction in the case of anti-bacterial treatment for patients with high risks.

Effects of areca nut extracts on the functions of human neutrophils in vitro.

Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils. Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner. At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye. However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction. Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE. Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used. Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs. In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils. This effect may contribute to a less efficient elimination of bacteria from the periodontal environment. Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products.

Vitamin concentration and function of leukocytes from dairy calves supplemented with vitamin A, vitamin E, and beta-carotene in vitro.

Blood neutrophils and pulmonary alveolar macrophages, isolated from calves at 3 and 6 wk of age, were cultured in medium without added vitamins or supplemented with 100 micrograms/dl of vitamin A, 1000 micrograms/dl of vitamin E, 100 micrograms/dl of vitamin A plus 1000 micrograms/dl of vitamin E, or .25 micrograms/dl of beta-carotene plus 1000 micrograms/dl of vitamin E. Macrophage bactericidal activity improved with supplementation of vitamins A plus E compared with supplementation of beta-carotene plus E or vitamin E at wk 3. Neutrophil bactericidal activity decreased with all vitamin E treatments at wk 3 and with vitamins E or A plus E at wk 6. Neutrophil phagocytosis improved at wk 3 with supplementations of vitamins A, E, and A plus E. The chemotactic index improved with beta-carotene and vitamin E compared with vitamin E alone at wk 3 and at wk 6 with vitamin E compared with vitamin A and control treatments. Retinol content of neutrophils varied at wk 3, but, by wk 6, cells supplemented with vitamins A, E, or A plus E had greater retinol concentrations than control cells. Neutrophil alpha-tocopherol concentrations at wk 3 increased from those of controls with supplementation of vitamin E or beta-carotene and vitamin E, but, at wk 6, vitamin E-supplemented cells were different only from vitamin A-supplemented cells. These data suggest that optimal plasma concentrations of vitamins A and E exist for leukocyte function.

Effects of vitamin E and selenium on immune responses of peripheral blood, colostrum, and milk leukocytes of sows.

This study was designed to assess how dietary vitamin E (E) and (or) selenium (Se) concentrations affect immune responses of gestating and peripartum sows. Multiparous sows (24), assigned to one of four groups at breeding, were fed ensiled, shelled corn-soybean meal-based diets without supplemental E or Se (-E-Se), with .3 mg of Se/kg (-E+Se), with 60 IU of E/kg (+E-Se), or with both supplemental E and Se (+E+Se) during gestation and to d 4 of lactation. Blood was obtained on 0, 30, 60, and 90 d of gestation and at parturition for serum E and Se assays. Lymphocytes and polymorphonuclear cells (PMN) were isolated from the blood, colostrum, and 4-d milk samples for immune studies. Compared with the control (+E+Se) diet, the -E-Se diet reduced (P < .05) the serum tocopherol and Se concentrations, the mitogenic responses of lymphocytes of peripheral blood (PBL) and colostrum (CL), the phagocytic activity of blood and colostral PMN, and the microbicidal activity of blood, colostral, and milk PMN. The -E+Se diet reduced (P < .05) the serum tocopherol concentrations, the mitogenic responses of PBL and CL, and the phagocytic activity of PBL. The +E-Se diet reduced (P < .05) serum Se concentrations and the phagocytic activity of PMN. The data indicated that E restriction depressed PBL and PMN immune functions, whereas Se restriction depressed mainly PMN function.

Iron augments macrophage-mediated killing of Brucella abortus alone and in conjunction with interferon-gamma.

Brucella abortus are Gram negative facultative intracellular bacteria, which survive and replicate in host macrophages. We have recently demonstrated that activation of macrophages with interferon-gamma increases their anti-brucella activities but does not result in elimination of intracellular brucellae. Here we demonstrate that iron-loaded macrophages have an enhanced capacity to kill or prevent replication of intracellular brucellae. Iron added bound to transferrin or as a salt, iron-nitrilotriacetate, can mediate the effect. Macrophages supplemented with iron-loaded transferrin in addition to activation with interferon-gamma can frequently eliminate the intracellular organisms by 48 hr after infection. The effect is apparent following phagocytosis of either nonopsonized or antibody-opsonized brucellae, and with both attenuated and virulent strains of B. abortus. The killing can be blocked by the hydroxyl radical scavengers mannitol and thiourea. This is consistent with the Haber-Weiss reaction, in which iron catalyzes the generation of hydroxyl radicals from hydrogen peroxide.

[The use of taktivin in experimental apical periodontitis exacerbated by a secondary immunodeficiency state]. / Primenenie taktivina pri éksperimental'nom verkhushechnom periodontite, otiagoshchennym vtorichnym immunodefitsitnym sostoianiem.

