RADIOACTIVE ISOTOPE STE DIES OF THE
CONNECTION BETWEEN THE LYMPH CIRCULATION
OF THE NASAL MUCOSA, THE CRANIAL CAVITY
AND CEREBROSPINAL FLUID
By
Á . O ro sz,
I.
F
öldes,
Cs. K
o sa
and
G.
T óth
IN S T IT U T E O F ANATOM Y, HISTOLOGY A N D EM B R Y O L O G Y , M ED ICAL U N IV E R S IT Y , D E B R E C E N ,
an d IN S T IT U T E O F PHY SICA L C H EM IST R Y , K O SSU TH LA JO S U N IV E R S IT Y , D E B R E C E N
(R eceived M ay 26, 1956)
I n an e a rlie r w o rk it h a s been sh o w n b y d y e tech n iq u es (C hina in k , try p a n e
b lu e , m e th y le n e blue) t h a t a ly m p h a tic c o m m u n icatio n e x ists b etw e e n th e
m u co sa o f th e n a s a l se p tu m a n d th e c ra n ia l c a v ity , in asm u ch as th e ly m p h
flo w ed fro m th e m id d le a n d p o ste rio r th ir d s o f th e se p ta l m ucosa to w a rd th e
c ra n ia l c a v ity . I n t h a t w ork e v id en ce w as o b ta in e d show ing t h a t th e dye
re a c h e d n o t o n ly th e su b a ra c h n o id a l sp ace, b u t also th e h y p o th a la m u s a n d
in th is w a y c o n trib u te d as y e t u n d e sc rib e d in fo rm a tio n [1].
T h e ex isten ce o f th e co n n e c tio n h a v in g th u s b een e sta b lish e d , a new
q u a n tita tiv e m e th o d h a s been so u g h t fo r a n d fo u n d in th e use o f ra d io a c tiv e
iso to p e s.
T h e re su lts o b ta in e d being closely id e n tic a l, i t seem s t h a t th e chem ical
p ro p e rtie s o f th e ra d io a c tiv e in d ic a to r d id n o t in te rfe re decisively w ith th e
re lia b ility a n d a c c u ra c y of th e m e th o d .
W ith re g a rd to th e above p o in ts o f view , w e h a v e u sed T h o riu m В a n d
P 3a. H e v e s y [2] d e te c te d s u b s ta n tia l a m o u n ts o f P 32 in th e c e re b ral c o rte x
a f te r in tra v e n o u s in je c tio n . T o b i a s , B e r t r a n d a n d W a i n e h a v e show n th e
p re se n c e o f A u 198 in th e cereb ral c o rte x , in th e w all o f th e la te r a l v en tricle
a n d in ce re b ral b lo o d vessels a f te r in tra v e n o u s a d m in istra tio n c a rrie d o u t
u n d e r p h ysiological co n d itio n s [3]. B a k a y [4] s tu d ie d th e d is trib u tio n o f tra c e r
e le m e n ts in th e c e n tra l n erv o u s s y ste m a fte r in tra th e c a l a n d in tra v e n o u s
in je c tio n . O n th e o th e r h a n d , in th e re p o rts d ealin g w ith th e flu id circu latio n
o f th e n a s a l m u co sa to o u r b e st know led g e no m e n tio n h a s b een m a d e o f in v es­
tig a tio n s in v o lv in g th e use o f ra d io a c tiv e iso to pes.
Materials and methods
I n p a r t of th e e x p erim e n ts th e le a d iso to p e T h B h a s been used. A few te n th s m l o f
0,2 N P b (N 0 3)2 a d d e d to th e ra d io a c tiv e p re p a ra tio n h a v e been used as c a rrie r. T h e re su lts
o f th e T h B e x p erim e n ts needed no o th e r c o rre c tio n th a n th e d e d u ctio n o f th e n a tu ra l effect.
T h e t h in sam ples a b so rb ed so little o f b e ta ra y s t h a t a u to a b so rp tio n could b e ignored. T h e
re s u lts are given fo r w e ig h t u n it.
