Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies]

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.     

Efferent projections of mesencephalic locomotor neurons in the cat

Efferent neuronal projections of the mesencephalic locomotor region were investigated in cats using a horseradish peroxidase retrograde axonal transport technique. It was found that neurons located within the locomotor area form ascending and descending projections to many structures of the spinal cord and the brain but that short-axon connections running to the reticular formation of the midbrain and the medulla predominate. Small numbers of long-axon fibers may merge into the locomotor strips of the medulla and the spinal cord. The locomotor regions of the two halves of the midbrain are interlinked.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 117–125, January–February, 1986.     

Effect of alkylresorcin on biological membranes during activation of lipid peroxidation

The effect of alkyl resorcin isolated from the cells of Azotobacter chroococcum and of its structural analog devoid of the alkyl chain (resorcin) on liver microsomes and brain synaptosomes of the rat as well as on rabbit skeletal muscle sarcoplasmic reticulum fragments during activation of lipid peroxidation was studied. Alkyl resorcin was shown to produce a much more potent antioxidant effect as compared with resorcin, since it inhibited lipid peroxidation in all the three types of membranes under study at much lower concentrations. Both alkyl resorcin and resorcin which inhibit lipid peroxidation prevented lipid peroxidation-induced structural-functional damages of synaptosomal and sarcoplasmic reticulum fragment membranes. Unlike resorcin, alkyl resorcin exerted an additional effect on brain synaptosomal membranes which consisted in the stabilization of barrier functions of membranes during incomplete inhibition of lipid peroxidation. The cumulative data suggest that stabilization necessitates the presence of both resorcin radical and alkyl chain in the alkyl resorcin molecule.     

Block by phencyclidine of acetylcholine and barium induced adrenal catecholamine secretion

Activation of the sympathetic system by phencyclidine (PCP) should result in catecholamine release from the adrenals. However, adrenalectomy does not reduce PCP-induced hypertension. In an attempt to rectify this inconsistency, the direct effects of PCP on the bovine adrenal medulla were examined. At (3×10^?6M), PCP reduced the acetylcholine-(ACh)-induced catecholamine release by 50%. Surprisingly, barium-induced secretion of catecholamines was also reduced by PCP. ACh-induced catecholamine release was not altered by 10^?3M 4-aminopyridine (4 AP), the potassium channel blocker. Thus, calcium antagonist actions of PCP and consequent block of catecholamine secretion from adrenal medulla may explain the lack of effect of adrenalectomy on PCP-induced hypertension. Possible contributions of calcium and/or potassium channel blockade to other manifestations of PCP overdosage are discussed.     

Characteristics of blastolysin preparations in their ability to inhibit hemagglutination caused by bacteria of the genus Lactobacillus

Anabol and blastolysin preparations obtained from L. bulgaricus may contain surface structural components of the initial strain with adhesion activity; of these, one is similar in specificity to L. casei adhesin and the other, to L. plantarum adhesin. The antigenic activity of anabol and blastolysin, evaluated in the immunodiffusion test, does not correlate with their capacity for binding the receptors of susceptible bacterial cells, determined in the Lactobacillus-induced hemagglutination inhibition test.     

Ion-dependency of the GABA-potentiating effects of benzodiazepine tranquilizers and harmane

Experiments on an isolated spinal cord of 8-15-day-old rats have shown that one of the possible mechanisms of the GABA-potentiating action of the benzodiazepine tranquilizer, chlorodiazepoxide, may be a decrease in the intraneuronal concentration of Ca2+. This is evidenced by the enhancement of the GABA-potentiating action of chlorodiazepoxide under Ca2+ deficiency in the medium and in the presence of the blockers of the voltage-dependent Ca2+ ionic channels--Mn2+ and Co2+, and by the reduction of the effect in question under Ca2+ excess in the medium and in the presence of the K+ channels blockers--tetraethylammonium and 4-aminopyridine. The GABA-potentiating action of harmane is likely to be related to the blockade of the voltage-dependent K+ channels and elevation of the intracellular concentration of Ca2+.     

