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Sugar u tilisatio n of the hearts of norm al and thyroidectom ised cats after adm inistration of

B ioch em istry

VI. Sugar u tilisatio n of the hearts of norm al and thyroidectom ised cats after adm inistration of

thyroxine. G. A m b ru s (Biochem. Z., 1929, 205, 194—213; cf. preceding abstract).—The sugar utilis­

ation of surviving hearts of thyroidectomised cats is considerably smaller th an that, of the hearts of normal animals, the decrease being the greater the sooner the experiment is carried out after extirpation. The hearts of normal and of thyroidectomised cats to which thyroxine has previously been administered use more sugar th an the hearts of corresponding animals not receiving such treatm ent.

P. W. Cl u t t e r b u c k. Influence of food on regulation of blood-sugar.

E. Ge ig e r and H . Kr o p e (Arch. exp. Path. Pharm., 1929,139, 290—301).—The sugar tolerance of rabbits as shown by the blood-sugar curves obtained after giving dextrose by m outh is increased by feeding on oats or adm inistration of alkali, b u t is decreased after feeding on green food or administration of acid.

These results render doubtful the validity of the method of Staub (Z. klin. Med., 1922, 93, 123; 1926, 104, 587) for ascertaining the efficiency of the insulin apparatus in the hum an subject.

W . 0 . Kerm ack. U tilisation of pentoses in the anim al organism . P. Thomas, A. Gr a d in e s c u, and (Ml l e.) R. Imas

(Compt. rend., 1929, 188, 664—666).—The propor­

tions of glycogen fixed in the liver and muscles of the male frog after ingestion of 4% solutions of certain pentoses have been determined by Pfiüger’s method.

Assuming 1 mol. of pentose provides 1 mol. of lactic acid, which is subsequently transformed into glycogen, then the maximum possible yield of glycogen is 54%.

Actually 51-24% of glycogen was formed from xylose and 54-90% from arabinose. J . Gr a n t.

Hepatic glycogen form ation from d - and J-lactic acid. C. F. Co r i and G. T. Cori (J. Biol.

Chem., 1929, 81, 389—403).-—'The glycogen content of the liver of 24-hr. fasting rats shows marked

increase after oral or subcutaneous administration of sodium ¿-lactate, a less pronounced effect after sodium r-lactate, and no change after sodium H actate ; this confirms the récent suggestion (A., 1928, 1286) th a t adrenaline stimulates the transform ation of muscle-glycogen into liver-glycogen through the stage of lactic acid. C. R. Ha r in g t o n.

M uscle-glycogen in m am m als. M. E. McKay

(Trans. Roy. Soc. Canada, 1928, [iii], 22, V, 329—

333).—The fall in glycogen content of the sartorius, gracilis, and gastrocnemius muscles of the rabbit and dog has been studied. W ith tho intact muscle this fall is not rapid ; it is greatest in tho sartorius and least in the gastrocnemius. Decapitate and decerebrate cats and cats the spinal cord of which was severed between the seventh cervical and first dorsal vertebræ were stimulated for periods of 1—30 min.

There was little evidence of the restoration of glycogen to the muscles following a period for recovery of 1 or

2 hr s. F. C. Ha p p o l d.

R em oval of glycogen from livin g m uscle. V.

J . M. H e r s i i e y and M. D. O r r (Trans. Roy. Soc.

Canada, 1928, [iii], 22, V, 151—157).—The effect of starvation, starvation and muscular exercise, severe exercise accompanied by cold, severe exercise and induced prolonged shivering on the liver- and muscle- glycogen of rats has been studied. None of these processes removed all tho glycogen. There is a more thorough removal of glycogen when strychnine is injected due to tho combined muscular convulsions and respiratory embarrassment ; the removal is not, however, complete. F. C. H a p p o ld .

H æ m opoietic action of bilirubin and other haemoglobin derivatives. F. V e r z I r and A. Z ih (Biochem. Z., 1929, 205, 388—401).—Bilirubin and hemibilirubin, and also hæmoglobin and hæmatin (which give rise to bilirubin in the body), fed to rabbits have a hæmopoietic action, but biliverdin has a much weaker action. Lower degradation pro­

ducts of bilirubin, as the porphyrins and bilirubinic acid, are without action. Bilirubin in largo doses has a liæmolytie action in common with hæmopoietic extracts of spleen and bone-marrow and with bile.

