Effect of Ca++ and GABA on oxidation of glutamate and glutamine by rat brain synaptosomes

Experiments in vitro showed that the addition of Ca⁺⁺ inhibits respiration of rat brain synaptosomes in the presence of glutamate and glutamine. The addition of GABA potentiates the inhibitory effect of Ca⁺⁺ on the oxidation of glutamine but not of glutamate. GABA itself has no effect on the oxidation of either glutamate or glutamine.Laboratory of Functional Neurochemistry, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 293–295, September, 1978.     

Human T-lymphocyte subset production of immune (γ) interferon

Human T, T, and T lymphocyte subpopulations have the capacity to respond to phytohemagglutinin (PHA)in vitro with proliferation and the production of a pH 2 and heat-labile interferon. This occurs both when the subsets are isolated by direct rosetting techniques or by negative selection. Macrophages enhance the production of the interferon by each lymphocyte subset and do not themselves produce interferon in response to products of PHA-activated lymphocyte subsets. Thus our studies indicate that subpopulations of T lymphocytes known to differ with regard to morphology, surface receptors, RNA content, response to corticosteroids and X-irradiation, and other functional capabilities do not differ with regard to their capacity to produce interferon.     

Interferon β1a Treatment Modulates TH1 Expression in γδ + T Cells from Relapsing-Remitting Multiple Sclerosis Patients

A paradigm exists that multiple sclerosis is causally related to dysregulation of T_H1 inflammatory cytokines and T_H2 antiinflammatory cytokines. The cytokine source(s) that initiate the imbalances are unknown. In this study, , CD4, and CD8 T cell receptor-positive (TCR+) cells were isolated from the blood of 26 definitive relapsing-remitting multiple sclerosis patients prior to interferon -1a (IFN1a) therapy and following 8–10 weeks of this therapy. The bioactivities of interferon (IFN), interleukin 10 (IL10), and interleukin 12 (IL12) were determined. The concentrations of IFN, IL10, and IL12 from each cell type did not change significantly with IFN1a treatment. The IL10 secreted by TCR+ cells strongly correlated with the IL12 secreted by the same TCR+ cells, supporting the paradigm. Furthermore, IFN1a therapy decreased the TCR+ cell secretion of T_H1 cytokines after 8–10 weeks of therapy.     

Study on Myeloperoxidase Role in Antituberculous Defense in the Context of Cytokine Activation

Myeloperoxidase (MPO), next to the NO synthase2 (NOS2), and NADPH oxidase, is the key enzyme of the oxidative burst responsible for the antimicrobial immunity. Because MPO participates in the eradication of Mycobacterium tuberculosis in the in vitro model and the extracellular enzyme may activate cells to cytokine synthesis, we investigated the changes in the enzyme concentration in serum of patients with active pulmonary tuberculosis (TB) and correlations between MPO and TNF-alpha, IFN-gamma, and IL-12. To our knowledge, our study is the first to indicate the involvement of MPO during active TB which manifested itself in the significant increase in serum concentration. The statistically significant elevation of TNF-alpha and IL-12 was also noticed in serum of the TB positive group. The statistical analysis revealed no correlation between the cytokine and MPO production in the studied cases. However, the increase in TNF-alpha and IL-12 serum concentration with simultaneous elevation of serum MPO in the group of the highest enzyme concentration may imply that correlation between the enzyme and the cytokines should not be excluded. Our study suggests possible involvement of MPO in the antituberculous, immunological response, and implies its connection with TNF-alpha and IL-12 activation.     

Development of traumatic shock accompanied by increased activity of polyspecific antibodies reacting with DNA and endotoxins

Department of Radiation Biochemistry, Research Institute of Medical Radiology, Academy of Medical Sciences of the USSR, Obninsk. Central Research Laboratory, Rostov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Nasonova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 5, pp. 538–539, May, 1991.     

Role of adrenergic structures in functional control over the cerebral circulation

An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with and adrenoblockers showed that the constrictor response of the cerebral vessels is due to excitation of -adrenergic structures and the dilator response to excitation of -adrenergic structures. A possible mechanism of these changes is postulated.Laboratory of Pathophysiology of Respiration, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 9–12, January, 1976.     

γδ T Lymphocytosis Associated with Common Variable Immunodeficiency1

We present the case of a 28-year-old Caucasian female with common variable immunodeficiency (CVID) since age 5 who had a long history of hospitalizations for unexplained fevers and pulmonary infiltrates. The patient developed mild lymphocytosis 7 months prior to our evaluation. Flow cytometry of peripheral blood revealed an expansion of T lymphocytes, mild CD4 T lymphocytopenia, and a reduced CD4/CD8 ratio (0.2). Two subpopulations of T lymphocytes were found (CD3⁺/CD4^–/CD8⁺, 47%; CD3⁺/CD4^–/CD8^–, 53%), the vast majority of which expressed V-1. An infectious cause for the patient's T lymphocytosis could not be found. The sputum was chronically colonized with Staphylococcus aureus, and the organism produced TSST-1 in vitro. A bronchoalveolar lavage (BAL) revealed marked lymphocytosis, but T lymphocytes were not overrepresented in the BAL. Lymphocyte functional studies revealed poor proliferative responses to mitogens and staphylococcal superantigens and diminished cytokine production. V-1 T lymphocytes from the patient's blood were not expanded in vitro in response to staphylococcal superantigens. TCR gene rearrangement studies confirmed the presence of J and J1 clonal rearrangements accounting for only a small subpopulation of the T lymphocytes. These studies were repeated 5 months later and were unchanged. A bone marrow biopsy was negative for leukemia. Hence, the cause of the patient's T lymphocytosis could not be determined despite evaluation for underlying malignancy, occult infection, or superantigen-driven stimulation. The patient ultimately died of progressive respiratory insufficiency. The state of current knowledge regarding T lymphocytosis, decreased production of T lymphocytes, and a low CD4/CD8 ratio in association with CVID is discussed.     