Synthesis of N-quinonyltaurines

Summary.  Both 1,4-benzoquinones and 1,4-naphthoquinones were attached to the non-proteinogenic amino acid taurine to form N-quinonyl taurine derivatives. The products were formed via the direct Michael-like addition or by substitution of a good leaving group. An attempt to bridge the two moieties via an ureido spacer resulted in the formation of a bis-quinonylamino isocyanurate derivative. Preliminary MO calculations provided internal ground-state geometries and orbital coefficients of the HOMO levels in two representing taurine conjugates. Received May 6, 2002 Accepted August 13, 2002 Published online December 18, 2002 Acknowledgments This research was supported by the Israel Science Foundation founded by the Academy of Science and Humanities. We wish to thank Ms. Ethel Solomon for skilled technical help. Authors' address: Prof. Shmuel Bittner, Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel, Fax: (972)-8-6472943, E-mail: bittner@bgumail.bgu.ac.il     

Cytological mechanisms of the development of mucosal candidiasis after exposure to a steroid aerosol preparation

Mucosal candidosis was induced in CBA mice by intraoral inoculation following treatment with corticosteroid-containing aerosol (beclomethasone dipropionate). Histologically, in hormone treated mice the adherence of the pathogen to the mucosal surface was found during the first hours after inoculation. This is followed by the formation of the germ tubes and invasion in the epithelial layer. Pseudomycelial invasion in the malpighian layer is accompanied by the leukocyte response that limits the further spread of the fungal cells. In intact mice, the inoculation is not followed by the effective attachment of the fungal cells to the mucosal surface and induction of mycotic lesions. In vitro experiments have demonstrated the enhanced adherence of fungal blastospores to the epithelial cells of the hormone treated animals, that appears to be one of the mechanisms in the pathogenesis of candidosis in these animals.     

Resistivity of Red Blood Cells Against High-Intensity, Short-Duration Electric Field Pulses Induced by Chelating Agents

The interaction of human red blood cells (RBCs) with diethylenetriamine-pentaacetic acid (DTPA) or its Gd-complex (Magnevist, a widely used clinical magnetic resonance contrast agent containing free DTPA ligands) led to the following, obviously interrelated phenomena. (i) Both compounds protected erythrocytes against electrohemolysis in isotonic solutions caused by a high-intensity DC electric field pulse. (ii) The inhibition of electrohemolysis was observed only when cells were electropulsed in low-conductivity solutions. (iii) The uptake of Gd-DTPA by electropulsed RBCs was relatively low. (iv) (Gd-) DTPA reduced markedly deformability of erythrocytes, as revealed by the electrodeformation experiments using high-frequency electric fields. Taken together, the results indicate that (Gd-) DTPA produce stiffer erythrocytes that are more resistant to electric field exposure. The observed effects of the chelating agents on the mechanical properties and the electropermeabilization of RBCs must have an origin in molecular changes of the bilayer or membrane-coupled cytoskeleton, which, in turn, appear to result from an alteration of the ionic equilibrium (e.g., Ca²⁺ sequestration) in the vicinity of the cell membrane. Received: 19 January 1999/Revised: 1 April 1999     

Spontaneous cytotoxicity mediated by invertebrate mononuclear cells toward normal and malignant vertebrate targets: Inhibition by defined mono- and disaccharides

Spontaneous non-antigen-dependent cytotoxicity is displayed in vitro by mononuclear cells from molluscs, annelids, and echinoderms. The cytotoxic potential of these cells appears to be independent of prior antigenic exposure, is easily demonstrated in vitro, and is temperature dependent. The specificity of these cells may be directed at cell-surface glycoproteins on the target cell surface since a variety of defined mono- and disaccharides can block killing. The ability of sugars to block is target cell and effector cell specific. This finding is exactly analogous to our previous finding that human spontaneous monocyte-mediated cytotoxicity is blocked in a target-specific fashion by different mono- and disaccharides. These data suggest that invertebrate as well as vertebrate mononuclear cells may “recognize” targets through a series of sugar-specific “lectin-like” molecules present on the effector cell surface.