I n th e P 32 (b u ilt in to H 3P 0 4) stu d ie s th e sam ples w ere a d ju s te d to e q u a l in a c tiv e m a te ­
r ia l p e r surface u n it a n d w ere p re p are d fro m th e d ry re sid u e of single d ig este d te s t su b stan ces.
76
Â. OROSZ, I. FÖ L D E S, CS. KÓSA an d G. TÓ TH
T h u s, a u to a b so rp tio n w a s negligible. T h e a m o u n t o f ra d io a c tiv e isotope in tro d u c e d in to th e
organism w as 0,1 m C i n r a ts a n d 0,2 m C in ra b b its .
M easurem ents w e re m ad e b y m ea n s o f a n end-w indow c o u n te r tu b e , a b o u t 5 to 6 h o u rs
a fte r injection. T o e n su re a n equal g eo m etrical d is trib u tio n , th e sam ples w ere p lac ed in to
lea d en draw ers in th e le a d e n cover of th e tu b e .
T w e n ty a d u lt m a le ra b b its and 60 a d u lt m ale r a ts w ere used in th e e x p erim e n ts. T h e
so lu tio n co n ta in in g th e ra d io a c tiv e isotope w as in je c te d in to th e m iddle th ird of th e se p ta l
m u co sa, as it h a d b e e n d o n e in th e dye series. T h e p H o f th e in je c te d so lu tio n w as 6. T he
an im a ls w ere sacrificed a fte r 15, 30, 45, 60, 75, 90 a n d 120 m in u te s. T he b ra in w as d iv id e d
in to th e follow ing p a r ts : o lfacto ry lobe, fro n ta l lobe, te m p o ra l lobe, occip ital lobe, h y p o th a la ­
m u s, hypophysis, c ere b ellu m , pons a n d oblong m ed u lla. In som e cases cen tres in th e b a sa l
ganglia, corpora q u a d rig e m in a w ere also e x am in ed for a c tiv ity .
T he controls w e re giv en 0,5 m l o f th e so lu tio n c o n ta in in g th e ra d io a c tiv e iso to p e su b ­
cu ta n eo u sly , in tra v e n o u s ly , or in tra p e rito n e a lly a n d w ere sacrificed a t th e sam e tim e as th e
e x p e rim e n ta l a nim als.
Results
In b o th th e T h B ( N 0 3)2 a n d th e H 3P 320 4 series th e lab elled ion reach ed
its m a x im u m c o n c e n tra tio n in th e c e n tra l n erv o u s sy ste m 60 m in u te s follow ­
in g in je c tio n , in c o n tr a s t wdth th e in tra v e n o u s ex p e rim e n ts. T his fa c t offers
p ro o f t h a t th e ra d io a c tiv e iso to p e in je c te d in to th e n a s a l m ucosa re a c h e d th e
c e n tra l nerv o u s s y s te m th ro u g h a n o th e r ro u te a n d in s h o rte r tim e th a n a fte r
in tra v e n o u s a d m in is tr a tio n .
As to d is tr ib u tio n , i t w as re m a rk a b le t h a t in o u r ex p erim en ts th e a c tiv ity
o f th e h y p o p h y sis w a s sig n ifican tly low er th a n t h a t o f th e h y p o th a la m u s .
