Mechanisms of leukocyte activation during the formation of leukocytic pyrogen

Actinomycin D and cyclohexamide, inhibitors of protein synthesis, inhibit the formation of endogenous pyrogen by the blood granulocytes induced by bacterial lipopolysaccharide and specific antigranulocytic serum but do not affect the secretion of pyrogen by exudate leukocytes. This shows that the inhibitors inhibit the activation phase but not the process of liberation of the pyrogen.Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 8, pp. 203–207, August, 1978.     

Formation of endogenous pyrogen by bone marrow cells

Bone marrow cells of rabbits can produce endogenous pyrogen after stimulation with bacterial lipopolysaccharide. The optimal conditions for liberation of the pyrogen are incubation of the cells in medium No. 199 with the addition of 15% homologous serum. Participation of bone marrow cells in the formation of endogenous pyrogen and in the mechanism of fever also may occur, it is suggested, in the intact organism.Department of General Pathology, Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 16–17, January, 1978.     

Conditions of preparation and mechanism of action of macrophagal pyrogen

Activation of mononuclear phagocytes by staphylococciin vitro leads to the formation of an endogenous pyrogen. The macrophagal pyrogen does not possess specific pyrogenic specificity, and on intracisternal injection sensitivity to it is enhanced by more than 100 times compared with that observed after intravenous injection. An even sharper increase in sensitivity to pyrogen was observed in animals after elevation of the body level of cyclic AMP as a result of preliminary injection of theophylline.Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. M. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 278–281, March, 1980.     

Endogenous pyrogen formation by mononuclear phagocytes

Incubation of alveolar macrophages from rabbits and of peritoneal macrophages from peritoneal washings of albino mice did not lead to liberation of endogenous pyrogen. Peritoneal macrophages obtained after intraperitoneal injection of thioglycollate, glycogen, or heterologous blood cells into mice likewise did not secrete pyrogen on incubation without additional stimulation. Macrophages isolated after intraperitoneal injection of heterologous blood cells did not possess pyrogenic activity, probably because of the long time after phagocytosis of foreign agents. The process of pyrogen formation by macrophages in these experiments may have been triggered by phagocytosis of corpuscular particles-staphylococci or heterologous blood cells-in vitro.Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 284–286, March, 1980.     

Effect of cytostatic agents on development of the febrile reaction to injection of bacterial pyrogen

The development of the febrile reaction to injection of bacterial lipopolysaccharide (pyrogenal) in rabbits after preliminary treatment with actinomycin D and cortisone was studied. This treatment did not change the reactivity of the temperature regulating centers of the rabbits to endogenous pyrogen. After intravenous injection of the bacterial pyrogen the febrile reaction, was considerably shortened, and after intracisternal injection of the pyrogen the reaction was sharply inhibited. These results indicate an important role of polymorphonuclear leukocytes and of endogenous pyrogen formation by these cells in the mechanism of fever in response to the action of bacterial pyrogen.Department of General Pathology, Institute of Experimental Medicine, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1314–1317, November, 1976.     

Stimulating action of endogenous serum pyrogen on antibody-forming cells in the spleen of rabbits immunized with corpuscular typhoid vaccine

In rabbits immunized intraperitoneally with corpuscular typhoid vaccine the endogenous serum pyrogen formed in the animals in response to parenteral injection of the bacterial lipopolysaccharide pyrogenal increased the number of antibody-forming cells in the spleen.I. I. Mechnikov Moscow Scientific-Research Institute of Vaccines and Sera, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 8, pp. 74–75, August, 1974.     

Role of bioenergetic changes in the mechanism of action of nonsteroid anti-inflammatory drugs

The anti-inflammatory action of sodium mefenamate and salicylate is manifested to a greater degree in rats with inflammation due to ovalbumin than to dextran. In ovalbumin inflammation, sodium salicylate has a stronger action than mefenamate, and this correlates with the greater decrease in the blood concentrations of ATP, NAD, NADH, and lactic acid and the more complete abolition of the uncoupling of oxidative phosphorylation in the liver mitochondria than after injection of mefenamate. It is postulated that the fall in the level of highenergy compounds by the feedback principle leads to intensification of phosphorylation, with the consequent abolition of the inflammatory disturbances. This may account for the antiinflammatory action of the preparations.Laboratory of Experimental Therapy, Research Institute of Balneology, Odessa. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Sirotinin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 436–438, April, 1976.     

