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It is perfecti certain that Manquat, in his excellent Traite elemen latre de Therapeutique ' hicli Phave before me, says: It is selessio discus at an lensi the mode of actio os quinin in malaria . But on the other hansit is noctes certain that is his siste colleaque and compatrio Cl. Bernard professor of the Colles of France had thouulit the fame thing, should notino anythininabout the actionos curare an possibi me hould e naware of the physiolossicalfunctio of the nerve motor-ptates. Nor et is other investigatorshad follo e the opinioni Manquat, ould atropin e sed formahin clea the lesion of the pneumosastri nerve and it,ould nothave been possibi tomahe se of clinica examinatio of these and other elements hic have so much contribute to clinica develop-
II. Ouinin is an almos inexhaustibi Source of radio-activit9. As follows hom the experiment cite it is possibie, meret bydehydratin and hydratin the sulphate os quinine, constanti toobtain light an radio-activity A the experiment canae repentedan infinite number of timescit follows that with a limite quantit ofquinin there canae obtained a practicali inexhaustibi quantit ofradio-activity. The quinin is not exhausted however much the experimentie repented. Quinine likewis undersoes no chemicat alterationi in to containing more or ess water of crystallisation. The crystals of quinine seen by me unde the microscope before an after the experiment ho no appreciable variation. it chemica reasent the reactio isentiretnidentical It is like the platinum ire hicli, without alterinsit chemica composition acquires entiret ne properties o the passage of the electri current. The experiments et out beto aredirecte to the objecti illustratins his vie .Hoi the fame cause can produce opposite effecis.when the quinine loses ater, o in to heat, the dry at o the dehydratin agent et . it shines in the darkness,ith a freenis lishi:
out in consequence of the absorption o water, but light up asainwhen theireat stops This operationi pultins ut the phosphor- escence due o desiccationis the quinine by breathins may be repeat
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O the ther and is, wai unti this first phosphorescence of dehydration is extinguished and after havin taken the quinin awayfrom thetare the actio of heat o the dryin rensent, it is again breathedin the phosphorescence hic inas preolouSI seivin out, Iight up again o in t action of the moisture of the breath. It is thephosphores ence of hydration hic coincides illi the diffusionis radio-activitY Thus there is the extraordinar case of a light oinsout with one breath and lislitin up again by another. This phenomenon is characteristic of the sulphat o quinine. It is like is presented though,ith much les enersy by sulphat oscinchonine This differenc sussice to distinguis them. In orde to explain his fac it ould by necessar to modisystishtly the theor of matter and energy It musti supposed that Some ne force is released and that this is due to the dissociationifthe atom os quinine, ther ise, should have to admit the absurdit that with a limite quantityis matter, an indefinite quantit ofener cis obtained.
The author now describes how the phosphorescen eris a simple means os detect- in quinin in aso der, and further some experimenta hic prove that quinine moue actino chemi Ity diminishes the sensibilit for tish of silver salis.
The actionisquinine recalis that of the antiaoxidases. From the foresoin experiment it is seen that quinin retard theoxidationis salts of silve by light in the fame a ascit retardsthe xidationis tincture of suayacum by the protoplasm of the potatomino, extinguishes the phosphorescence of the schizomycetes and prevent oxidatio of the erythro tes. These last three experiments were explained by sayins that quinine, promplaSmic polaon operate by reducin the vitalit of the protoplasm, and consequently iis capacit of oxidation. In his caselikewise, the quinin acts by preventins Oxidation, but the protoplasm es no exist, and consequently the quinine cannot have acted a apoisoni reducin an vitali . Consequently it musti inferred that quinin has no acte chemicali butis virtve of a physico-chemicat action By this true actiono presence, hic recalis the actio of the anti-oxidASeS, quinine ould operate by delaying the oxidationis ali the protoplasms, and in his an ould reduce the vitalit of the celis o whicli it acta, b producin true cellula asphyxia Thus it actioni the celi ap
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I this ere no the case it,ould noti possibi to explain halis the actionis a substance hic passe through the organism exercisin an undoubte curative action, accompanie by ver varied alterations in physiological conditions and whicli is after ard eliminates ithout havins undersone an note orthy hemica alterations and in a quantit almos equa to that whic entered. Comparison Betieen the actionis radium and that os quin me. Continuin in the view of considerin quinin a a radio-ActiVemedicine or the fource of physico-chemicat energyd decidesto inve tisate the analogies of action belween radium, the modet of this classo medicamenis and quinine, the objecti the present modest study. The folio in is the result of the compBriSon. RADIUM
Destroys the celis, the nutritive mutntions of hic are mos rapid whose processis nuclear division is hortest: hic are richest in protoplaSm, ndwhic are cytogeniticali FoungeSt. The neoplastic celis are the rs todie unde it Rction. The phasocytes delanthei amiboid movemenis under large doses the exasserat them under mali ones. O large doses the glycogenie functionis the live diminishes. The volume of the spleen is reduced. Planta are more resistent thct Animala, the major par of the microbes resis ita actio meli. Localinit is causti and irritant. Untimet use or excessive doSe re duce the resistence of sound tiSSue.
