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FILE NAME: Chemical Abstracts (CHAB) DATE: 1963 DOC#: CHAB045 OCUMENT DESCRIPTION: Abstract Originally Published in 1963 by Wagner 13043 Chemical Abstracts 13044 Vol. 58 New York, N.Y.). Proc. Roy. Soc. Med. 55, 1000-2(1962). A review, with some new data and interpretations, of factors affecting the production and secretion of thyrotropin (I). To suppress an excessive output of I by the anterior pituitary, tri iodothyronine (XI) has pharmacol. advantages over thyroxine (III) or thyroid ext. II binds poorly with the a-globulin which binds III so that II does not raise the protein-bound iodine (PB I). The extent of suppression of pituitary I output can be evaluated by the drop in PBI or serum III. 29 references. W .C .Tobie Control of anticoagulant therapy. The use of new tests. P. A. Owren (Univ. Hosp., Oslo, Norway). Arch. Internal Med. I l l , 248-58(1963). Among lab. methods for the control of anti coagulant therapy the thrombotest (Lancet II, 754(1959)) closely reflects the concn. of Factor X in stabilized patients and is superior to the prothrombin-proconvertin method and to Quick's method. It also detects severe Factor IX deficiency. Rachel Brown See also: Pharmaceuticals, Section 30. Food additives-- antibiotics for growth promotion and feed efficiency--tylosin (Anon) 70. Antifertility substances (Bcstein) 58. Inhibition of proteolytic activity by ethyl carbamate (Kaye) 57. Biochem istry of bone and tooth formation and anticaries factor of oats (Ventura) 65. Substituted 3-thiomorpholinones (Lehr) 38. Relative thymolytic activity of synthetic corticoids using a 6-day injection assay in the adrenalectomized rat (Dorfman) 58. Synthesis of 1,2,4-benzothiadiazine 1,1-dioxides (Klosa) 38. Synthesis of glycine bis(2-chloroethyl)amide>(Bien) 44. Syn thesis of Y.A'-dialkyl-A^-aralalkyl-Y'-l-cinnolinyl (or 9-fluorenyl or 6-methyl-3-pyridazinyl or 1-phthalazinyl or 2-quinoxalinyl) ethylenediamines of potential pharmacol. interest (Chapman) 38. Compds. with potential antituberculous activity--some derivs. of 5-phenvl-2-oxazolecarboxylic acid (Sycheva) 38. Co carbohydrate complexes (Zaidi) 14. Some regularities in in fluenza virus control with synthetic drugs (Pershin) 62. Syn thesis and structure of steroidal 4-pregneno[3,2-] pyrazoles-- a novel class of potent antiinflammatory steroids (Hirschmann) 42. Renal rickets of the hyperglycinuric type, resistant to vita min D (Laberge) 66. Synthesis of thiazole derivs. of phar macol. interest--reaction of 2-aryI-4-(2-aminoethyl)thiazoles with HCOjH and HCHO (Palazzo) 38. Some analogs of imipramine (Monro) 38. Hypotensive 1,2,4-benzothiadiazines (Bierbaum) 38. Synthesis and biol. activity of 7,8-disubstituted isoalloxazines--synthesis of N mustard derivs. (Faulkner) 38. Cyclopropyl and cyclobutyl analogs of phenyl-substituted medi cinal agents (Burger) 38. New psychotropic agents--derivs. of 5-cyano- and 5-carboxamidodibenzo(a,<i]cycloheptadiene (Davis) 36. Constitution of toxol--a toxic constituent of Aplo- pappus helerophyllus (Zalkow) 37. Di-Y-substituted 2-haloethylamines--Y,Y-dialkyl(or Y-alkyi)-2-alkyl(or aryl or aryl alkyl) derivs.