The effects of salicylate on temperature regulation in the rabbit

1. A stable pyrexia has been produced in rabbits by intravenous injection of leucocyte pyrogen followed by a continuous infusion.2. Intravenous sodium salicylate, given 4 hr after the start of pyrogen infusion, induced rapid and progressive defervescence. The rate of fall of temperature was dose dependent.3. Intravenous injection of sodium salicylate had no effect on the temperature of afebrile rabbits.4. The intraventricular injection of small doses of sodium salicylate, given 4 hr after the start of a pyrogen infusion, caused a rapid, dose-dependent defervescence, but had no significant effect on the temperature of afebrile rabbits.5. Salicylates exert at least part of their antipyretic activity through an action on the central nervous system.     

Observations on the mechanism of salicylate-induced antipyresis

1. Fever has been produced in conscious rabbits, first, by injection of leucocyte pyrogen into the lateral cerebral ventricle and, second, by local cooling of the hypothalamus.2. Both intravenous and intraventricular salicylate produce antipyresis during an established fever due to intraventricular leucocyte pyrogen. This is incompatible with the hypothesis that salicylate acts by interfering with the passage of leucocyte pyrogen from the circulation into the hypothalamus.3. Intravenous sodium salicylate has no effect on the fever due to local cooling of the hypothalamus. This suggests that salicylates do not act on central or peripheral efferent pathways involved in thermoregulation.     

Regional redistribution of blood at the climax and during decline of the febrile response in rats

Fever was induced by intravenous injection of rabbit leukocytic pyrogen and also by intravenous injection of pyrogenal. Leukocytic pyrogen led to a greater rise of temperature. In all series of experiments multivariate statistical analysis revealed the predominant influence of two factors. One reflected responses leading to a relative reduction in blood volume in the brain, myocardium, lungs, and liver and to its increase in some abdominal organs, the skin, muscular and bony tissues of the limbs, abdomen, and pelvis. The other factor reflected influences aimed at the redistribution of blood chiefly from the organs and tissues of the head, neck, and thorax into the liver.Central Research Laboratory, Second Department of Internal Medicine, S. M. Kirov Leningrad Postgraduate Medical Institute. Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Keksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 533–535, November, 1979.     

Effect of the various fractions of leukocytic pyrogen on hematopoiesis

Fractionation of leukocytic pyrogen on a column of Sephadex G-75 yielded two separate fractions, one stimulating hematopoiesis, the other possessing pyrogenic activity but inhibiting hematopoiesis. The elution profile of the Sephadex G-75 column suggests that the stimulating action is a property of high-molecular-weight substances whereas the pyrogenic and inhibitory actions are properties of low-molecular-weight substances. Pyrogenic and inhibitory activities are perhaps connected with different substances. The nature of the inhibitory factor requires further study. It presumably is a substance of chalone type.Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Pathophysiological Laboratory, Central Research Institute of Hematology and Blood Transfusion, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 523–525, May, 1978.     

Role of the adenyl cyclase system in stimulation of immunogenesis by bacterial lipopolysaccharide and by endogenous serum pyrogen

Experiments on rabbits immunized intraperitoneally with corpuscular typhoid vaccine showed that after injection of the bacterial lipopolysaccharide pyrogenal (LPS) and endogenous serum pyrogen (ESP), together with theophylline, the number of antibody-forming cells in the spleen was increased. The results point to a role of the adenyl cyclase system in the mechanism of the stimulating action of LPS and ESP.I. I. Mechnikov Research Institute of Vaccines and Sera, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 575–576, May, 1976.     

Adaptation to the action of some teratogens following administration of pesticides during pregnancy

In experiments on female Wistar rats the effect of the pesticides DDT and -BHC, administered from the beginning of pregnancy, on the intensity of the teratogenic action of sodium salicylate (SS) and of benlate, a pesticide of the carbonate group, was studied. The compounds were given on the 10th and 12th days of pregnancy respectively. Preliminary administration of the pesticides was shown to weaken the teratogenic and embryotoxic action of benlate, given in a dose of 250 mg/kg, and of SS in a dose of 400 mg/kg. Under the influence of SS in a dose of 600 mg/kg preliminary injection of the pesticides reduced the postimplantation mortality of the embryos, but the number of fetuses with developmental anomalies was the same as after the isolated action of SS in the same dose.Laboratory of Toxicology of Pesticides, Institute of Nutrition, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Minkhov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 227–228, February, 1977.     

