Metabolic effects of neopyrithiamine and the aneurin contents in the tissues of the rat

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  • 140 Br~ves communications - Brevi comunicazioni [EXPERIENTIA VOL. X/3]

    en accord parfa i t avec les calculs 6tablis par CARR 1 sur des bases toutes diff6rentes.

    ,

    b . , %. ... qk*

    Fig. 5a. Portion cytoplasmique d'une cellule sarcomateuse trait6e h l'alcool C 14. Presence de nombreuses colonies de corpuscules dont quelques-unes prennent l'aspect de v6ritables corps d'inclusion qui paraissent se constituer ~ partir de masses tr~s denses et homog~nes.

    Grossissement 11000 . Fig. 5 b. Dessin du mSme endroit destin~ ~ mieux montrer la struc- ture fine des corps denses, visibles seulement par transparence sur

    le clieh~ original.

    2 Que les corpuscules-virus en vole de format ion peuvent prendre l 'apparence de corps d' inclusion ou d '6bauches de figures cristalloides, comparables t~ celles mises en 6vidence par WYCKOFF 2 dans certains bact6rio- phages et autres virus.

    Nous tenons ~. exprimer notre reconnaissance A Mme LIsE DUGIED et A Mlle HENRIETTE GOARI~GUER pour leur collaboration technique qui nous a 6t6 tr~s pr6cieuse.

    CH. OBERLING, W. BERNHARD, Mme A. DONTCHEFF et P. VIGIER

    Institut de Recherches sur le Cancer, Ville]ui[ (Seine), France, le 11 aoC, t 1953.

    Zusammen/assung

    In vitro geztichtete Zellen des Rous 'schen Sarkoms wurden der Wi rkung von R6ntgenst rah len und radio- akt ivem Alkohol (CH3CI*H,OH) ausgesetzt und darauf e lektronenopt isch untersucht . In e inem geringen Pro- zentsatz der untersuchten Ku l turen (9,5%) konnten virusart ige Part ike lchen von 60 bis 90 m/* Durchmesser intra- oder extrazellulttr dargestel l t werden, die mit den Yon CLAUDE, PORTER und PICKELS gefundenen ident isch sind und wahrschein l ich dem Rousschen Virus zugeord- net werden k6nnen. Es wurden Kolonien von solchen Gebi lden in t razytop lasmat isch in Form von Einschluss- k6rperchen beobachtet . Auch unbest rah l te Kontro l len

    1 j. G. CARR, Proc. Roy. Soc. (Edinburgh [B] 62, '247 [1947]). 2 R. W. G. WYCKOFF, Presse m~dicale 58, n 82, 25 d~cembre

    1950. Article dans ((Science in Progress~ [7], Ed. Baitsell, Yale Uni- versity Press 1952.

    yon Sarkomzel len wiesen Vi rusk6rperchen auf, wenn auch bisher in ger ingerem Prozentsatz .

    Es ist vorderhand noch unsicher, ob der Bestrah lung eine primttre Rolle in der Darste l lbarke i t dieser Viren zukommt.

    Metabo l i c Ef fects of Neopyr i th iamine and the Aneur in Contents in the T i ssues of the Rat

    In earl ier researches 1 on the metabol ic a l terat ions produced in the rat t reated wi th Neopyr i th iamine (N.P.), we observed an increase in the blood pyruvate , decrease of the R.Q. and a decrease in the energet ic metabo l i sm (H.P.) of the same ent i ty as demonst ra ted by rats on an aneur in-depr ived diet (3-4 weeks); a more marked d iminut ion of muscular glycogen, and a more rapid onset of muscular fat igue in the isolated muscle (dia- phragm) in contrast to the rats on a v i tamin depr ived diet. After admin is t ra t ion of glucose (1 g) per os, we noted no increase of the H.P . and R.Q. , cont rary to what is observed in the control rats and in the rats on an aneur in-depr ived diet (3-4 weeks2). F rom these re- sults we concluded that the av i taminos is Bj produced in a short t ime by the act ion of ant iv i tamin B 1 (N.P.) was more marked than that which is obta ined after 3-4 weeks of an aneur in -depr ived diet. Part icu lar ly inter- est ing to us was the lack of a change in the H.P. and R.Q. after the admin is t rat ion of glucose and, since the observat ion was based on only two exper iments due to the small quant i ty of N.P. at our disposal, we thought it proper to repeat it, as soon as we received a further quant i ty of N.P., k indly put at our disposal by Merck House (New Yorka).