--synthesis, reactivity, and pharmacology (Chap man) 35. Thio derivs. of 2,3-dihydro-4Y-l,3-benzoxazin-ione--synthesis and pharmacol. properties (Teotino) 38. Sym pathetic nervous system blocking agents--derivs. of guanidine and related compds. (Short) 38. Aldehyde hydrazone derivs. in cancer chemotherapy (Wiley) 37. Benzodioxans--isopropanolamine derivs. of 1,4-benzodioxan (Rosnati) 38. Compds. re lated to carnitine--derivs. of 4-dimethylamino-3-hydroxybutyric acid (Keller) 33. Spasmolytic 1,2,5-trisubstituted pyrroles (Buu-Hoi) 37. Comparative study of rates of hydrolysis of cholinolytically active aminoalkyl esters and thio esters (Kuz netsov) 32. Synthesis and diuretic activity of 3,3-spiro-substituted hydrothiazides (Cragoe) 38. Sulfonylureas and liver damage in normal rats and rats with CCU steatosis (Cognetti) 66. 2-Substituted 2A7-l,4-benzoxazin-3(4ii)-ones (Wheeler) 38. Op tical isomers of some cholinolytic substances (Kuznetsov) 35. Syntheses in the polymyxin series--synthesis of the highly active cyclic decapeptide 7cc (Studer) 44. Actein (Panizzi) 56. Anti tumor antibiotic, cervicarcin--isolation and characterization (Okuma) 56. Physiol, active compds.--aminothiol esters of substituted acetic, chloroacetic, benzilic, and related acids (Buehler) 35. Apparent viscosity and wall-adherence of blood systems (Copley) 65. Anticancer glycoside from Citrullus colocyntkis (El Khadem) 44. Research of tumor-inhibiting compds. (Ledochowski) 37. Monosubstituted 1,3,4-oxadiazoles (Vincent) 38. Patents: 7-Alkyl ethers of chrysin (Laboratoires Laroche Navarron) 37. l-Phenyl-4-butyl-3,5-pyrazolidinedione (De champs) 38. Cysteamine orotate ( " Farnova" Instituto Bio chimico S.p.A.) 38. Phenylethanolamine derivs. (Oesterreichische Stick-stoffwerke A.-G.) 35. l-(3,4-Dihydroxyphenyl)-2aralkylaminoethanols (N. V. Philips' Gloeilampenfabrieken) 35. Dihydrodeoxystreptomycins (Ikeda) 43. Antilipemic agents (Gollin) 43. Reducing exogenous cholesterol levels in animal organisms. Nicholas R. Di Luzio (to U.S. Atomic Energy Commission). U.S. 3,081,226 (Cl. 167-55), Mar. 12, 1963; Ital. Apph Jan. 7, 1961; 4 pp. A method of reducing cholesterol in the plasma and liver by the administration of a saccharide contg. at least two glucopyranose units joined by a 1-3(3 glycosidic unit, such as glucan, larainarin, laminaribiose, or laminaritriose is claimed' Rats on an elevated cholesterol diet which were injected 5 mg. daily of zymosan (total 30 mg. dose) showed a redn. in liver ester cholesterol and an increase in liver and spleen wt. James M. Gillingham 69--TOXICOLOGY, AIR POLLUTION, AND INDUSTRIAL HYGIENE RALPH G. SMITH Protein synthesis in poisoning. II. Incorporation of glycine- 2-Cu into albumin and other protein fractions by liver slices from normal guinea pig and those injected with CCL. Masana Ogata (Univ. Med. School, Okayama, Japan). Acta Med. Okayama 16, No. 1, l-8(1962)(in English); cf. CA 57, 8841e. Normal liver slices incorporated glycine-C14(I) into albumin and liberated the newly synthesized albumin into the medium rapidly, as detd. immunologically and by paper electrophoresis. Kidney, spleen, and immunized lymph nodes do not show this incorporation into albumin. The administration.of CC1, to animals decreased the in corporation into albumin and markedly reduced incorporation into microsomes and nuclear fractions while O consumption was only slightly reduced. Since dinitrophenol (DN P) which uncouples ox idative phosphorylation also suppresses I incorporation, it is sug gested that CCU interferes with ATP formation and thereby causes suppression of protein synthesis. III. Labeling of pH 5 enzyme with glycine-Cu and inhibition by p-chloromercuribenzoate. Ibid. 9-14. Labeling of pH 5 enzyme with glycine-C14 was in hibited 32% by 10-4 mole of p-chloromercuribenzoate (PCMB) and this inhibition was reduced to 25% by addition of 2 X 10-1 mole cysteine. The pyrophosphate-adenosine triphosphate (ppjj_ATP) exchange reaction was also reduced by PCMB, the inhibition being reduced by cysteine. The results are interpreted to show that org. Hg compds. inhibit protein synthesis by in hibiting a SH enzyme which catalyzes amino acid activation. A paper-electrophoretic pattern of pH 5 enzyme showed numerous peaks. James D. Jones Relative effects of feeding hay, atmospherically contaminated by fluoride residue, normal hay plus calcium fluoride, and normal hay plus sodium fluoride to dairy heifers. James L. Shupe, M. L. Miner, Lorin E. Harris, and Delbert A. Greenwood (Utah State Univ., Logan). Am . J . Vet. Res. 23, 777-87(1962). The following feeds were allotted to 4 groups, of 4 heifers: (1) low F~ hay (10 p.p.m. of F- ), (2) contaminated high F~ hay (62 p.p.m. of F~), (3) low F - hay 4- CaF (69 p.p.m. of F - ), and (4) low F- hay + NaF (68 p.p.m . of F~). In addn., each animal was fed 2 lb. of grain daily for 588 days. The high F hay was as toxic as NaF. CaFj proved less toxic than either the F residue on the contaminated hay or the NaF. Dental fluorosis was related to the am t. and type of F compd. ingested. Rudolph Seiden Absoiption of piperazine. G. L. Corona (Univ. Pavia, Italy). Boll. Soc. Ital. Biol. Sper. 36, 1073-6(1960). The toxicity of piperazine derivs. is correlated with the rate of absorption from the intestine. Felix Saunders Effect of diphtheria torin on the hemoglobin of the rat. Elec trophoretic and chromatographic studies. L. Raimondi and L. Basso Ricci (Univ. Pavia, Italy). Boll. Soc. Ital. Biol. Sper. i i , 1184-6(1962). Rats were inoculated with 3000 units of diph- " theria toxin and sacrificed 1,2,3,5, and 10 days later. Blood was collected from the aorta. In the electrophoregram of the hemoglobin 2 fractions can be distinguished. The slow fraction starts to disappear after 24 hrs. and disappearance is complete after 48 hrs. This change is still evident after 10 days; then the electrophoregram tends to revert to normal. C h a n g e s in the chromatogram of the hemoglobin of rats treated with sublethal doses of diphtheria toxin are also described and illustrated. S. K. Fleischmann Asbestosis in experimental animals. J. C. Wagner (Council Sci. Ind. Res., Johannesburg, S. Africa). Brit. J. Irid. Med- -2 0 , 1-12(1963). Inhalation of a fine chrysotile dust contgSi(as SiO,) 44% (no quartz by x-ray diffraction). FeO 4- FeiOi 3% , and MgO 37%, caused severe pulmonary lesions in guinea: pigs, slight fibrosis (with scanty production of segmented asbestos bodies) in vervet monkeys, and no effect in rabbits. Amosit? dust contg. Si (as SiOj) 51.2% (free SiOi 7%) and Fe 24.8%> caused marked asbestosis in all 3 species in much shorter time (4 vs. 22 months in monkeys) with plentiful production of (mostly nonsegmented) asbestos bodies. An impure crocidolite dust contg. Si (as SiOi) 46% (quartz 50 10%, and crocidolite ~ 1 0 % ) and Fe 35%, caused severe disease in guinea pigs and monkeys, with marked increase of respiratory infection (probably 1963 13045 69-- Toxicology and A ir Pollution 13046 due to its high quartz content). Dust concns. ranged 30-37.6 X 103 particles/ml., with 52-58.5% <0.3 m> 29-31.8% 0.3-1.0 p, 6-11% 1.0-2.2 fi, and 1.5-9.4% >2.2 mdiam. Andrew L. Reeves Urinary -aminolevulinic acid and porphobilinogen in lead-ex posed workers. A. J. de Kretser and H. A. Waldron (Vauxhall