Promoting effect of <Emphasis Type="Italic">o</Emphasis>-aminoazotoluene on hepatocarcinogenesis is accompanied by the increase in inflammatory and proliferative processes in liver tissue and decrease in the concentration of free thyroxin in the blood

o-Aminoazotoluene in noncarcinogenic doses promoted the development of liver tumors in female ICR mice induced by administration of diethylnitrosamine during early ontogeny. Severe inflammatory infiltration and proliferation of oval cells were found in liver tissue of these animals. The concentration of free thyroxin decreased in the blood. Our results supplement published data that promoters of hepatocarcinogenesis inhibit thyroid function. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 672–675, December, 2007     

Mechanism of mobilization of mesenchymal stem cell under the effect of granulocyte colony-stimulating factor

We studied the role of cell components and extracellular matrix of the microenvironment in the mechanisms of mobilization of mesenchymal bone marrow stem cells under the effect of granulocyte colony-stimulating factor in vitro and in vivo on CBA/CaLac mice. It was found that the mechanisms underlying the dissociation effect of granulocyte colony-stimulating factor do not include its direct effect on the interaction of precursor cells with fibronectin. The major role in this process is played by changes in functional state of stromal precursors and cell component of the microenvironment induced by granulocytic colony-stimulating factor and mediated by regulatory systems of the microorganism. __________ Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 3, pp. 169–172, July, 2007     

Mechanisms of myelopoiesis stimulation with pantohematogen and granulocyte colony-stimulating factor during cytostatic myelosuppression

We compared hemopoiesis-stimulating activities of dry pantohematogen and recombinant granulocyte colony-stimulating factor under conditions of cyclophosphamide-induced myelosuppression. These preparations stimulated regeneration of bone marrow granulomonocytopoiesis by various mechanisms. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 512–515, November, 2000     

Pharmacokinetics of amixin after repeated peroral administration to mice

Pharmacokinetics of amixin was studied after repeated administration (5 days) to animals. Perorally administered amixin is characterized by high bioavailability and is present in the circulation in high concentrations for a long time. The main pharmacokinetic parameters were estimated by the method of linear regression because of slow elimination of amixin from organs and tissues. Our results indicate that repeated treatment with amixin holds much promise for the prevention and therapy of chronic diseases (particularly hepatitides). __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 661–663, December, 2005     

Melphalan in ultralow doses decreases the severity of experimental colitis in mice

We studied the effect of melphalan in ultralow doses on mice with experimental colitis induced by substitution of drinking water for 5% dextran sulfate. Daily treatment with melphalan in a dose of 0.025 mg/kg improved the general state of animals. The influence of melphalan was evaluated by quantitative clinical, pathomorphological, and laboratory parameters. Melphalan had a local and systemic antiinflammatory effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 10, pp. 418–422, October, 2006     

The triterpenoid CDDO-Me promotes hematopoietic progenitor expansion and myelopoiesis in mice

The synthetic triterpenoid CDDO-Me has been shown to directly inhibit the growth of myeloid leukemias and lends itself to a wide array of therapeutic indications, including inflammatory conditions, because of its inhibition of NF-κB. We have previously demonstrated protection from acute graft-versus-host disease after CDDO-Me administration in an allogeneic bone marrow transplantation model. In the current study, we observed that CDDO-Me promoted myelopoiesis in both naive and transplanted mice. This effect was dose dependent, as high doses of CDDO-Me inhibited myeloid growth in vitro. All lineages (granulocyte macrophage colony-forming unit, BFU-E) were promoted by CDDO-Me. We then compared the effects with granulocyte colony-stimulating factor, a known inducer of myeloid expansion and mobilization from the bone marrow. Whereas both drugs induced terminal myeloid expansion in the spleen, peripheral blood, and bone marrow, granulocyte colony-stimulating factor only induced granulocyte macrophage colony-forming unit precursors in the spleen, while CDDO-Me increased these precursors in the spleen and bone marrow. After sublethal total-body irradiation, mice pretreated with CDDO-Me further displayed an accelerated recovery of myeloid progenitors and total nucleated cells in the spleen. A similar expansion of myeloid and myeloid progenitors was noted with CDDO-Me treatment after syngeneic bone marrow transplantation. Combined, these data suggest that CDDO-Me may be of use posttransplantation to accelerate myeloid recovery in addition to the prevention of graft-versus-host disease.     

Immunocorrecting properties of GB-115 dipeptide

We studied the effects of a new dipeptide with anxiolytic activity (GB-115, N-phenylhexanoyl-glycyl-L-tryptophan amide) on parameters of the immune in intact mice and in animals with secondary immunodeficiency caused by cyclophosphamide. GB-115 in doses of 0.1–10 mg/kg stimulated phagocytic activity of peritoneal macrophages and humoral immune response in intact mice. GB-115 exhibited immunocorrecting activity in animals with secondary immunodeficiency. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 548–551, May, 2008     

Comparative study of macrophage response in mice after DNA immunization and infection with herpes simplex virus type 1

