Effect of compound GB-115 on morphine-induced analgesia

Experiments on outbred mice showed that compound GB-115, a retropeptide analogue of the tetrapeptide cholecystokinin, produced a naloxone-dependent potentiating effect on morphine-induced analgesia in the hot-plate test, but did not modulate animal behavior in the tail-flick test in outbred mice. This potentiation of antinociceptive activity of morphine was probably related to the interaction of GB-115 with supraspinal opioidergic mechanisms. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 645–647, June, 2007     

Experimental study of the pharmacokinetics of a tryptophan-containing dipeptide GB-115

Pharmacokinetics of an original compound GB-115 (N-phenylhexanoylglycyltryptophan) synthesized on the basis of the structure of endogenous tetrapeptide cholecystokinin-4 was studied by means of high-performance liquid chromatography. Pharmacokinetic parameters were calculated after intravenous and peroral administration of GB-115. Our results indicate that this dipeptide is resistant to peptidases. The absolute bioavailability of GB-115 is 4.65%. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 9, pp. 285–287, September, 2007     

Effects of natural suppressor cells on production of Th1 and Th2 cytokines and proliferation of polarized T cells

Natural suppressor cells from the bone marrow of intact animals and mice with Th1-and Th2-dependent immune response largely suppressed the production of Th1 (IFN-γ, IL-2) and Th2 cytokines (IL-4). Antiproliferative activity of natural suppressor cells from intact and immunized animals was mediated by NO. Proliferation of Th1 cells was suppressed greater than that of Th2 cells. This selective effect of natural suppressor cells on the proliferation of target lymphocytes was due to higher stimulatory potential of Th1 cells (in comparison with Th2) towards natural suppressor cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 425–428, April, 2006     

Restoration of gastrocnemius muscle in mdx mice of different age after injury and implantation of xenogenic muscle tissue

The intensity of regeneration of crossed gastrocnemius muscle was evaluated in two groups of mdx mice of different age 2 weeks after implantation of crushed muscle tissue from newborn rats into the wound defect area. The effect of xenoplasty manifested in increased weight of the damaged muscle. The effect was observed in mice aging 12–16 weeks but not in those aged 40–48-weeks. Structural changes in the skeletal muscle tissue intrinsic of mdx mice and augmenting with age were detected in intact mice before the experiment. Activity of muscle fiber regeneration in intact and injured muscle of 40–48-week-old mice was significantly lower than in 12–16-week-old ones. Myoblasts of the xenogenic transplant retained viability in recipient muscles for at least 2 weeks. Post-traumatic regeneration was stimulated in only 12–16-week animals. Xenoplasty was ineffective in older animals and even somewhat enhanced the destructive processes in the muscle. It seems that age-specific regeneration activity of the recipient skeletal muscle tissue should be taken into consideration in the development of effective strategy of cell therapy for progressive muscular dystrophy. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 8, pp. 216–220, August, 2006     

Immunopharmacological properties of noopept

Noopept, a peptide analog of piracetam, enhanced phagocytic activity of mouse peritoneal macrophages, stimulated humoral and cellular immune response to various antigens, and markedly increased spontaneous proliferative activity of splenocytes. In animals with secondary immune deficiency caused by cyclophosphamide, noopept exhibited immunocorrector properties. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 54–57, July, 2007     

Effect of lactate on functional activity of macrophages under normal conditions and during tumor growth

Lactate modulated functional activity of macrophages from intact mice and animals with transplantable syngeneic hepatoma 22a. Sodium lactate in a concentration of 6.5 mM in vitro increased functional activity of resident peritoneal macrophages from intact mice. The growth of transplantable syngeneic hepatoma 22a was associated with the absence of correlation between nitrite synthesis by peritoneal macrophages and serum lactate concentration. Therefore, this agent cannot be considered as a systemic activator of macrophages. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 72–75, January, 2006     

GABA in regulation of communicative activity and sexual motivation of male mice with different psychoemotional status