Bilirubin is active even after removal of the spleen.

I t is suggested th a t tho bilirubin and related products arising from the decomposition of the blood act as physiological stimulants for tho formation of red blood-corpuscles. J . H . B ir k in s h a w .

H æ m opoietic action of various organs. A.

Zih (Biochem. Z., 1929, 205, 402—408).—Bone- marrow, spleen, and lymph glands fed to rabbits have a variable hæmopoietic or hæmolytie action in con­

tra s t to lung and muscle, which are inactive. All hæmopoietically active organs belong to the reticulo­

endothelial apparatus and breakdown products of hæmoglobin may be present in the extracts.

J . H . Bir k in s h a w. P harm acological sy n ergism of stereoiso- m erides. D. I. M a c h t (Proe. N at. Acad. Sei., 1929, 15, 63—70).—Synergism is the term applied to the phenomenon exhibited by two or more drugs in which the pharmacodynamic effect of the m ixture is not a simple summation of the effects of the com­

468 B R IT ISH CH EJH C .iL ABSTRACTS.----A.

ponents. A study was made of the effects of a number of stereoisomerides on certain animals and plants. Timed observations showed in general th a t the toxic and pharmacological effects of the d-, 1-, and racemic forms varied considerably, and th a t a (¿¿-mixture exhibited a definite synergism.

N. M; Bligh. P hysiological action of derivatives of salicylic acid. I. K. K ase. II. K. Ease and K. Sek i

(Biochem. Z., 1929, 20 5 , 21—26, 27—30).—I. The methyl esters and the amides of o- and ^-hydroxy- benzoic acids are more toxic th an the corresponding free acids and their action resembles more closely th a t of the corresponding phenols.

II. The non-poisonous character of the hydroxy- benzoic acids depends on the presence of a free carboxyl group. P. W. Clutterstick.

T oxic effects of am ines. A. It. Johnston (J.

Infect. Dis., 1928, 42, 473—484).—The toxic effects of pyridine, quinoline, fuchsin, y-plienylenediamine, and amines generally are described. No relationship exists between the number of amino-groups in the molecule and its toxicity. Chemical Abstracts.

Effects of derivatives of betaineam ide and of choline ethers on the autonom ic nervous system . R. Hunt and R. R. Renshaw (J. Pharm. Exp.

Ther., 1929, 35, 99—128).—The effect on the blood pressure of the anassthetised or decerebrated cat of a large number of derivatives of betaine of the general formula NMe3X-CO'NHR, (R = an aliphatic or aromatic radical and X=C1 or Br) as well as of several derivatives of choline and homocholine, has been studied. The muscarine-like action and the nicotine stimulating action are influenced by the substituents, the phenyl group in particular decreasing the muscar­

ine action and increasing the nicotine stimulating

action. W. 0 . Iyermack.

Action of choline on gaseous m etabolism . H.

Tangl (Arch. exp. Path. Pharm., 1929, 1 3 9 , 220—

225).—Subcutaneous injection of choline into fasting rats increases the metabolism, the maximum effect occurring 2—6 hrs. after administration.

W. 0 . Kermack. Guanidine structure and hypoglycsemia. P.

Bischoff, M. Sahyun, and M. L. Long (J. Biol.

Chem., 1929, 81, 325—349).—A number of guanidine derivatives have been studied with respect to their hypoglycemic activity and their toxic effect on the liver and kidney, the latter being measured by changes in the carbamide- and amino-acid-nitrogen of the blood. In the aliphatic and alicyclic series, the toxicity towards the lddney appears to be char­

acteristic of the guanidine group, whilst hepatic injury is produced by those derivatives which cause hypoglycemia, and in a parallel degree. Aliphatic guanidine derivatives containing cyano-, carbonyl, carboxyl, or hydroxyl groups are devoid of toxicity and of hypoglycemic activity; acvlation reduces the toxicity of guanidine. Aromatic guanidine deriv­

atives exercise a toxic effect distinct from th a t of the aliphatic compounds; some of them have also a hypoglycemic action. The diguanidinopolymethyl enes (homologues of synthalin) show a higher degree of hypoglycemic activity th an other derivatives, the

activity increasing with the length of the carbon chain. Of th e compounds studied so far,, guanyl- piperidine is unique in showing a definitely greater hypoglycemic than toxic action, and in producing a rapid hypoglycemia (preceding depletion of the glycogen stores) in which respect its action simulates th a t of insulin. C. R. Harington.