Apical periodontitis was simulated in 100 white rats with secondary immunodeficiency induced by a single total x-ray irradiation with the RUM [correction of PYM]-17 device. Nonspecific resistance of the rat body was assessed from the neutrophilic phagocytic activity, serum bactericidal activity, lysozyme and complement levels. These parameters were found reduced in the experimental animals; x-ray examinations revealed changes round the dental root apices. Daily injections of tactivin for 10 days in a dose 2-5 mg/kg b.m. resulted in elevation of the nonspecific resistance parameters, and the x-ray picture in this group of animals was the same as in intact controls; therefore, tactivin normalized the immunity system status and indirectly improved the clinical course of apical periodontitis.

Padma 28 modifies immunological functions in experimental atherosclerosis in rabbits.

The effect of Padma 28 on selected parameters of humoral and cellular immune reactions in rabbits subjected to experimental atherosclerosis was studied. The drug significantly reduced the size of atherosclerotic plaques in the aorta and restored to a varying extent the immune functions studied. The possible mechanism by which Padma 28 may exert its anti-atherosclerotic action is discussed in the scope of the immunological theory of atherosclerosis.

The effect of vitamin E on granulocyte function in patients with recurrent infections.

The influence of vit. E treatment on metabolic and bactericidal granulocyte activity in patients with recurrent infections was studied by chemiluminescence and phagocytosis assays. Vit. E serum level was significantly diminished before therapy. Six weeks supplementation with 200-300 mg/day of vit. E resulted in improvement of clinical status and normalisation of alpha-tocopherol serum level. Bactericidal activity of granulocytes was lower in patients than in the respective controls and it slightly rose after vit. E therapy. Before, therapy, patients granulocytes showed metabolic activity above or within the control range. Vit. E treatment increased, had no effect or decreased granulocyte metabolic activity, but never below the control range.

Effects of acetyl-L-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study.

Acetyl-L-carnitine (ALC), a drug for the treatment of ageing-related neuroendocrine dysfunctions, was orally administered--2 gm/day for 30 days--to 10 patients with active pulmonary tuberculosis (TBC). Lymphocyte-mediated antibacterial activity and serum levels of tumor necrosis factor (TNF)-alpha were evaluated before and after treatment, comparing the values with those of 10 TBC patients receiving placebo. Results show that by day 30, antibacterial activity remained unmodified or increased in ALC-treated subjects, while decreased in the placebo group. No influence of ALC on TNF-alpha levels was detectable. These data suggest that the host's immune responses to M. tuberculosis infection can be selectively modulated by drugs acting on the neuroendocrine axis.

[A comparative study of the immunogenicity of 2 group-B meningococcal vaccines in monkeys]. / Sravnitel'noe izuchenie immunogennosti dvukh meningokokkovykh vaktsin gruppy B na obez'ianakh.

The comparative study of two group B meningococcal vaccines manufactured in the USSR and in Cuba was made. The vaccine manufactured in the USSR contained the noncovalent compound of group B Neisseria meningitidis polysaccharide and outer membrane protein, and the Cuban vaccine contained group B N. meningitidis outer membrane proteins and group C N. meningitidis polysaccharide. The data obtained in this study indicated that both vaccines possessed immunological potency evaluated according to their capacity to stimulate the formation of bactericidal antibodies, whose level was found to increase eightfold after the immunization of monkeys in two injections. Besides, group B meningococcal vaccines did not induce the suppression of nonspecific protective activity characteristics of the body and did not stimulate the formation of autoantibodies to brain and liver tissues, which was indicative of the safety of these vaccines.

[The activation of the oxygen-dependent bactericidal system of human and rabbit monocytes by dust with different degrees of fibrogenicity]. / Issledovanie aktivatsii kislorodzavisimoi bakteritsidnoi sistemy monotsitov cheloveka i krolika pyl'iu s razlichnoi stepen'iu fibrogennosti.

Phagocytosis of quartz dusts by the monocytes of man and rabbit goes together with the stimulation of the substrate-free reduction of nitroblue tetrasolium, which reflects the activation of the cells' oxygen-depending bactericidal system. The quantity of the formasan produced increases, as compared to the control group, depending on the volume of the added dust. A less fibrogenic and cytotoxic dust of aluminum oxide causes only significant formation of formasan at the reduction of nitroblue tetrasolium. No extracellular generation of superoxide radicals and nitrogen peroxide by the cells were traced in the phagocytosis of quartz dusts by human and rabbit monocytes. The data obtained reveals a close similarity of the biochemical processes in the action of alveolar macrophages and monocytes with mineral dusts, and confirms a possibility of using the substrate-free reduction of nitroblue tetrasolium in the assessment of the hazardousness of industrial dusts.