    On other 3 groups (2 animals in each group; white rats, 75-85 g) t reated wi th endoper i toneal in ject ion of N.P. (5 mg pro die for 5-6 days consecutively) , we con- f i rmed what we had previously observed that after in- t roduct ion of glucose the R.Q. and especial ly the H.P . remain pract ical ly unchanged, which shows the lack of ut i l izat ion of the glucides, under the act ion of the ant iv i tamin. The R.Q. and H.P . were determined on groups of two animals each kept under a glass bell of known capaci ty for 10". The samples of air were analyzed with the Ha ldane-Margar ia apparatus . The glucose (1 g in 1 ml of water) was admin is tered by sound. The determinat ions were made after 40-60 rain. The results are shown in Table I. The fact that the non-ut i l izat ion of the glucides is due ent i re ly or in par t to an a l tered mechan ism of intest inal absorpt ion was not taken into considerat ion in the present researches.

    To expla in the di f ferent behav iour obta ined with N.P., we thought it exped ient to determine the contents of the tota l aneur in in the t issues ( th iochrome method 4 with adsorpt ion on Decalso and elut ion with acid KC1), con- s idering it to be a reasonable supposi t ion that the grav i ty of the av i taminos is must be preceded to an equal extent by loss of v i tamin in the tissues.

    We have taken into considerat ion (as shown by SEA- LOCK and WHITE 5 an interference of the th iochrome

    1 L. DE CARO and G. RINDI, Boll. Soc. ital. Biol. sperim. 28, 1869 (1952).

    2 L. DE CARO, C. CASELLA, and G. RINDI, Exper. 8, 431 (1952). s We particularly thank Dr. K. FOLKERS for his kind and frequent

    offers of samples of Neopyrithiamine. a Association of Vitamine Chemists, Inc., Methods of Vitamin

    Assay, 2nd Ed. (Interscience Publishers, New York, 1951), p. 111. 5 R.R. SEALOCK and H. S.WHxTE, J. Biol. Chem. 181, 393 (1949)

  • [15. III. 1954] Kurze Mitteilungen - Brief Reports

    Table I

    141

    Rats

    Neopyrithiamine* Neopyrithiamine* Neopyrithiamine Neopyrithiami ne .

    , Neopyrithiamine . . . . . . . . .

    f Avitaminosis** Controls**

    H.P. (Cal/m2/h)

    Before

    58"7 44-2 50-2 48-6 54-6

    51-2 2-5 58.1 :k 2-2 69.8 ::t: 1-9

    After glucose administration

    48.5 42.4 49.9 46.4 49-8

    47-5 1.3 67-2 jz 1.9 75.1 i 1-2

    Before

    0.73 0.64 0.67 0.84 {)-75

    0.72 ~ 0-03 0.78 :[: 0.007 0.81 ! 0.01

    R. Q.

    After glucose administration

    0-72 0.65 0-84 0.76 0-91

    0-77 -1- 0-045 0-92 :k 0-006 0.93 0-005

    * L.o~CARoandG. RiNm, Boll, Soc. itat. Biol, sperim. 2,% lS69 (1952). ** I.. m,: CAR{l, C. CASELLA, and G. RINm, Exper. 8,431 (1952).

    method with N.P., and in an effort to diminish this interference, we have reduced the oxidat ion t ime to the min imum (35 s) by col lateral tests of determinat ion of aneurin in the presence of various quant i t ies of N.P. The results are shown in Table I I together with the blood pyruvate values (Lu method, modif ied by FORNAROLP).