a Motors Ltd., Luton, Engl.). Brit. J. Ind. Med. 20, 35-40 (1963). In 100 workers exposed to Pb, the correlations between urinary Pb (I), urinary 5-aminolevulinic acid (II), and urinary coproporphyrin (III) were poor. A raised I was always assocd. with raised II and III, but levels of up to 2.25 mg. II and 0.11 m g .. III/100 ml. were assocd. with I levels below the acceptable limit of 200 y/1. The latter cases may represent a manifestation of abnormal susceptibility to plumbism, where otherwise harmless amts, of Pb cause altered metabolism of heme precursors. The identification of such individuals may have prophylactic signifi cance. 22 references. Andrew L. Reeves Evaluation of exposure to nitrobenzene. J. Salmowa, J. Piotrowski, and U. Neuhorn (Inst. Ind. Med., Lodz, Poland). Brit. J. Ind. Med. 20, 41-6(1963). Atm. concns. of PhXOj (I) ranging from 5 to 30 y/1. were achieved in a chamber by heating I at const, surface area to 25-75, and 7 volunteers were exposed by inhalation without skin contact. The amts, of absorbed I were 8.4-67.6 mg. (with lung retention decreasing linearly from 87% during the 1st hr. to 73% during the 6th hr.). Urinary p-0 2NCH(OH (II) increased rapidly during exposure, and reached max. during 0-2 post-exposure hrs.; later excretion was irregular, with traces of II persisting until after 100 hrs. Conversion efficiency of I into II was, independently of the dose, 6-22 (av. 13)% in 6 subjects, and 24-37% in 3 tests of the 7th subject. The max. allowable dose of I corresponding to the threshold limit concn. is 35 m g./day. Algebraic equations are given for thecalcn. of total excretion from any single urine specimen, and of total I absorp tion from the II-excretion rate (2 specimens). Urinary p- - HjNCjHjOH was not detected. Andrew L. Reeves Fatal addiction to trichloroethylene. W. R. L. James (Natl. School Med., Cardiff, Wales). Brit. J. Ind. Med. 20, 47-9 (1963). A case report of a worker of an electroplating plant, who showed evidence of addiction to CHCLCCli (I) vapors at work. Paresis of the olfactory nerves with intermittent gastric disturb ances developed in the course of 9 years, and sudden death not preceded by severe physical exertion occurred 17 hrs. after the last known exposure. F atty degeneration of the liver and old and recent lung hemorrhages were found. I content in blood was 2.25 mg./lOO ml., in liver 7.1 mg., in stomach and contents 19.9 rag .,' and in small intestine and contents 14.9 mg. The urine contained 55.5mg.CCl3CO:H/100mi. 22 references. Andrew L. Reeves The toxicity of tetramethyilead solutions to mice and rabbits. N. Castellino, A. Rossi, and R. Mole (Univ. Naples). Brit. J. Ind. Med. 20, 63-5(1963). Mice and rabbits were given sub cutaneous injections of a Me<Pb soln. used as a gasoline additive (contg. 66.3% other ingredients, including (CHjCl)*, (CHsBr)j, and toluene dyes) (in EtOH-HjO) in doses ranging 20-1200 mg./kg., administered inO.Ol ml. vol./g. body wt. The following L.D-w's were observed in mice at various times after injection: 6 hrs., 1117-1230 (mean 1173); 3 days, 221.5-226.9 (224.1); an d ' 10 days. 19.94-43.52 (31.11) mg./kg. At 2 weeks, the mortality of controls (receiving EtOH-HjO only) was 33-60%. The mixt. was lethal to 4 rabbits in 3-6 days at 400 mg./kg. and in 18-24 hrs. at 800 mg./kg. Mice exposed to the inhalation of the mixt. (30 min., concn. 