T h is is in sh a rp c o n tr a s t w ith w h a t H e v e s y [2] h a s o b served a fte r in tra v e n o u s
a d m in is tra tio n , w h e n 88 p e r cen t o f th e in je c te d ra d io a c tiv e iso to p e w ere
d e m o n s tra te d in t h e p itu ita r y a n d corpus p in eale. I n th is co n n ectio n reference
is m a d e to th e s tu d ie s b y B o r e l l a n d Ö r st r o m [5] in w hich co n sid erab le
a m o u n ts of th e in tra p e rito n e a lly in je c te d P 32 a c c u m u la ted in th e choroid
p le x u s a n d in th e w a ll o f th e la te r a l v e n tricles. I n o u r stu d ies w ith T hB i t wras
in te n d e d to e lu c id a te e v e n tu a l differences in to ta l b ra in a c tiv ity a fte r a d m in ­
is tr a tio n th ro u g h d iffe re n t ro u te s. T he re su lts h a v e been ta b u la te d (T able I)
T able I
D istrib u tio n o f T h B (N 0 3)2, 30 m inutes after injection
R o u te
of ad m in istratio n
Brain
Liver
muscle
discharges/min/g
N um ber of
rats
In tra n a sa l
120,3
27,6
5
S u b c u tan e o u s
59,0
223,0
3
In tra v e n o u s
67,4
294,0
3
In tra p e rito n e a l
48,0
1500,0
3
I t is obvious f ro m th e d a ta in T a b le I t h a t T h B in tro d u c e d in to th e m id d le
th ir d o f th e n a s a l m u c o s a reach ed in th e c e n tra l n e rv o u s sy stem a c o n c e n tra tio n
77
R A D IO A C TIV E ISO TO PE S T U D IE S
tw ice as h ig h as t h a t a tta in e d b y in je c tio n th ro u g h e ith e r th e in tra v e n o u s,
o r th e su b c u ta n e o u s, or th e in tra p e rito n e a l ro u te . O n th e o th e r h a n d in p a re n ­
c h y m a l o rg an s a n d d ifferen t tissu e s low levels re su lte d a f te r in tra n a s a l a d ­
m in is tra tio n a n d h ig h levels w ith th e l a tte r m e th o d s. T he re s u lts for liv er a n d
m uscle, tw o o rg an s ric h ly su p p lie d w ith b lo o d a n d th u s re p re s e n ta tiv e are
p re se n te d in T ab le I. I t sh o u ld b e a d d ed as e x p la n a tio n t h a t th e ra d io a c tiv e
in d ic a to r in je c te d in to th e n a s a l m ucosa e n te re d d ire c tly th e C SF space. B a k a y
[6] h a s re p o rte d t h a t th e ra d io a c tiv e isotope reach es th e b ra in sooner a n d in
h ig h er c o n c e n tra tio n if in je c te d in tra c y s te rn a lly .
I t h a s b een also fo u n d (B a k a y [4]) t h a t th e iso to p e a d m in iste re d i n t r a ­
cistern a lly is d e m o n stra b le a f te r 30 m in u te s th ro u g h o u t th e b ra in (ex cep t
in th e fro n ta l lobe a n d th e c a u d a l cord). T his show s t h a t th e ro u te o f th e iso to p e
a fte r n a s a l in je c tio n is so m e w h a t d ifferen t from t h a t a d m in is te re d in tra c y s te rn ­
ally.
Table II
The distribution o f intranasally injected thorium В in the brain
Animal,
No.
I .........................
и .........................
h i .........................
IV .........................
V ...........................
V I.........................
T o ta l : ............
Amount demonstrated
1
2
3
4
Discharge/gram
Discharge/minute
total
gram
29.80
8.00
1.55
58.96
98.31
M g'
0(259
0,014
0,307
07880 g
108.96
0(794
4 1.64
18.84
11.64
3 6.84
07261
07777$
0,020
0,240
8.2
5 .4
1.2
6 .6
21.4
0 ,257
0 ,2 0 0
P Ï6
0 ,347
0 ,8 2 0
28.4
15.4
14.4
22.0
80.2
07233
0,261
0,7)25
0(328
0,837“
67 .4
5 8 .4
6.6
16.4
148.8
0.222
0 ,2 6 1
0,025
0 ,3 4 9
0 ,8 5 7
10.0
56.0
3.0
13.4
82.4
0,252
0 ,2 6 4
0,028
0 ,3 0 9
0 ,8 5 4
185.4
1 62.0
38.19
154.2
l(5 Î 5
1 (5 1 8
1 0,128
ï( 8 8 0
1 1 1 , 7 /g
137,2/g
2 5 ,8 /g
9 5 ,8/g
173.6/g
9 6 ,6 /g
E /m in
122.4
gram
1 0 6 .7
298.3
1
1.