Functional activity of macrophages and intensity of T cell immune response in mice were studied after intravaginal and intraperitoneal infection with herpes simplex virus type 1 and DNA vaccination in combination with adjuvant treatment (recombinant granulocytemacrophage colony-stimulating factor and glucosaminylmuramyl dipeptide). DNA vaccination induced a virus-specific T cell immune response with no macrophagic inflammatory reaction. Infection with herpes simplex virus type 1 was accompanied by sustained inflammation, but not by the T cell immune response. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 670–673, December, 2005     

Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3αβ signals

Effects of administration of granulocyte colony-stimulating factor (G-CSF) on the regeneration of injured mammalian skeletal muscles were studied in male C57BL/6J mice. Muscle injury was induced by injection of cardiotoxin (CTX) into tibialis anterior muscles bilaterally. G-CSF was administrated for 8 consecutive days from 3 days before and 5 days after the injection. Significant decreases of wet weight and protein content were noted in the necrotic muscle with CTX injection. A large number of the regenerating fibers having central nucleus were observed 7 days after the injection. The regeneration of injured muscle was further facilitated by the G-CSF treatment. Population of Pax7-positive nuclei was increased by the G-CSF treatment at day 7. Phospho-Akt and phospho-glycogen synthase kinase 3αβ (GSK3αβ) signals were also activated by G-CSF-administrated group during the regenerative process. It was suggested that G-CSF treatment may facilitate the regeneration of injured skeletal muscles via the activation of Akt/GSK3αβ signals.     

Effect of dehydroepiandrosterone on avoidance behavior of adult male rats

We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 63–67, July, 2004 This work was supported by the Regional Social Foundation for Russian Medicine.     

Effect of cytokines (G-CSF and SCF) on stromal precursor cells

Repeated injections of hemopoietic cytokines (granulocyte colony-stimulating factor and stem-cell factor) to normal mice increase the content of bone marrow stromal precursors, which are capable of transferring hemopoietic microenvironment; cytokines have no effect on osteogenic potencies of stromal precursors. In contrast, injection of granulocyte colonystimulating factor during organization of a hemopoietic microenvironment considerably decreases the number of stromal precursors in the ectopic focus. The role of these stromal effects of cytokines in cytokine-induced mobilization of stem cells from the bone marrow into circulation remains unclear. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 204–206, February, 1998     

In vivo activation of neutrophil function in hamsters by recombinant human granulocyte colony-stimulating factor.

The in vivo effect of Escherichia coli-derived recombinant human granulocyte colony-stimulating factor on neutrophil function was studied in golden Syrian hamsters. Significant increases in superoxide generation and specific binding of N-formylmethionyl-leucyl-phenylalanine were observed in neutrophils isolated 4 h following a single subcutaneous injection of the factor (30 micrograms/kg). However, phagocytotic activity was not significantly stimulated in hamsters treated with the factor. Recombinant human granulocyte colony-stimulating factor hastened the recovery of peripheral neutrophil counts in animals made leukopenic by prior treatment with cyclophosphamide. Beginning several hours after infection, resistance to lethal infection following intraperitoneal injection of Staphylococcus aureus was increased when neutropenic animals were treated daily with the factor. This protective effect was associated with increased peritoneal neutrophil counts and a decreased incidence of positive peritoneal bacterial cultures at 24 h after the start of treatment. These results suggest that recombinant human granulocyte colony-stimulating factor may be a useful adjunct in the treatment of bacterial infections in neutropenic patients.     

Transfer of signs of aging to young mice by splenic lymphoid cells from old syngeneic donors

Single intraperitoneal injection of splenic lymphoid cells from 20-month-old mice to 2-month-old syngeneic mice (similarly as 5-day injections of purified brain extract) leads to preterm (4 months earlier than in the control) appearance of aging factor in the blood (the main sign of old age). Combined injections of brain extract and splenic lymphoid cells led to the appearance of aging factor in the blood 5 months earlier than in the control. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 100–102, July, 2007     

Effect of Thyroxin on Behavior of Mice with Inherited Difference in Predisposition to Catalepsy

We studied effects of chronic thyroxin administration (2 mg/l, for 60 days) on motor activity, anxiety and depression-like behavior in cataleptic (ASC/Icg) and non-cataleptic (AKR/J) strains of mice. No effects of thyroxin on anxiety indicators in “open field” and “light/dark” tests were revealed in mice of the strains under study. At the same time, thyroxin increased moveability in the “open field” test in AKR/J mice and produced an antidepressant effect in the “forced swimming” test in animals from ASC/Icg strain. Obtained results are indicative of the role of inherited predisposition to catalepsy in determining the sensitivity to thyroid hormones. Translated from Byulleten’ Experimental’noi Biologii I Meditsiny, Vol. 147, No. 2, pp. 177-180, February, 2009     

Study of bipathic effect of haloperidol

Parallel treatment with haloperidol and ultralow-dose haloperidol significantly increased the psychotropic neuroleptic effect of traditional doses of the drug under conditions of preliminary of simultaneous administration, which attests to a bipathic effect of this preparation. Combination of ultralow and therapeutic doses of haloperidol significantly reducted its cataleptogenic side effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 558–560, May, 2008     

Treatment with low doses of aspirin during chronic phase of experimental Chagas’ disease increases oesophageal nitrergic neuronal subpopulation in mice

Patients with Chagas’ disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas’ disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas’ disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas’ disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology.     