1.2-40 g./cu. m., at air flow rate of 740 l./h r.) showed L.D.m's (in g./cu. m.) of 36.4-45.8 (mean 40.8) during the 1st, and 4.14-13.36 (8.51) during the 10th day after single exposure. Hyperexcitability was the leading symptom in mice receiving >300 m g./kg.; there were no symptoms in mice receiving smaller injection doses, or inhalation doses <2 g./cu. m. It is concluded that Me<Pb has a low toxicity. Andrew L. Reeves Fixation and elimination of selenium in the course of intoxica tion in the rabbit. J. Roquebert and G. Yitte (Lab. Pharm. Chim. Pharmacodyn., Bordeaux, France). Bull. Soc. Pharm. Bordeaux 101, No. 4, 237-42(1962). In acute intoxication of selenium (I) 1.5 mg./kg. in 3 rabbits and 2 mg. I/kg. in 3 other rabbits in the form of subcutaneous injection of sodium selenite (II), I is found principally in the liver, kidneys, and lungs. In chronic intoxication in 5 rabbits receiving I, 0.200 mg./kg. daily in the form of aq. soln. of II administered through the esophagus, I is found mainly in the liver, kidneys, and spleen, but much less in the lungs than in acute cases. In prolonged intoxication, I is detectable in hair of the rabbit. On the av., 50% of the dose is eliminated in the urine. Fecal elimination is 18-22% of the administration, higher when given orally than when injected. On 3 rabbits after oral administration I of 0.20 mg. I/kg. during 1 month in the form of II, the elimination was significant during the first 8 days, but decreased progressively till it became negli gible after 30-35 days. H. Uchikawa Functional testing for behavioral toxicity: a missing dimension in experimental environmental toxicology. Joseph B. Ruffin (Univ. of Oklahoma, Norman). J. Occupational Med. 5, 117-21 (1963). A discussion of psychotoxicology and conditioned reflex evaluation. Andrew L. Reeves Thyroid influences on the toxicity of the respiratory irritant gases, ozone and nitrogen dioxide. Edward J. Fairchild, II, and Stuart L. Graham (U.S. Public Health Service Labs., Cincinnati, Ohio). J . Pharmacol. Exptl, Therap. 139, 177-84(1963). Chem. or surgical thyroidectomy significantly enhanced the survival of mice or rats exposed to otherwise Iethai concns. of the oxidizing respiratory irritants 0 3 and NO;. Conversely, in creased thyroid activity (administration of thyroid hormones) made mice highly susceptible to the action of these gases. Thy roid blocking agents given simultaneously with thyroid hormones gave no protection and augmented the toxic influence of the thy roid hormones. Use of 2,4-dinitrophenol in dosages known to elevate metabolism to supernormal levels did not significantly alter the toxic response to inhalation of Oj; evidence is given that hypermetabolic rate is not the crucial determinant of augmented toxicity shown by thyroid-treated animals, and that other factors are more likely accountable. L. E. Gilson Lipid mobilization following carbon tetrachloride administra tion. Arlene J. Maximchuk and David Rubinstein (McGill Univ., M ontreal). Can. J. Biochem. Physiol. 41, 525-8(1963). As early as 8 hrs. after intraduodenal injection (1 ml./kg. body wt.) of CC1* to rats, there is a mobilization of fatty acids, as indi cated by elevated serum free fatty acids, and much of the mo bilized free fatty acids is found in the liver as triglycerides. It is suggested th a t this increase in lipid mobilization ar.d accretion in the liver is at least partly responsible for the pathol. findings of hepatic fat infiltration. A. E. Teeri Effects of type B botulism toxin on pyruvic acid content in guinea pig tissues. Z. P. Pak (N . I. Pirogov 2nd State Med. Inst., Moscow). Farmakol. i Toksikol. 