2.
3.
4.
L e ft fro n ta l lobe.
R ig h t fro n ta l lobe.
H y p o th a la m u s.
P a rie ta l, occipital lobes, cerebellum .
8 2.02
—
78
Á . OB ŐSZ, I. F Ö L D E S , CS. KÓSA and G. TÓ TH
I n o u r e x p e rim e n ts th e a c tiv ity o f th e fro n ta l lobe d ev eloped sooner
a n d w as hig h er, b e c a u se th e ra d io a c tiv e iso to p e re a c h e d th e CSF space from
th e a n te rio r scala. T h is is c o n siste n t w ith th e s ta te m e n t m ad e b y B a k a y [6 ]
t h a t th e p a rts o f th e b r a in a d ja c e n t to th e CSF space d evelop a h ig h e r a c tiv ity .
In o u r stu d ie s o n th e d is trib u tio n o f th e tra c e r in v a rio u s p a r ts o f th e
b r a in th e follow ing re s u lts w ere o b ta in e d . T he h ig h e st n u m b e r o f discharges
p e r g ram w eig h t w as fo u n d in th e h y p o th a la m u s . T h e fro n ta l lobe e x h ib ite d
a b o u t 1/3 o f th is a c tiv ity , w hile th e a c tiv ity in o th e r c e re b ral areas (as co m p ared
to t h a t in th e h y p o th a la m u s ) teas in sig n ifican t. I n th is case th e a n im als were
k ille d 20 m in u te s a f te r in je c tio n (T ab le I I ) .
To elim in ate a d s o rp tio n a n d rad io co llo id s, in a c tiv e lead w as a d d e d to
th e so lu tio n s c o n ta in in g th e ra d io a c tiv e iso to p e. In th e se e x p e rim e n ts p erform ed
in 10 r a ts i t w as fo u n d t h a t T h B a c c u m u la te d in th e h y p o th a la m ic region,
b u t considerable a m o u n ts w ere d e te c ta b le also in th e b a s a l g anglia. T his tim e th e
m e a su re m e n ts w ere m a d e 30 m in u te s a fte r in jectio n (T ab le I I I ) .
T able II I
A c tiv ity o f different p a rts o f the brain
Part of brain tested
Measured
value
F ro n ta l a n d o lfac to ry
lobes
0 ,4 7 2 g
Discharges/ minute/g
3 6 7,5
7 7 8 ,7/g
57,5
H y p o th a la m u s
B asal ganglia
T em p o ral lobe
C erebellum , oblong
m ed u lla
0 ,0 2 2 g
2 6 1 3 ,6/g
3 9 ,0
0 ,0 3 0 g
1 3 0 0 ,0/g
124,2
Ô /3 Ï3 g
3 9 6 ,8/g
84,0
1 ,2 5 0 g
6 4 ,7/g
I n th e course o f th e in v e stig a tio n s th e q u estio n aro se, w h a t changes
o c c u r a fte r in je c tio n in th e a c tiv itie s o f CSF, blood a n d b ra in a n d ho w are
th e s e c o rre la ted d u rin g th e p erio d o f o b se rv a tio n ? To e lu c id a te th is p o in t,
th e abo v e v alu es w ere follow ed u p o v er p erio d s o f fro m 15 to 120 m in u te s a fte r
in je c tio n (6 ra b b its ). T h e re su lts are p re se n te d in F ig . ] .
U n til 30 m in u te s a f te r in je c tio n th e a c tiv ity o f C SF increases steep ly ,
sh o w in g no s u b s ta n tia l a lte ra tio n d u rin g th e n e x t 2 h o u rs. T his in d ic a te s t h a t
T h B p asses slow ly fro m th e CSF in to v en o u s blood. T h e cu rv e for t o t a l b ra in
a c tiv ity increases fo r 15 to 30 m in u te s, th e n ru n s p a ra lle l (a t a low er level)
RA D IO A C TIV E IS O T O PE S T U D IE S
79
w ith CSF a c tiv ity . T he a c tiv ity o f blo o d show ed n o s u b s ta n tia l changes d u rin g
th e 1 2 0-m in u te o b se rv a tio n p erio d .