Activation of sodium channels is not essential for endothelin induced vasoconstriction

The role of sodium and calcium ions in the vasconstrictor response of isolated rat aorta and portal vein to synthetically prepared endothelin is investigated. Contractile responses to endothelin, unlike those induced by the sodium channel activator veratridine, are unaffected by tetrodotoxin or by the removal of sodium chloride from the solution bathing the tissue. The responses are the same whether sodium chloride is replaced iso-osmotically with either sucrose or potassium chloride. The endothelin responses in all media are entirely dependent on the presence of extracellular calcium, and can be blocked by 1 M nitrendipine. These findings offer no support to the idea that voltage activated sodium channels are the primary site of action of endothelin as suggested by sequence homologies to scorpion -toxins, but are entirely consistent with the possibility that the site of action of endothelin is closely coupled to the calcium channel (Yanagisawaet al, 1988).     

Effect of preliminary pharmacotherapy on the course of acute myocardial ischemia in dogs

In dogs with acute myocardial ischemia the most complete mobilization of glycogen and the most complete and effective utilization of its breakdown products are observed after preliminary treatment with izatin, and not of -hydroxybutyric acid (GHBA) and gutimin. Izatin potentiates the beneficial effect of GHBA on the energy metabolism of the myocardium.Professorial Surgical Clinic, Department of Experimental Surgery, and Department of Morphology, Central Research Laboratory, I. P. Pavlov First Leningrad Medical Institute, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR F. G. Ublov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 429–432, May, 1979.     

Alleviation of stress and gastric ulceration by gamma-hydroxybutyric acid

The effect of preliminary administration of sodium hydroxybutyrate (GHBA) on activation of the adrenergic and pituitary-adrenal systems during emotional-pain stress and on the severity of gastric ulcers after the end of such stress was studied in experiments on rats. Preliminary administration of GHBA was shown to restrict excitation of the systems responsible for stress and to prevent the development of ulceration of the gastric mucosa. It can be suggested that activation of the GABA-ergic inhibitory system arising during stress is the sole mechanism of limitation of the stress reaction and of prevention of stress-induced injuries.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Central Research Laboratory, Irkutsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 659–661, December, 1979.     

Action ofγ-aminobutyric acid and its phenyl derivative on central links of vascular reflexes from aortic-carotid chemo- and mechanoreptors

Experiments on decerebrate cats revealed an inhibitory effect of -aminobutyric acid (GABA; 100–200 g/kg) and its phenyl derivative, phenyl-GABA (20 mg/kg), on depressor responses of the systemic arterial pressure and on inhibition of spontaneous electrical activity in the renal nerve arising in response to excitation of the carotid sinus mechanoreceptors and afferent fibers on the sinus and depressor nerves carrying impulses from mechanoreceptors. Pressor responses of the systemic arterial pressure and electrical activity evoked in the renal nerve by stimulation of the carotid sinus chemoreceptors were intensified after administration of the same doses of GABA and phenyl-GABA. The results are interpreted from the standpoint of the depriming action of GABA and its phenyl derivative on the paramedian reticular nuclei of the medulla.Paper read at the March, 1974 Meeting of the Volgograd Scientific Society of Pharmacologists.Department of Pharmacology, Volgograd Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 4, pp. 71–75, April, 1975.     

Effect of whole-body γ-ray irradiation on the rate of steroid hormone hydroxylation by rat liver microsomes

The rate of hydroxylation of androgens was shown to be significantly reduced by -ray irradiation in doses of over 600 R. The rate of hydroxylation of estrogens showed little change. During irradiation under these conditions the content of cytochrome P-450 in the rat liver microsomes fell. The decrease in the rate of hydroxylation of steroid hormones by rat liver microsomes under the influence of whole-body -ray irradiation evidently depends on quantitative changes in cytochrome P-450.Department of Molecular Pharmacology and Radiobiology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute.(Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Pokrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 668–670, June, 1976.     

Interferon-γ for treatment of severe atopic eczema in two children

Two 4- and 5-year-old children suffering from refractory atopic dermatitis were treated with recombinant interferon- (rIFN-). rIFN- was injected at 50 g subcutaneously three times a week in the first child for 3 weeks, followed by three times 25 g in week 4. In the other child two treatment courses of 4 weeks were given after a break of 2 weeks. Therapy was well tolerated. In child one reductions in eczematous body surface and severity of lesions were observed, while no beneficial effect was seen in the other. Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. While marked immunological changes were noted during IFN- treatment, clinical benefits were not encouraging. Diminished IFN- production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN- can be recommended for therapy of pediatric atopic eczema.Abbreviations IFN- interferon- - IL interleukin     

Effect of immunization against rabies on γ-aminobutyric metabolism in the animal brain

Subcutaneous injection of fixed rabies virus into albino rats weighing 100–120 g is followed by a decrease in the-aminobytyric acid (GABA) concentration in the animals' brains. An increase in the activity of GABA--ketoglutarate transaminase also is observed in the brain tissue of animals vaccinated against rabies.Laboratory of Immunopathology, D. I. Ivanovskii Institute of Virology. Laboratory of Biochemistry, N. N. Burdenko Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician V. D. Timakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 184–185, February, 1976.