Verzögerte Abstoßung von Hauttransplantaten nach Injektion von Thoriumdioxyd bei Mäusen

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  • 56. Jg., Heft 6, 1969 Kurze Originalmittei lungen 33 f

    No addict ion to I was found in tests in monkeys. The anaIgesic act iv i ty of I is greatly dependent on chemical structure, since the amide of I is t0 t imes, and 4-al ly loxyphenylacetic acid is 2.5 t imes, less active in the S iegmund test.

    Antipyrelic activity was tested in rabbits rendered hyper- thermic by an int ravenous injection of antigonococeal vac- cine according to a modif ied technique of BAKER et al. [6]; compound I, at a dose of 200 mg/kg, was 4 to 5 t imes more active than aspirin, and compound II , at 50 mg/kg, com- pletely inhibited the effect of the pyrogen. In normal rabbits, the ant ipyret ic dose levels of I and I I do not induce hypo- thermia.

    Anti-inflammatory activity was determined in ad juvant - induced polyarthr i t is of the rat [7], us ing male Wistar rats (20 for each experiment) weighing 300--350 g, t reated dai ly f rom the 1st to 2 ts t day following the int radermal injection of the ad juvant . Table 2 shows I and I I to be at least as effective as pheny lbutazone (III).

    Table 2. Anti-in/lammatory activity in ad/uvant-induced poly- arthritis o/therat

    Treatment Dose Score ~ on day 21 Incidence mg/kg /day mean SE on day 21

    oral: Controls - - 6.41 -4- t.53 12/t7 I 25 0.94 ~ =~ 0.40 6/t 8 b I 100 0.93 o i 0.40 5/15 b II1 25 3.00 c ~ t. 13 8/15 I l l t00 0.83 ~ =~ 0.34 6/t2

    subcutaneous : Controls - - 6.30 -t- 1.15 18/20 11 25 2.t0 o =~ 0.55 11/20 b I I t00 1.40 c ~ 0.66 6/20 d I I I 25 2.40 e 0.7O 12/20 b I I I 100 t.35 ~ 0.42 9/20 ~

    Scoring system according to GLENN for est imat ing the importance of arthrit is; scores range from 0 to 4 according to the severity of the lesions in each paw; max imum score for one rat is thus t6. b-d Signif icantly different f rom the controls at the threshold zr = 0.05 (b); a=0.0t (c); ~ = 0.00t (a).

    In view of their very low degree of toxicity, especia!1y in non-rodent species like dogs and monkeys (daily doses up to I g/kg are perfectly tolerated by the monkey in 3-month toxic ity studies), I and I I were submit ted to clinical double- bl ind trials. In 55 pat ients, a compar ison of the analgesic act iv i ty of I (500 mg oral), codeine (30 mg oral), and a placebo showed that both drugs are signif icantly superior to the placebo (P < 0.05) and that I is more effective than codeine at the dose adopted. In osteoarthrit is, a trial on 30 pat ients treated dur ing two 7-day periods showed that 500 mg t . i .d . orally of I have the same therapeut ic efficacy as phenyl - butazone at 100 mg t . i .d , orally, wi th fewer side effects for the former. Last ly, a compar ison of the analgesic effect of I I at 500 mg i .m,, pheny lbutazone at 560 mg i.m., and placebo i .m. in 30 pat ients showed that the two drugs give equivalent pain relief and are signif icantly different from the placebo.

    Ant ipyret ic act iv i ty of I and I I has been ascertained in fever of var ious aetiologies in 14 pat ients ; marked decreases of temperature were observed in all cases.

    Received February 27, 1969

    [l] Bun-Hog, N. P., et al.: Nature 211, 752 (1966); Bnu-Ho L N. P., C. GILLET and G. LAMBELIN, Belgian Patent No 704.368 (27.9. 1967). - - [2] SI~GMUND, E., et al.: Proc. Soc. exp. Biol. N. Y. 95, 729 (t957); - - [3] KOSTER, R., eta l . : Fed. Proc. 18, 412 (i959). - - [4~ EDDY, N. B., and O. LEIMBACH: J. Pharmacol. exp. Ther. 107, 385 (t953). - - [5] RANDALL, L. O., and J. J. SELITTO: Arch. int. Pharmaeodyn. 11~, 409 (1957). - - [6] BAXER, J. A., et al.: J. Pharm. Pharmacol. ls, Suppl. 97 T ( t963) . - [7] GLENN, E, M., and J. GRAY:Am. J. Vet. Res. 26, 1180 (1965); GLENN, E. M. : ibid. 27, 339 (t966).