F ig . 1. A p p e ara n c e o f iso to p e T h B a fte r in je c tio n in to th e n a s a l m ucosa
1 : I n CSF; 2 : in b ra in ; 3 : in blood
To m a k e longer o b se rv a tio n possible, s im ila r ex p e rim e n ts h av e been
c a rrie d o u t w ith P 32, w ith th e difference t h a t in th e se series th e controls, to o ,
w ere te s te d fo r a c tiv ity in th e CSF a n d th e b lo o d . The re su lts are show n in
F ig . 2.
3000-j \
F ig. 2. 1 : A fte r in tra v e n o u s in je c tio n , in blood; 2 : a fte r in tra n a s a l in je c tio n , in blood;
3 : a fte r in tra n a s a l a d m in istra tio n , in CSF; 4 : a fte r in tra v e n o u s a d m in is tra tio n , in CSF
I t w as fo u n d t h a t , a fte r in tra v e n o u s in je c tio n , P 32 re a c h e d a v ery h ig h
in itia l c o n c e n tra tio n in blood a n d a fte r 12 h o u rs, a lth o u g h i t w as s u b s ta n tia lly
low er th a n th e in itia l v a lu e , th e level w as a b o u t 3 tim es as h ig h as t h a t a tta in e d
b y u sin g th e n a s a l m uco sa ro u te . A fte r risin g fo r a b o u t 3 h o u rs, th e a c tiv ity
o f CSF d e c re a sed , fa s t a t first a n d slow ly la te r .
80
Á. OROSZ, I. F Ö L D E S , CS. KÖSA and G. T Ó T H
A fte r in je c tio n in to th e n a s a l m u c o sa th e blood lev el rem ain ed low , while
th e a c tiv ity o f th e CSF w as s till a b o u t tw ice as h ig h as t h a t o b serv ed a fte r
in tra v e n o u s a d m in is tra tio n . A fte r 12 h o u rs th e CSF a c tiv ity curve b eg an to
d ecline, b u t it w as s till h ig h abo v e th e curve of C SF a c tiv ity in th e controls.
D iscussion
T he ra d io a c tiv e iso to p e e x p e rim e n ts h av e fu lly b o rne o u t th e resu lts
o b ta in e d b y d y e te c h n iq u e s. I t sh o u ld , how ever, be n o te d t h a t fo r certain
iso to p es b lo o d -b ra in b a rrie r does n o t ex ist.
I t is k n o w n fro m th e lite r a tu r e t h a t only sm all a m o u n ts of p a re n te ra lly
in tro d u c e d ra d io a c tiv e isotopes (Cu64, I 331, Cl36, S35 a n d Z n 65) were d em o n strab le
in th e b ra in [7, 8, 9, 10, 11].
I n c o n tra s t w ith th is , o u r t a b u la te d d a ta re v e a l t h a t con sid erab le p ro ­
p o rtio n s o f th e ra d io a c tiv e isotopes T h B an d P 32, resp e c tiv e ly , e n te r th e b rain
w h e n in je c te d in tra n a s a lly . T he d is trib u tio n in th e b ra in of th e ra d io a c tiv e
iso to p e in je c te d in to th e n a sa l m u c o sa is sig n ifican tly d ifferen t fro m th a t
reco v ered a fte r in tra v e n o u s a d m in is tra tio n . In te rm s o f th e a rb itra ry a c tiv ity
u n its p e r g ra m w e ig h t th e follow ing differences w ere fo u n d in th e b r a in ; T hB
in tra n a s a lly : 120,3, su b c u ta n e o u sly 59,0, in tra v e n o u sly 67,4 a n d in tra p e rito n e a lly 48,0. T h u s, th e in tr a n a s a l v a lu e w as a b o u t tw ice as high. As reg ard s
th e a c tiv itie s o f liv e r a n d m u scle, a sim ila r co m p ariso n will show th e in tr a ­
n a s a l in o c u la tio n to p ro d u ce a n a c tiv ity n o t a m o u n tin g to m ore th a n a m ere
o n e -te n th or o n e -six tie th o f t h a t p ro d u c e d b y a d m in is tra tio n b y o th e r p a re n te ra l
ro u te s.