25, 614-18(1962). Colorimetric pyruvic acid assays in brain, medulla oblongata, spinal cord, muscles, and blood showed that type B botulism toxin did not change the content in the brain, caused a decrease in medulla oblongata and spinal cord, with an increase in muscles and blood. Probably a vitamin Bj deficiency is involved. Julian F. Smith Maximum permissible concentration of cyanuric acid and of its monosodium salt in water supplies. V. T. Mazaev (I. M. Sechenov 1st Med. Inst., Moscow). Gigiena i Sanit. 27, No. 12, 13-19(1962). Cyanuric acid and its Na salt are detected by taste at 6 and 25 m g ./l., resp. These limits are suggested as the max. permissible since at these concns. they do not influence the .sanitary regimen of water basins, and doses of 3 and 10 mg./kg., resp., did not affect the morphology of the blood, glycogenesis, cholinesterase activity, phagocytic activity, serum protein dis tribution, or O consumption of rats and guinea pigs during 6 months. John Howe Scott Acetaldehyde transformations la rabbits. L. M. Tsai. Gigiena Truda i Prof. Zabolevaniya 6, No. 12, 33-6(1962). Rabbits were exposed for 3 hrs. to vapors of acetaldehyde (I) in concns. of 1, 5, 10, and 20 m g./l., resp. I in blood was detd. before, 5, 20, 40, 60, 120, and 180 min. after beginning, and 2, 5, and 10 min. after interruption of inhalation. Independently of the ccncn. of I in the inhaled air, blood I concn. increased successively within the first 40 min., then the level became stabilized. After inhalation was interrupted, I blood concn. de creased very quickly, so th at 2 rain, later only traces of I could be found. In liver only within the first 5 min. after interruption were measurable am ts, of I found; later only traces were present. No increased am t. of AcOH in urine of rabbits exposed for 3-4 hrs. to I vapors a t 5-15 m g./l. was found. Thus, it is con cluded th a t I is metabolized very quickly to its end-products, C02 and HjO. J. Jelinek Acute phosphorus poisoning. J. Malcolm Cameron and Edgar Rentoul (London Hosp. Med. Coll.). Med. Sci. Law 3, 71-6(1963). Pathol, and chem. data are presented from post mortem specimens of victims, of acute P poisoning. The inci dence of fatal P poisonings in Scotland from 1881-1960 is given. A method of histol. demonstrating P in liver is described. Treat thin slices of liver for 20 min. with the following soln.: ammonium molybdate 3 g., 20 ml. 30% HC1, and 20 ml. H20 ; reduce in 0.02N HC1 for 2 min.; rinse quickly in distilled HjO; wash in 2.5% NHj for 5 min.; mount in von Apathy's watery m ount. Tissues contg. P are colored blue-green. I . Sunshine Value of antidotes in thallium poisoning. B. Gancarz. Med. Wet. (Poland) 15, 648-9(1959)(in Polish). Na2S.O,, KI, . Na*SO.<, and Na citrate were of no value as antidotes to exptl. T1 sulfate poisoning in guinea pigs and a dog. Two guinea pigs which vomited, thereby eliminating pptd. T1 salts from the stomach before absorption took place, survived. From Vet. Bull. 30, Abstr. No. 1951(1960). . . CA Cholinesterase activity and intraocular tension in tetraethyl lead-poisoned rabbits. Z. M. Skripnichenko and L. S. Zhol- nerovich. Oftal' mol. Zh. 17, No. 8, 484--90(1962). Cholines terase (I) activity in the blood of normal rabbits showed only slight fluctuations during the 30-60 days observation. The same was true of the rabbits' intraocular pressure regulation, which did not exceed 24.0 mm. in either eye over the period of