We studied the effects of drugs modulating GABA content in the brain on communicative activity and sexual motivation of male mice. The effects of the drug depended on animal genotype and initial psychoemotional status. Aminooxyacetic acid elevating GABA content did not modulate communicative activity of intact males, reduced it in aggressive animals, restored in anxious animals, and promoted exhaustion of sexual motivation in anxious animals. Thiosemicarbazide reducing GABA level produced an anxiogenic effect and destabilized sexual motivation in intact males. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 186–192, February, 2007     

N-methyl-D-aspartate receptors and amnesia in mice with depression-like state

We studied the effect of activation (N-methyl-D-aspartic acid and D-cycloserine) and blockade (dizocilpine and 7-chlorokynurenic acid) of N-methyl-D-aspartate receptors on the development of amnesia in intact and depressive mice under conditions of conditioned passive avoidance response. Agonists and antagonists of N-methyl-D-aspartate receptors produce a strong antiamnesic effect in mice with behavioral despair. In intact animals, only N-methyl-D-aspartic acid and D-cycloserine improved passive avoidance performance. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 484–486, November, 2007     

Effect of trekrezan on immunogenesis under experimental conditions

We studied the dynamics of immune reactions to trekrezan in mouse pups after vaccination of adult mice during pregnancy and mouse pups at different terms after birth withSalmonella typhimurium 34–96. The preparation modulated activity of the immune system and stimulated antibody production in the pre- and postnatal period. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 196–197, August, 2004     

Regeneration of the spleen in intact animals and radiation chimeras

Regeneration of the splenic tissue after partial splenectomy is incomplete in adult non-irradiated mice and lethally irradiated animals reconstituted with donor syngeneic bone marrow. Transplantation of the splenic tissue to intact adult animals after partial splenectomy resulted in virtually complete regeneration of the spleen. In chimeras recovery of the splenic tissue was decreased; autotransplantation of the whole spleen or its part did not lead to appreciable changes in the weight and cellularity of this organ. No more than 30% splenic tissue is restored after complete splenectomy and transplantation of the splenic tissue in intact and chimeric mice. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 348–350, September, 2004     

Diurnal dynamics of cytokine spectrum produced by immunocompetent cells of intact mice

The production of cytokines by immunocompetent cells of intact mice was studied in various phases of the diurnal cycle. The ratio of produced cytokines was shown to differ in various phases of the diurnal cycle. The correlation between spontaneous production of various cytokines disappeared at 20:00, which reflects the development of physiological immunosuppression due to evening increase in physical activity of mice and corresponding changes in neuroendocrine status. Our results illustrate the existence of diurnal variations in intercellular interactions in the immune system. These data should be taken into account in the study of the mechanisms for cytokine immunoregulation and development of new schemes for cytokine immunocorrection. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 10, pp. 448–451, October, 2007     

Cytotoxic activity of lymphocytes isolated from mouse liver involved into tumor process

We studied cytotoxic activity and immunophenotype of mononuclear cells isolated from the liver of mice after implantation of ovarian cancer cells into the liver parenchyma. The isolated cells exhibited higher natural killer cell activity and possessed higher cytotoxic potential against autologous tumor cells compared to spleen lymphocytes. The ratio of CD3⁺ lymphocytes and natural killer cells was high in the liver with tumor metastases. Lymphoid cells were practically absent in the liver of intact animals. Natural killer cells and T cells from liver tumor tissue play an important role in antitumor immunity and can be used for local and regional adjuvant immunotherapy of liver metastases. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 76–79, January, 2006     

Effects of Succinic and Glutamic Acid Combination on Energy Metabolism in the Liver of Mice under Conditions of Hypoxia

Treatment of mice by a combination of succinic and glutamic acids prevented the metabolic disorders in the liver under conditions of normobaric hypoxia. In addition, the activity of the mitochondrial fast metabolic cluster remained intact and lipid peroxidation was limited. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 307–310, March, 2009     

Generation of free oxygen radicals and clastogenesis in bone marrow cells in MRL/1 mice

