56. Jg., Heft 6, 1969 Kurze Or ig ina lmi t t e i lungen 33 f

No addic t ion to I was found in t e s t s in monkeys . T h e anaIgesic ac t iv i ty of I is g rea t ly d e p e n d e n t on chemical s t ruc tu re , s ince t he amide of I is t0 t imes , a n d 4-a l ly loxyphenylace t ic acid is 2.5 t imes , less ac t ive in t he S i e g m u n d test .

Antipyrelic activity was t e s ted in r abb i t s rendered hype r - t h e r m i c b y an i n t r a v e n o u s in ject ion of an t igonococeal vac- cine accord ing to a modif ied t e chn i que of BAKER et al. [6]; c o m p o u n d I, a t a dose of 200 mg/kg , was 4 to 5 t imes more act ive t h a n aspir in, a n d c o m p o u n d II , a t 50 mg/kg , com- ple te ly inh ib i ted t h e effect of t he pyrogen . I n n o r m a l rabbi t s , t h e an t ipy re t i c dose levels of I and I I do no t induce hypo- t he rmia .

Anti-inflammatory activity was d e t e r m i n e d in a d j u v a n t - induced po lya r th r i t i s of t h e r a t [7], u s ing male W i s t a r ra t s (20 for each exper imen t ) weighing 300- -350 g, t r ea t ed da i ly f rom t h e 1st to 2 t s t d a y following t he i n t r a d e r m a l in ject ion of t he a d j u v a n t . Tab le 2 shows I and I I to be a t leas t as effect ive as p h e n y l b u t a z o n e (III) .

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

T r e a t m e n t Dose Score ~ on day 21 Inc idence m g / k g / d a y m e a n • 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 s y s t e m accord ing to GLENN for e s t i ma t i ng t he impor t ance of a r thr i t i s ; scores range f rom 0 to 4 according to the sever i ty of t he lesions in each paw; m a x i m u m score for one ra t is t h u s t6. b-d Signif icant ly d i f ferent f rom t h e cont ro ls a t t h e t h r e sho ld zr = 0.05 (b); a = 0 . 0 t (c); ~ = 0.00t (a).

In view of the i r ve ry low degree of toxic i ty , especia!1y in n o n - r o d e n t species l ike dogs a n d m o n k e y s (daily doses up to I g /kg are perfec t ly to le ra ted b y t he m o n k e y in 3 - m o n t h tox ic i ty s tudies) , I and I I were s u b m i t t e d to clinical double- b l ind trials. I n 55 pa t i en t s , a compar i son of t he analgesic ac t iv i ty of I (500 m g oral), codeine (30 m g oral), and a placebo showed t h a t b o t h d rugs are s igni f icant ly super ior to t h e placebo (P < 0.05) and t h a t I is more effect ive t h a n codeine a t t he dose adopted . I n os teoar thr i t i s , a t r ia l on 30 pa t i en t s t r ea ted du r ing two 7-day per iods showed t h a t 500 m g t . i . d . oral ly of I h a v e t he s a m e t he r apeu t i c eff icacy as pheny l - b u t a z o n e a t 100 m g t . i . d , orally, w i t h fewer side effects for t h e former . Las t ly , a compar i son of t h e analges ic effect of I I a t 500 m g i .m, , p h e n y l b u t a z o n e a t 560 m g i .m. , and placebo i .m. in 30 pa t i en t s showed t h a t t h e two d rugs give equ iva len t pa in relief and are s ign i f ican t ly di f ferent f rom t he placebo.