Substances producing hypoglycsem ia. I.

Syntheses of guanidine derivatives. T. Kumagai, S. Kawai, Y. Shikinami, and T. Hosono (Sci.

Papers Inst. Phys. Chem. Res. Tokyo, 1929, 9, 271—

275).—Hexamethylenediguanidine, octainethylenedi- guanidine, and decamethylenediguanidine (“ synth­

alin ” ) are approximately equally effective in pro­

ducing hypoglycemia in rabbits. Octamethylene- diguanidine is slightly more active th an the other two compounds. The following compounds are described, the guanidine derivatives being produced by the condensation of iS-methyl-^-thiocarbamide

■with the appropriate am ine; (3-3- indolylethylguan-idine hydriodide, m. p. 141—142°; pentamethylene- diguanidine sulphate, decomp. 330°; hexamethylene­

diguanidine hydrochloride, m. p. 179—180°; dibenzoyl- octamethylenediamine, m. p. 169-5°; octamethylene- diamine hydrochloride, m. p. 284° (decomp.); octa- methylenediguanidine hydrochloride, m. p. 176-5:

decamethylenediamine hydrochloride, m. p. 309—310°, and decamethylenediguanidine hydrochloride, m. p.

193°. W. O. Kermack.

D istribution of quinine in the blood. 0 . S.

Gibbs (Proc. Nova Scotian Inst. Sci., 1928, 17, 114—115).—Blood containing quinine was separated by centrifuging into a serum layer and a blood-cell layer. The quinine was found to be equally dis­

tributed between the two layers. When the blood is haomolysed before being centrifuged, the lower layer, containing the “ ghosts ” of cells, has 6—40%

more quinine, owing probably to adsorption on the cells. A modification of Ramsden and Lapkin’s method for the determination of quinine gave unsatis­

factory results (cf. King and Acton, A., 1921, i, 474).

B. W. Anderson. A ction of vapours of ethyl and m ethyl alcohols, ether, and chloroform, and of illum inatin g gas on leucocytes. (Signa.) C. Forti (Atti R . Accad.

Lincei, 1928, [vi], 8, 700—705).—The amoeboid activity of the leucocytes of toad’s blood is paralysed in a few minutes by the vapour emitted by small quantities of ethyl or methyl alcohol, ether, or chloro­

form. Illuminating gas (40—50% of carbon mon­

oxide) produces first increased, and later gradually d iminishing movement of the leucocytes, complete arrest setting in only after 8 or 9 hrs. According to the duration of the action, these effects m ay be either permanent or transitory. T. H. Pope.

Com bined narcosis. I. E ther and chloro­

form . II. N itrous oxide and ether. III.

A cetylene and ether. L. Lendle (Arch. exp. Path.

Pharm ., 1929, 1 3 9 , 179—200, 201—210, 211—219).

—I. When white mice are anaesthetised by mixtures of chloroform and ether the speed of narcotisation increases, whilst, relatively to the dose necessary for light narcosis, the narcotic range (cf. A., 192S, 920) decreases, as the proportion of ether in the mixture

BIOCHEM ISTRY. 469 is increased. The secondary toxic action of the

anaesthetic also decreases with increase in the pro­

portion of ether.

II. W ith mixtures of nitrous oxide and other the anaesthetic action is not additive, but with addition of nitrous oxide to tho m ixture the total anaesthetic effcct tends to decrease. Tho narcotic ranges of the mixtures investigated were approximately tho same as th a t of pure ether.

III. Tho relative narcotic range of mixtures of acetylene and ether is approximately independent of the proportion of the two anaesthetics. The ancesthetic effect of such mixtures is an additive function of the constituents. W. 0 . Kermacic.