    Compar ing the level of aneur in of the t issues in animals t reated with N.P. with those of depr ived animals on an av i taminic diet of several days durat ion, it is observed that : in muscle N.P. lowers the aneur in contents to a level corresponding to a 5-10 day av i taminos is ; in the l iver the contents is lowered to a level equal to a 10-day avi taminosis ; in the brain N.P. lowers the contents of aneur in to a conspicuous degree, br inging the level to approx imate ly one hal f of that which is observed after 3 weeks of av i taminosis . N .P . shows, therefore, a part ic- ular specif ic ity in lowering the aneur in contents of nerv- ous t issue (brain), which, as is known, and as our results conf irm, is the most res is tant in respect to aneurin loss dur ing av i taminos is on a diet complete ly lacking in v i tamin B 1. The lack of ut i l izat ion of the glucides in av i taminos is B 1 seems to be in relat ion to a low level of aneurin present in nervous tissue, a level that is very seldom obta ined with a def ic ient diet, but which is obta ined rapidly with the admin is t rat ion of N.P.

    1 p. FORNAROLI, Boll. Soc, ital. Biol, sperim. 15, .511 (1940).

    In conclusion :

    Rats t reated with Neopyr i th iamine (N.P.), in com- parison to av i taminot ic rats result ing from a diet lacking in aneurin, and the controls, do not show an increase in R.Q. and H.P. after glucose admin is t rat ion .

    N.P. shows a part icu lar speci f ic i ty in lowering the aneurin contents of nervous t issue (brain), lowering it approx imate ly to one half of the level obta ined after 23 days of av i taminos is (diet).

    The lack of uti l ization of glucides, as is shown by the absence of a metabol ic response after glucose ad- ministrat ion, seems to be in relat ion to a low level of aneurin in the nervous tissue,

    L. DE CARO, G. RINDI, and E. GRANA

    Institute o/ Human Physiology, University o/ Pavia, September 23, 1953.

    Riassunto

    Ratt i t ra t ta t i con neopi r i t iamina presentano un con- tenuto part ico larmente basso di aneur ina nel tessuto nervoso (cervello) e non r ispondono alla sommin is t ra - zione di glucoso (per os) con aumento di Q.R. e di produzione calorica come, invece, fanno i control l i e i ratt i carenzati mediante la dieta (3-4 sett imane).

    Table II

    Rats

    Vitamin B 1 deprived diet days 0 days 5 days 10 days 15 days 18 days 23

    Neopyrithiamine 6 mg 5 days 6 mg 5 days 6 mg 6 days 6 mg 6 days 6 mg 6 days 6 mg 6 days

    Blood pyruvic acid rag/tO0 g

    1.35 ~ 0.07 1-77 i 0.06 1-42 ~ 0-11 2-16 i 0.37 2-37 :t- 0-26 2-94 t 0-42

    3.54 1-28 2.27 2-t2 1.93 1.96

    2-18 ~ 0.30

    Aneurin content (total) in the tissue Jtg,/g

    Liver

    7"42 =k 0-15 2"82 ~ 0"23 1-31 =}= 0-21 0-91 2}2 0-10 0-57 j= 0-05 0-71 :L 0.09

    2.08 1.44 1.19 1.20 1 "05 1.02 1.33 0-16

    Muscle

    1-60 0-05 0"80 ~ 0'(}7 0"52 ~: 0"06 O'34 ={: 0"03 0.40 :]:: 0.06 {)-31 :}= {).{)2

    l 11.75 0.65 I)-54 0.8l 0.75 0.79

    Brain

    3.38 0-07 2-89 -L 0-14 2-07 i 0-12 t-37 ~- 0-10 1-37 i 0.16 1-18 =}z 0.10

    0.71 ~ 0.04

    0-67 t}.55 0-57 0"53 0.57 0"58

    0"57 0.02

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