    Verz6gerte AbstoBung von Hauttransplantaten nach Injektion von Thoriumdioxyd bet Miiusen H. lXlOLTENIUS, S. TAN und I. KNAUF

    Pathologisches Ins t i tu t der Univers i t~t Freiburg

    Thor iumdioxyd ist ein ~-, fl- und 7-Strahler. Seine Halb- wertszeit betritgt 1,35"t0 l~ Jahre. Es wird nach intraven6ser In jekt ion in den Zellen des IRES gespeichert und nicht wieder ausgeschieden. Beim Mensehen verursacht es SchSdigungen, darunter eine Zerst6rung des lymphat ischen Gewebes. Ob- dukf ionsbefunde zeigen jedoch immer wieder, dab diese Kranken nicht an interkurrenten Infekt ionen sterben. Es wurde daher nntersucht , ob Thor iumdioxyd zu einer ver- z6gerten Abstol3ung yon Haut t ransp lantaten angewendet werden kann, ohne dab dabei die Versuchstiere an Infekt ionen sterben. 32 ingezfichtete weibliche und m$Imliche CBA-Miiuse, 8 his 10 Wochen alt, erhielten 24 h nor der Transp lantat ion yon zwei Hautstf lcken, 0,8 his I cm 2, yon ingeztichteten weib- l ichen C 57 bl -Spendern 0,2 ml Thorotrast intraven6s. Fiir jedes Versuchst ier wurde eine unbehandel te Maus als Non- trolle verwendet. Bet allen Tieren wurde die AbstoBungszeit der Haut t rans - p lantate vom 7. Tag bet den Kontrol len auf den t 1. Tag bet den Versuchst ieren verz6gert. Dos Ergebnis wurde an vier Versuchsgruppen zu vier Zeiten reproduziert. Wir haben kein Tier durch Intox ikat ion oder Infekt ion verloren.

    Eingegangen am l t. April t969

    Membrane Potential Measurements on Fertilized Fucus Eggs F. W. BENTRUP

    Ins t i tu t far Biologic der Universit/ it Tf lbingen

    The electric potential difference across the p lasmalemma (membrane potential) of embryonic animal ceils has been measured hitherto in only few instances (cf. [t]), that of embryonic, i.e. non-vacuolated, p lant cells in apparent ly none. This communicat ion presents evidence for this potential di//erence (P. D.) on fertilized eggs of the mar ine brown alga Fucus. Fig. I shows that upon ferti l ization the Fucus egg develops a steadi ly rising P .D . , the cytop lasm becoming eIectronegative. At about 14 h after ferti l ization a stat ionary level of around -- 78 mV is reached to be mainta ined dur ing the following 8 h, while the egg is undergoing differentiat ion and eventual ly cleaving into a thal lus and a rhizoid cell. This s tudy which is going to extend to embryonic cells of other lower plants, is to hetp analyze, firstly, electric pheno- mena associated with the development of these cells [2, 3J. The knowledge of the membrane potent ia l proved to be necessary, for instance, to t reat quant i ta t ive ly the Fucus egg's morphogenet ic response to transeel lu lar electrochemical gradients [3, 4]. SecondIy, such potent ia l measurements



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    10 ?2 14 76 18 20 22 HOUR5 AFTER FERT/L/SAT/ON

    Fig. 1. Electric potential differences (P. D.) across the plasma- lemma of Fucus serratus eggs, measured at different times after fertilization. Each dot reflects the P. D. of a single egg, recorded for a time varying between 10rain and I h. Technique: Intra- and extracellularly operating glass capillaries connect via Ag/AgC1- electrodes to a Keithley 610 C Electrometer (1014 a input resistance) to feed a pen recorder. The hltracellular capillary (0.5--0.9 v tip diameter) was inserted into the egg ( m 70 a diameter) by means of a Leitz micromanipulator. The egg-bearing chamber was kept at (18 1) ~ by thermostating the microscope stage. The eggs' P. D. was measured ill artificial sea water of pH 7.9


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