Relative physiological properties of certain 5 : 5-dialkyl- and l-ai-yl-5 : 5-dialkylbarbituric acids. A. M. Hjort and A. W. Dox (J. P h a rm . Exp. Ther., 1929, 35, 155—464).—The anaesthetic action on mice has been studied. In the case of 5 : 5-dicthylbarbituric acid the introduction of a 1-aryl group does not improve hypnotic properties, but in tho cases of 5-etliyl-5-?i-propyl- 5-ethyl-5-?i- butyl-, 5-e th y 1-5-isobutyl-, and 5-ethyl-5-JSoam yl- barbituric acids, the presence of a 1 - aryl group decreases the toxicity of the compound and hence improves it as a hypnotic. Neither 1 : 3-diphcnyl-5-ethyl- barbituric acid nor the p-ethoxyphenjimonoureide

•of ethyl-H-butylnialonic acid has anaesthetic action.

The following barbituric acids have been prepared : l-~p-tolyl-5 : 5-diethyl-, m. p. 152—153°; 1-p-anisyl-5 : 1-p-anisyl-5-diethyl-, m. p. 126—127°;

I--p-cthozyphenyl-•5 : 5-diethyl-, m. p. 152— 153°; l-j)-chlorophenyl-5 : l-j)-chlorophenyl-5-diethyl-, m. p. 135—136° ; l-p-bromophenyl-5 : 5-diethyl-, m . p. 186°; l-phenyl-5-ethyl-5-j)ropyl-, m. p. 152—153°; l-phenyl-5-ethyl-5-\&obutyl-, m. p.

149°; l-phenyl-5-ethyl-5-n-bulyl-, gummy ; l-phenyl-5- ethyl-5-isoamyl-, m. p. 130°; 1 :3 -diphenyl-5-ethyl-, m. p. 145°; also th e 'p-ethoxyphenyhnonoureide of ethyl-n-bulylmalonic acid, m. p. 124—125°.

W. 0 . Kerm a ck.

“ N octal ” and “ pernocton .” III. B ehaviour in the organism . TV. D eterm ination of the activity of sim ila r barbituric acids. V.

Influence of the structure of the alkyl group on th e activity. F . B o e d e c k e r and H. L u d w ig (Arch. exp. Path. Pharm., 1929,139, 353—356, 357—

360, 361—372).—I II . 5-woPropyl-5-acctony]barbit­

uric acid and o-tsopropyl-5-carboxymethj'lbarbituric acid, into which “ noctal ” (5-i'sopropyl-5-P-bronioallyl- barbituric acid) is presumably converted in the animal organism, are without toxic action. The corresponding sec.-butyl compounds derived from

pernocton ” (5-sec.-butyl-5-(3-bromoallylbarbituric acid) are likewise inactive.

IV. The following compounds are all strong hypnotics : 5-isopropyl-5-y-bromoallyl-, 5-i'sopropvl-5-p-chloroallyl-, 5-{sopropyl-5-[3y-dibromoallyl-, 5-di- (p-bromoallyl)-, and 5 : 5-di(chloroallyl)-barbituric acids.

V. Of the following barbituric acids : 5-a-methyl- butyl-5-allyl-( o-a-methylbutyl-P-bromoallyl-, 5-sec.- butyl-5-allyl-, 5-sec.-butyl-5-|3-chloroallyl-, 5-a-phenyl- propyl-5-allyl-, 5-isopropyl-5-|3-bronioallyl-, 5-iso- propyl-5-fi-chloroallyl-,

5-a-ethylpropyl-5-p-bromo-allyl-, and 5-dimcth}ipropyl-5-3-bronio5-a-ethylpropyl-5-p-bromo-allyl-, those containing an asymmetric carbon atom are par­

ticularly potent hypnotics. The physiological and pharmacological actions of “ pernocton ” have been investigated. W . 0 . Iverm ack.

“ A v e rtin .” A. We l sc h (Arch. exp. P ath.

Pharm., 1929, 139, 302—312).—After adm inistration of “ avertin ” tho bromine of tho compound is quantitatively excroted in tlie urine within 48 hrs.

The urine gives Arnold’s reaction (with sodium nitro- prussidc and alkali) much more markedly th an does normal urine and it contains a substance which inhibits tho reduction of Fehling’s solution. From the urine after precipitation with lead acetate a barium salt was obtained which was apparently an impure m ixture of the barium salts of cystine and of

“ avertin ’’-glycuronic acid from which this latter acid was isolated. W . 0 . K e rm a c k .