Comparative Study of Cytokine Content in the Plasma and Wound Exudate from Children with Severe Burns

The content of 27 cytokines was measured in blood plasma from 19 children with severe uncomplicated burns (group 1) and complicated burns (septic toxemia, toxemia, and pneumonia; group 2). Before surgical treatment (day 4 (±2) after burn), significant differences were found in the concentrations of interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, interferon-γ, MCP-1, and granulocyte colony-stimulating factor. Cytokine concentration in group 2 patients was much higher than in group 1 patients and healthy children. The concentrations of interleukin-6, interleukin-8, and MCP-1 in group 1 patients significantly surpassed the normal level. Cytokine concentration in the plasma and wound exudates and myeloperoxidase activity in wound exudates from 4 patients of group 2 were measured over 18 days after burn. The inflammatory response was characterized by an increase in the content of interleukin-1β, interleukin-8, MCP-1, tumor necrosis factor-α, MIP-1α, and granulocyte-macrophage colony-stimulating factor in the wound (as compared to that in the plasma). Activity of myeloperoxidase in all patients was shown to correlate with the amount of MIP-1α (r=0.47), tumor necrosis factor-α (r=0.47), and granulocyte-macrophage colony-stimulating factor (r=0.55, p<0.05). Interleukin-8 concentration was beyond the limits of calibration. No correlation was found between the concentration of any of 27 cytokines in blood plasma and exudate. Our results indicate that during active surgical treatment, the wound serves as the source of inflammatory cytokines. Cytokines play a role in the systemic response and increase the degree of local inflammation, which modulates the number and activity of wound neutrophils.     

脊髓损伤后运动功能恢复中粒细胞集落刺激因子的作用

背景：近期有文献报道了粒细胞集落刺激因子在脑梗死模型及急性脊髓损伤模型中的神经保护作用,但应用的动物模型均非击打模型,与人体脊髓损伤的病理生理过程存在一定差距。 目的：观察粒细胞集落刺激因子对Allen’s脊髓损伤大鼠模型运动功能恢复的影响。 方法：使用改良Allen’s法制作T10节段Wistar大鼠脊髓损伤撞击模型,随机分为2组,粒细胞集落刺激因子组应用粒细胞集落刺激因子治疗,vehicle组注射等剂量PBS。于造模后第1,7,14,21,28,35天分别应用BBB运动功能评分法和Rivlin斜板实验评估大鼠运动功能,造模后第7,14,21,28,35天使用网格步行实验评估大鼠四肢肌力。 结果与结论：所有大鼠造模后均出现后肢瘫痪症状。造模后第7,14,21,28,35天粒细胞集落刺激因子组BBB运动功能评分及Rivlin斜板实验评分高于vehicle组(P < 0.05-0.01),造模后第14,21,28,35天粒细胞集落刺激因子组网格行走实验错误数低于vehicle组(P < 0.05-0.01),结果显示,粒细胞集落刺激因子治疗后大鼠运动功能及四肢肌力恢复情况均优于vehicle组。提示粒细胞集落刺激因子疗法对脊髓损伤起到了积极的治疗效果。     

Obligatory Role of Gamma Interferon for Host Survival in a Murine Model of Infection with Burkholderia pseudomallei

Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative bacterium capable of causing either acute lethal sepsis or chronic but eventually fatal disease in infected individuals. However, despite the clinical importance of this infection in areas where it is endemic, there is essentially no information on the mechanisms of protective immunity to the bacterium. We describe here a murine model of either acute or chronic infection with B. pseudomallei in Taylor Outbred (TO) mice which mimics many features of the human pathology. Intraperitoneal infection of TO mice at doses of >10(6) CFU resulted in acute septic shock and death within 2 days. In contrast, at lower doses mice were able to clear the inoculum from the liver and spleen over a 3- to 4-week period, but persistence of the organism at other sites resulted in a chronic infection of between 2 and 16 months duration which was eventually lethal in all of the animals tested. Resistance to acute infection with B. pseudomallei was absolutely dependent upon the production of gamma interferon (IFN-gamma) in vivo. Administration of neutralizing monoclonal antibody against IFN-gamma lowered the 50% lethal dose from >5 x 10(5) to ca. 2 CFU and was associated with 8,500- and 4,400-fold increases in the bacterial burdens in the liver and spleen, respectively, together with extensive destruction of lymphoid architecture in the latter organ within 48 h. Neutralization of either tumor necrosis factor alpha or interleukin-12 but not granulocyte-macrophage colony-stimulating factor, also increased susceptibility to infection in vivo. Together, these results provide the first evidence of a host protective mechanism against B. pseudomallei. The rapid production of IFN-gamma within the first day of infection determines whether the infection proceeds to an acute lethal outcome or becomes chronic.     

Level of liver fibrosis and immune status of mice of different age after heroin treatment and long abstinence

Young and middle-aged CBA mice were injected with “street” heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS-and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 678–680, December, 2005 Municipal Clinical Hospital No. 12