B ra in a c tiv ity , as expressed in th e above a r b itr a r y u n its, reach es th e
p e a k a fte r 30 to 60 m in u te s, a n d b e g in s to decrease a f te r 2 h o u rs. T h e CSF
c u rv e show s a n a lm o s t p a ra lle l co u rse, w hile th e a c tiv ity in blood increases
slow ly. F ro m th is i t foliotes t h a t d u rin g th e first 2 h o u rs o f e x a m in a tio n th e
ra d io a c tiv e iso to p e c o n te n t o f th e c e re b ra l vessels m a y b e ignored w hen e v a lu a ­
tin g th e effect in th e b ra in .
I n his stu d ie s o n th e d is trib u tio n in th e c e n tra l n erv o u s sy stem o f in tra c y s te rn a lly or in tra v e n o u s ly in je c te d P 32, B a k a y [4 ] fo u n d t h a t on in tr a ­
v e n o u s a d m in is tra tio n th e h ig h e st a c tiv ity w as re a c h e d in th e p itu ita r y , while
o n in tra c y s te rn a l in je c tio n th e ra d io a c tiv e isotope a tta in e d its h ig h e st con­
c e n tra tio n in tissu es a d ja c e n t to th e a q u e d u c t a n d ch o ro id p lexus, w ith only
v e ry sm all a m o u n ts d e te c ta b le in d iffe re n t p a rts o f th e b ra in . T hese resu lts
c a n be ex p la in e d b y th e re m a rk a b ly a b u n d a n t v a sc u la risa tio n o f th e p itu ita r y
a n d com pare in te re s tin g ly w ith o u r re su lts.
In o u r in tr a n a s a l ex p e rim e n ts th e olfacto ry lobe, fro n ta l lobe, tissu es
a d ja c e n t to th e la te r a l v e n tric le a n d th e h y p o th a la m u s e x h ib ite d a stro n g
RA D IO A C TIV E IS O T O P E ST U D IE S
81
a c tiv ity . In c o n n ectio n w ith th e h y p o th a la m u s i t m a y be su g g ested t h a t in it
th e re la tiv e ly h ig h c o n c e n tra tio n o f ra d io a c tiv e isotope can b e e x p la in e d b y
th e a b u n d a n t v a s c u la r su p p ly o f t h a t a re a a n d b y absense o f a b lo o d -b rain
b a rrie r. T he h ig h a c tiv ity in th e b a s a l g an g lia m ig h t h av e also b e e n d u e to th e ir
fa v o u ra b le c irc u la tio n . In earlier in v e s tig a tio n s m ad e b y in je c tin g d y e in to th e
n a s a l m u co sa we succeeded in follow ing u p b y gross e x a m in a tio n its course
on th e cereb ral b a se to th e h y p o th a la m u s .
I n th e p re se n t s tu d y we h a v e su cceeded ag ain to prove t h a t th e bloodb ra in b a rrie r can be by -p assed in th e w a y d escribed earlier a n d to c o n trib u te
q u a n tita tiv e d a ta concerning th e d is trib u tio n in th e c e n tra l n e rv o u s sy stem
o f th e in je c te d te s t su b sta n c e s. K r o m p e c h e r e t al. [12] h av e m a d e use o f th ese
in v e stig a tio n s in th e ra p y , w hen th e y in stille d in su lin an d stre p to m y c in on
th e n a sa l m ucosa.