U se of m agn esiu m as an aid in a n esth esia . I. N e u w i r t i i and G. B. W a l l a c e (J. Pharm. Exp.

Ther., 1929, 35, 171— 187).—Administration of m ag­

nesium sulphate or lactate to dogs by mouth or per rectum does not raise the magnesium content of the serum to the level a t which analgesic action is pro­

duced, viz., 5 mg. per 100 c.c. This level is reached by the administration subcutaneously of 0-25 g. of magnesium sulphate per kg. body-weight. Profound anaesthesia occurs when the serum-magnesiuni is 20 mg- or more per 100 c.c. I t is considered unlikely th a t magnesium salts aro of use in colonic anaesthesia mixtures or in obstetrical analgesia -when employed in the usual doses. W . 0 . K e rm a c k .

Action of large am ounts of iron. II. Action on blood, grow th, fertility, and lactation. K.

W a l t x e r (Biochem. Z., 1929, 205, 467—472; cf.‘

ibid., 1927, 188, 38).—R ats receiving an addition of 2% of reduced iron to a complete diet show7 no change in the blood, b u t with a rachitic diet anaemia develops. The iron also delays growth a t the age susceptible to rickets. The lessened fertility and secretion of milk produced by the reduced iron are cured by vitamin-/). J . H. B ir k in s h a w .

[Physiological] action of sulphur. L . Pisr- c u s s e n and E . G o r n i t z k a j a (Z. klin. Med., 1928, 108, 369—377; Chem. Zentr., 1928, ii, 1347).—

After application of sulphur the blood-sugar, -diastase, and -catalase are unchanged, but the tributyrin esterase is diminished. A. A. E l d r i d g e .

T oxicology of bism uth. II. D istribution in the organism after injection of aqueous solutions of b ism u th com pounds. R . Fab Re and M. P ic o n (J. Pharm. Chim., 1928, [viii], 9, 97—112; cf. A., 192S, 12S0).—A stu d y of th e distribution of bismuth in th e tissues after intravenous injections of aqueous solutions of bism uth cacodylate, “ bism uth campho- carbonate,” and am m oniacal bism uth citrate.

B. A. Ea g l e s. Excretion of b ism uth from the hum an organ­

ism . W . E n g e l h a r d t (Arch. Dermat. Syphilis, 1928, 156, 1—42; Chem. Zentr., 192S, ii, 1461).—

Considerable quantities of bismuth are excreted in the faeces and urine during treatm ent of syphilis by bismuth preparations. Up to 50% is so excreted,

470 B R IT ISH CHEMICAL ABSTRACTS.— A.

most rapid excretion taking place after intravenous injection. Oil suspensions are irregularly excreted.

A. A. El d r id g e. Electrolytic determ ination of lead in urine. T.

C o o k se y and S. G. W a l t o n (Analyst, 1929, 54, 97—99).—The urine is made acid with acetio acid and lead deposited elecfcrolytically. The deposit is dissolved in nitric acid and converted into chloride, and lead is determined by comparing the turbidity resulting on addition of a solution of potassium metabisulphite against a standard. The lead con­

tent of normal urine varies between 0-02 and 0-05 m g./litre; mean, 0-04. J . S. C a r t e r .

R esistance of the nem atode, A n g u illu la aceti, Ehrenberg, to various protoplasm ic poisons.

J. B e le h r .4 d e k and V. N e o I s o v a (Bull. Soc. Chim.

biol., 1929, 1 1 , 65—69; cf. A., 1928, 1279).—

Anguillula aceti resists the action of 2-5% aluminium chloride and 2% barium chloride solutions for consider­

able periods. The times of survival to potassium cyanide, mercuric chloride, and cupric chloride are greater than those of Cypris and Tubifex. The resist­

ance is probably connected with the constitution of the epidermal tissue. G. A. C. Gotjgh.

Strontium thioacetate as an antidote in poisoning by m ercuric chloride. C. C. H a s k e l l and J . C. F o r b e s (J. Pharm. Exp. Ther., 1929, 35, 147—153).—Dogs poisoned by mercuric chloride administered either orally or intravenously were apparently not benefited by the administration of strontium thioacetate. W. 0 . K e rm a c k .