An t ipy re t i c ac t iv i ty of I a n d I I ha s been asce r t a ined in fever of va r ious aetiologies in 14 p a t i e n t s ; m a r k e d decreases of t e m p e r a t u r e were obse rved 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., e t a 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 ( t 9 6 3 ) . - [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 u n d I. KNAUF

Patho log i sches I n s t i t u t der Un ive r s i t~ t F re iburg

T h o r i u m d i o x y d is t ein ~-, fl- u n d 7-St rahler . Seine Ha lb - wer tsze i t betr i tgt 1 ,35"t0 l~ Jahre . Es wird nach i n t r aven 6 se r In j ek t ion in den Zellen des IRES gespeicher t u n d n i ch t wieder ausgeschieden. Be im Mensehen v e r u r s a c h t es SchSdigungen, d a r u n t e r eine Ze r s t6 rung des l y m p h a t i s c h e n Gewebes. Ob- duk f ionsbe funde zeigen jedoch i m m e r wieder, dab diese K r a n k e n n ich t an i n t e r k u r r e n t e n In fek t ionen s te rben . Es wurde dahe r nn t e r such t , ob T h o r i u m d i o x y d zu einer ver- z6ger ten Abstol3ung yon H a u t t r a n s p l a n t a t e n a n g e w e n d e t werden kann , ohne dab dabei die Versuchs t ie re an In fek t ionen s terben. 32 ingezf ichte te weibliche u n d m$Iml iche CBA-Miiuse, 8 his 10 W o c h e n alt, erhie l ten 24 h nor der T r a n s p l a n t a t i o n y o n zwei Hau t s t f l cken , 0,8 his I cm 2, y o n ingez t ich te ten weib- l ichen C 57 b l -Spendern 0,2 ml T h o r o t r a s t in t raven6s . Fiir jedes Versuchs t i e r wurde eine u n b e h a n d e l t e Maus als N o n - trolle verwende t . Bet allen Tieren wurde die Abs toBungsze i t der H a u t t r a n s - p l an t a t e v o m 7. Tag bet den Kont ro l len au f den t 1. Tag bet den Versuchs t i e ren verz6ger t . Dos Ergebnis w u r d e an v ier Ve r suchsg ruppen zu vier Zei ten reproduzier t . Wi r h a b e n kein Tier du rch I n t o x i k a t i o n oder In fek t ion ver loren.

Eingegangen am l t. April t969

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

I n s t i t u t fa r Biologic der Univers i t / i t Tf lb ingen

The electric po ten t ia l difference across t he p l a s m a l e m m a (membrane potential) of embryon ic an ima l ceils has been m e a s u r e d h i the r to in only few ins t ances (cf. [t]), t h a t of embryonic , i .e. non-vacuo la ted , p l an t cells in a p p a r e n t l y none. This c o m m u n i c a t i o n p re sen t s evidence for th is potential di//erence (P. D.) on fertilized eggs of t he mar ine b rown alga Fucus. Fig. I shows t h a t upon fert i l izat ion t he Fucus egg develops a s teadi ly r is ing P . D . , the c y t o p l a s m becoming eIectronegat ive. A t a b o u t 14 h a f te r fer t i l izat ion a s t a t i o n a r y level of a round -- 78 m V is reached to be m a i n t a i n e d du r in g the following 8 h, while t he egg is unde rgo ing d i f fe rent ia t ion and even tua l l y c leaving into a tha l lus and a rhizoid cell. This s t u d y which is going to ex t end to e m b r y o n i c cells of o ther lower p lan ts , is to he tp analyze , f irst ly, electric pheno- m e n a associa ted wi th t he deve lopmen t of t h e s e cells [2, 3J. The knowledge of t he m e m b r a n e po t en t i a l p roved to be necessary, for ins tance , to t r e a t q u a n t i t a t i v e l y t he Fucus egg's morphogene t i c response to t r ansee l lu l a r e lec t rochemical g rad ien ts [3, 4]. SecondIy, such po t en t i a l m e a s u r e m e n t s

0

-20

~ -40 c3

-60

-~0

- , , f ,

�9 o ~ o o

I I [ 0 2 4 6

I 8

�9 %:.

" " : ' . ' : . 2 " ' . ' " [ ~ I [ I I I

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