SU M M A R Y
T he q u a n tita tiv e d istrib u tio n in th e c e n tra l n e rv o u s sy stem of ra d io a c tiv e isotopes
(T h B a n d P 32) in je c te d in to th e n a sa l m u co sa h a s b e e n stu d ied .
I t h a s b e en fo u n d t h a t :
1. T he g re a te s t p ro p o rtio n of th e ra d io a c tiv e iso to p e th u s in tro d u c e d is a c c u m u la te d
in th e h y p o th a la m u s , w ith considerable a m o u n ts p re se n t also in th e b a sa l g a n g lia , o lfacto ry
lobe a n d fro n ta l lobe.
2. T h e p e a k o f CSF a n d b ra in a c tiv ity is a tta in e d 60 m in u te s follow ing in je c tio n .
3. T he ra d io a c tiv e isotope in je c te d in to th e n a sa l m ucosa is a b so rb ed a t a h ig h er r a te
th a n t h a t in je c te d e ith e r su b cu tan eo u sly or in tra v e n o u sly .
4. T h e a c tiv ity re a c h e d in th e b ra in a fte r th e in tra n a s a l a d m in is tra tio n su rp assed in
e v e ry case th e a c tiv ity m easured a fte r in tra v e n o u s o r su b c u tan e o u s in je c tio n . O n th e o th er
h a n d , th e p a re n c h y m a l organs show ed a c o n sid era b ly low er a c tiv ity .
5. O b serv a tio n s c o n tin u ed over p ro lo n g ed p e rio d s rev ealed t h a t th e c o n c e n tra tio n of
ra d io a c tiv e P 32 did n o t decrease in th e C SF even a s la te as 6 hours a fte r in je c tio n .
L IT E R A T U R E
1. K osa Cs., F ö l d e s I., O rosz Á. : A z o rrn y á lk a h á rty a n e d v k erin g ésén e k a k o p o n y a ­
üreggel való k a p cso la ta i. In th e p ress. (A c ta M orph. H ung.)
2. H e v e s y , G. : R a d io a ctiv e In d ica to rs. In te rsc ie n c e P u b lish ers, N ew Y o rk , L o n d o n . (1948).
3. T o b ia s , C. A ., B e r t r a n d , J . J . , W a in e , J . : C it. H evesy.
4. B a k a y , L . : A rch. N eurol. P s y c b ia t. 66, 419 (1951).
5. B o r ell , U ., O rstro m : Cit. H evesy.
6. B a k a y , L. : T h e B lood B rain B a rrie r. T h o m a s, Springfield (1955).
7. D z ie w ia t k o w s k i , D . D . : J . B iol. Chem . 161, 723 (1945).
8. M a n e r y , J . F . : A m . J . Physiol. 129, 417 (1940).
9. R e il m a n , I., Ch a ik o f f , I. Z., N o r to n , M. E . : J . B iol. Chem. 1 39, 433 (1941).
10. S c h u b e r t , G., V o g t , IL , M a u r e r , K ., R ie z l e r , W . : Cit. H evesy.
11. S h e l in e , E ., Ch a ik o f f , I. L ., J o n e s , H . B ., M o n tg o m er y , М. J . : J . B iol. Chem . 149,
139 (1943).
12. K r o m p e c h e r , S t ., F o r n e t , B ., F ö l d e s , S t ., H a d h á zy , Cs ., O rosz , Á ., K o sa , C s ., T ó th , G.,
H a n k is s , J . , F i l i p p , G., K ö v é r , В ., K e c s k é s , J . : A c ta P hysiol. H u n g . S uppl. 6, 56
(1954).
13. R u sz n y á k I., F ö l d i M., S zabó G y . : A n y iro k k erin g és élet- és k ó rta n a . A k ad ém iai
K ia d ó , B u d a p e s t. (1955).
14. S c h w ie g k , H . : K ü n stlich e R a d io a c tiv e Iso to p e . S pringer, B e rlin — G ö ttin g e n . (1953).
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