Effect of X-rays on the process of enzym e form ation in the isolated pancreas. A. I.

B o g a y e v s k i and B. G o l d s t e i n (Zhur. exp. Biol.

Med., 1928, 9 , 328—334).—Stimulation of the gland cells by the action of X-rays on the perfused pancreas yields a fluid containing a greater concentration of amylase and lipase. A n excessive dose diminishes the activity. C h e m ic a l A b s t r a c t s .

Absolute absorption spectrum of the resp ir­

atory enzym e. Photochem ical dissociation of iron pentacarbonyl. 0 . W a r b u r g and E. N e g e - l e i n (Biochem. Z ., 1929, 2 0 4 , 495—499).—Certain results communicated in former papers (cf. A., 1928, 549, 851, 1390; this vol., 216) require to be multiplied by the factor 2-2. The photochemical dissociation of iron pentacarbonyl has been reinvestigated and it has been found th a t one molecule of carbon monoxide per quantum of light is split off. W. M c C a r tn e y .

Cytochrome and respiratory enzym es. D.

K e i l i n (Proc. Roy. Soc., 1929, B , 1 0 4 , 206—252).

—Yeast cells contain a powerful indophenol-oxidase system which is easily revealed by the oxidation of p-phenylenediamino. The oxidase is thermolabile, being irreversibly destroyed .by boiling or heating to 70°, is strongly inhibited by potassium cyanide and hydrogen sulphide but not by sodium pyro­

phosphate. This oxidase system is inhibited by the reducing systems of the cells and so is active only in presence of various narcotics such as urethane or after the cells have been warmed for 1A hrs. a t 52°

or cooled to —2°. Dried yeast and zymin give only feeble reactions. The oxidase system is inhibited

by carbon monoxide, which appears to form an inactive compound with it. This compound is, how­

ever, readily destroyed by oxygen and by light.

Quantitative measurements by means of a Barcroft manometer demonstrate th a t the amount of carbon monoxide combined with the yeast oxidase is pro­

portional to the partial pressure of the carbon mon­

oxide and th a t th e oxidase molecule has much greater affinity for oxygen than for carbon monoxide. The oxidase activity of yeast-cells and the total respiratory activity are with a few exceptions similarly affected by reagents. An oxidase system with properties similar to b u t not identical with th a t found hi yeast is present in a preparation of washed heart-muscle.

The properties of polyphenol-oxidase from potato have also been investigated. This enzyme can be obtained as a clear solution unlike the former two, which it has not so far been possible to separate from cellular material. I t is considered th a t the indophenol-oxidase plays an im portant rôle in cell metabolism. The properties of the components of living cells which are derivatives of hœmatin are described. Cytochrome is composed of three hæmatin compounds, a1, b1, and c1, and an unbound hæmatin compound similar to the protohæmàtin of hem o­

globin, of which the components a1 and c1 are not, whilst the other two are autoxidisable. I t appears th a t the factors, e.g., potassium cyanide, propionitrile, hydrogen sulphide, carbon monoxide, drying the cells, treating them with alcohol or acetone, which inhibit the activity of indophenol also inhibit the oxidation of cytochrome, whilst the. factors, e.g., narcotics or warming to 52°, which have little effect on the activity of indophenol-oxidase do not inhibit the oxidation of cytochrome. I t is concluded th a t cytochrome is oxidised by the indophenol-oxidase. Cytochrome in the living cell is reduced in presence of dehydrases by the hydrogen donators present, which are themselves oxidised. Cytochrome is thus considered to act as an oxygen carrier in the oxidation of the cell metabol­

ites, being alternately oxidised through the action of the oxidase and reduced through the action of the dehydrase. Some other possible functions of in tra ­ cellular hœmatin compounds are discussed as well as the nature of the oxidase. W. O. Ke rm a ck.

D extrose-oxidase. II. D. M ü l l e r (Biochem.

Z., 1929, 2 0 5 , 111—143).—In the press juice and hi the alcohol, alcohol-ether, and acetone precipitates of the press juice of Aspergillus niger an enzyme is

Z., 1929, 2 0 5 , 111—143).—In the press juice and hi the alcohol, alcohol-ether, and acetone precipitates of the press juice of Aspergillus niger an enzyme is