Chemical modification of human IgG as a method of demonstrating differences between properties of antibodies and natural antiglobulins (homoreactants)

Naturally arising antiglobulin factors, or homoreactants (HR) contained in preparations of human IgG are inactivated by incubation in a solution of sodium thiocyanate (3–5 M) and sodium deoxycholate (0.005 M). Staphylococcal antitoxin contained in the same human IgG preparations is resistant to the action of these reagents. The results point to differences in the structure of HR and antibodies.Laboratory of Immunochemistry, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditisiny, Vol. 88, No. 11, pp. 585–587, November, 1979.     

Characteristics of the spectrum of psychotropic activity of sodium hydroxybutyrate

It is concluded from data showing the effect of sodium hydroxybutyrate on conditioned motor defensive reflex behavior in a conflict situation, active avoidance without discriminative control in rats, and the side position test that the spectrum of psychotropic activity of the compound possesses certain qualitative distinguishing features. The action of sodium hydroxybutyrate in subnarcotic doses can be described as that of a sedative with manifestation of certain properties of neuroleptics and tranquilizers.Laboratory of Psychopharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Science of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 563–564, November, 1979.     

Antiarrhythmic and electrophysiological properties of etmozin and its diethylamino analog

The effect of the antiarrthymic drug etmozin and its diethylamino analog (DAA-etmozin) was compared in dogs with ventricular arrhythmias caused by ligation of the coronary artery. Both compounds were shown to abolish ventricular arrhythmias. However, DAA-etmozin had a more rapid and prolonged action. The electrophysiological properties of etmozin and DAA-etmozin were studied by the voltage clamp method on frog atrial trabeculae. Both compounds were shown to reduce the fast inward sodium current; DAA-etmozin had a stronger and more prolonged action.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR. Laboratory of Electrophysiology of the Heart, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byullten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 3, pp. 243–247, March, 1979.     

Hematopoietic action of high-molecular-weight fractions of leukocytic pyrogen

By fractionation of rabbit leukocytic pyrogen (LP) on a Sephadex column and by the alcohol method a nonpyrogenic protein fraction of LP was isolated. In intact rats this fraction caused stimulation of granulocytopoiesis, an increase in the proliferative activity of the granulocytes and their absolute number in bone marrow and peripheral blood, and also an increase in the number of macrocolonies in the spleen of lethally irradiated mice on account of an increase in the number of granulocyte colonies.Department of Pathological Physiology, Central Institute of Hematology and Blood Transfusion, Moscow. Department of General Pathology, Institute of Experimental Medicine, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii Meditsiny, Vol. 89. No. 2, pp. 134–137, February, 1980.     

Effect of sodium hydroxybutyrate on the ammonia content in rat muscles during physical exertion

In experiments on rats forced to swim while carrying a load, sodium hydroxybutyrate was found to have a normalizing effect on the ammonia content in the striated muscles, a biochemical indicator of physical fatigue. Whereas in control rats not receiving hydroxybutyrate swimming led to a marked (more than twofold) increase in the ammonia content in muscle tissue, in animals receiving prophylactic sodium hydroxybutyrate (one only or as a 2-week course) ammonia did not accumulate. It is suggested that by preventing the toxic effect of one of the end products of nitrogen metabolism, sodium hydroxybutyrate may alleviate the after-effects of muscular fatigue.Laboratory of Pharmacology of the Nervous System, Institute, of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 25–27, January, 1980.     

Neurospecific S-100 protein in synaptosomes of the rat cerebral cortex

A nonspecific S-100 protein was found in the composition of low-molecular-weight acid proteins from synaptosomes of the rat cerebral cortex by capillary microdisc electrophoresis in 15% polyacrylamide gel with 0.1% sodium dodecysulfate and with the aid of a highly purified marker protein. The S-100 protein accounted for 15–20% of the lowmolecular-weight acid synaptosomal proteins.Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. S. Il'in). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 164–166, February, 1976.     

Effect of furosemide and ethacrynic acid on sodium transport and potassium secretion

Like strophanthin K, ethacrynic acid increases the sodium concentration and reduces the potassium concentration in frog urinary bladder tissue, with the result that potassium secretion is reduced; furosemide does not change these concentrations. The results point to differences in the intracellular action of furosemide and ethacrynic acid.Laboratory of Evolution of the Kidney and Water-Salt Metabolism, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, 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. 84, No. 9, pp. 319–321, September, 1977.