The level of chemiluminescence induced by phorbol myristate acetate or opsonized zymosan in the bone marrow cells of 5–6-month-old male MRL/1 mice is significantly higher than that in the same cells of 1–2-month-old mice. The number of chromosome aberrations induced by the prooxidant mutagen dioxydine in bone marrow cellsin vivo is significantly higher in 5–6-month-old MRL/1 mice than in 1–2-month-old mice. It is suggested that these effects are more pronounced in 5–6-month-old animals due to progressive development of rheumatic pathology in this mouse strain. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 22–25, January, 1997     

Testosterone and behavior: Involvement of the hormone in psychotropic effects of baclofen

We studied the effect of baclofen (GABA_B receptor agonist) on the behavior of male mice with different levels of anxiety in tests for social and sexual contact and on blood testosterone levels. The drug reduced testosterone level and behavioral reaction to an unknown male in intact animals and did not modulate the hormone level and social contacts in anxious mice. In the test with receptive female, baclofen reduced testosterone level and sexual motivation in intact males and did not modulate the hormone level and initial sexual interest in anxious mice. Parallelism in the development of behavioral and endocrine components of the reaction to social and sexual stimuli confirms possible involvement of testosterone in psychotropic effects of baclofen. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 222–226, February, 2007     

Orientation and exploratory behavior and anxiety of CBA mice with anosmia induced by N-trimethylindole (skatole)

The behavior of CBA mice in the hole-board test and elevated plus maze was studied after intraperitoneal injection of skatole leading to destruction of the epithelium in the main olfactory system. Locomotor and exploratory activity and degree of anxieties were low in intact mice. Anosmia was accompanied by an increase in orientation and exploratory activities and degree of anxiety. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 4–7, January, 2007     

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     

Number of Stromal Precursors in Mouse Bone Marrow and Expression of Cytokine Genes in Primary Cultures of Mouse Bone Marrow Cells during Various Periods after Immunization with <Emphasis Type="Italic">S. typhimurium</Emphasis> Antigens

Administration of S. typhimurium microbial mass to mice was followed by a significant increase (by 3–4 times) in the efficiency of cloning and number of stromal precursors in the femoral bone marrow. These parameters were maximum on days 1–3, but returned to normal by the 8th–15th day after immunization. As differentiated from intact animals, the expression of genes for proinflammatory cytokines IL-1β (day 1 after immunization), IL-6 (days 1–3), TNF-α (days 1, 3, and 6), and IFN-α (days 1–3) was detected in bone marrow cultures from immunized mice. The expression of genes for IFN-γ, IL-18, and IFN-α was decreased on days 1, 3, and 6 after immunization of animals, respectively. Gene expression for the antiinflammatory cytokine IL-4 was observed on day 6 after immunization. Therefore, this system was not characterized by a decrease in the immune response of stromal cells. The stromal component of hemopoietic and lymphoid organs has the vector of influences in response to bacterial antigens. This vector is directed to the stimulation and progression, but not to the suppression of immune reactions. Our results indicate that resident stromal cells play a role in the immune response of the body.     

Parasympathetic cardiac effects in sympathectomized rats

In adult sympathectomized rats the right and left vagus nerves exhibited asymmetric effects on heart rate and strength of cardiac contractions. After vagotomy, the heart rate and stroke volume remained high in sympathectomized rats, but returned to normal in intact animals. The sympathetic nervous system plays a role in postvagotomic tachycardia. Sympathectomized rats were characterized by higher reactivity of cardiac β-adrenoceptors to propranolol compared to intact animals. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 8, pp. 131–134, August, 2007     

Combined disorders in erythro- and immunopoiesis in (C57Bl/6xDBA/2)F1 mice with immunodeficiency induced by graft-versus-host reaction and immunocomplex glomerulonephritis

Disorders in erythro-and immunopoiesis were studied in B6D2F1 mice with immunodeficiency induced by graft versus host reaction and with immunocomplex glomerulonephritis. By the 6th–7th months of the disease the animals developed anemia accompanied by enchanced phagocytic activity of macrophages and production of tumor necrosis factor. Macrophage dysfunction is presumed to be a cause of anemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 448–451, April, 2000