Quintne has been used in inoperable cancer D vlau 900-1908ὶ Mormnit 893 advised the interstitia injectionos the cancer focus illi quinin in thetreaimenti canceri X rays. e sam is the case it quinine. In large doses it prevenis the glyco- senic functions of the live an in mallones it stimulates them. The SHme.
Quintne hic insit kill proto ais likewise less fata tota teria. Quinin is likewis in both cases. Whe wronsfully used it reduces theresistence of the re corpuscies haemo- globinurea, hematurea an ali the tis-
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It akes hemica ferment inactive
The radium salis mos in uSerare: Sul-phate, chloride andiromide. The radium salts are phosphoreScent.
It impresses phot rophic plates,ith
It is a chemicat disintegrator and op-POSes the reactions of Synthesis in large doses, hil in mali ones it stimulates
It improves exophthalmi sotire. Radio-activit and X rays have beenused successisti in malaria splenome- salin.
Quinin in large doses reduces theactioit of the lio protoplasm Poucheti. In mali doses it has for many
years been sedis atonicand Stimulant. Quinine also improvecit. Quinine reduces the siete of the spirenand cures the fame plenomesalict.
Pharmaco nam se of quinine. Letis follo quinin in iis progress through the organiSm. On reaching the stomach it is dissolved in consequence of the fastricacids Manquat'. The carboni acid of the intestina content must exercise a favourable actionis this proces Gaselio . In oin offac the quinin whicli precipitates in consequence of the carbonate of sodium, is no precipitate is there is adde a dilute solutio ofbicarbonate of sodium illi re carboni acid. The bile produces in quinin solutions a precipitate os insolubleslycocholate os quinine whichas decomposed by the carboni acid and by the aikaline carbonates. In the intestine here these acid do notexis the quinin is hardi absorbe at ali that is hycit is adlyabsorbe when administered by enema. Quinin alSo exerciSe ni ofold actionis the epithetium of the stomach and the intestines accordininto the dose. In mali doses it stimulates thei functio producins an increas of the digestive uices thus stimulatins the appetite an increasin the digestive functionS.with ars doses rhadly administereddoses it tannistes the mucous membranes of these orsans and the alterations of the absorptionstudie by Heidenhain an subsequently bHO. Cohnheim present themselves Promethese experiments it is deduced that with thepolsoned
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mucosae resulis are obtaine simila to thos produce in the eadanimal absorption dropSeto disappearance potnt even illi crystalloidsand the intestinat wal lose iis power sint allatino iraeUt Betraversed in ne specia directin These Xperiment Serve to provethat absorption has for it basis a livin and organised substance hic is alone capable of effectinscit. A Cohnheim Mund that the solution os fuga introduce into the polsoned intestinat loop. causes a considerable quantityis chlorideo sodium cominifrom the sanguineous and lymphati plexuses, thesam thins happens illi quinine, that suo say, after the administra tionis large doses ursin effect occur, beCctus the intestine seis fille mit sanguineous plasm in consequence of the annification
These mucous membranes in whic necrosis is produced by quinine, lose the properi os no allowin themselves to e diueste by the intestinat uices thenare attacked an corroded by them henc thesastrointestinaliain and the vomiting. hicli constitutem defensive sympto by hicli the sat orsan relieve themselves of the uices attachin them o in to this defensive mechanism there ill occurin the intestine anti-peristallic movemenis able o cause the bile toappea in the vomit. In his way an obstacle to the rus is created polsoning of the mucOSct, Suspensio of the absorption and defensive vomiting.
VThis protective functio has in particula forciis basis that capacit os physiola-ψica selection hicli, have found in the intestina epithetium, owin to hicli, while the absor independenti of the law of osmosis certain non-diffusibi Substances the domo allo themselves tot traversed by thers hichire more diffus-ible ' Luciarii).wit therapeuti doses these symptom domo usuali occurrandconSequently the quinin is easit absorbed. heins found in the feces Herner . ut it a b state that large doses capabiei altering the mucosae are notini no absorbe but they, is Anythins, reventili absorptioni allisther SubStanceS.when onc it has traversed the gastrointestinat epithetium, quinine mahes iis anto ard the live through the portat system. E. Cavazzani studying the glycogenie functionis the liver brinus oui the followins facts whichae copied rom Luciam physiolosy.
Methylene lue. hich does no alter the saccharilain actionis hemodiastaSiS, when injecte into the circulation fixemitself preferentiali in the live an in a suit- abi dos prevenis asphyxia hyperglycema andireatly reduces the post mortem GlycoseneSiS. Nevertheles methylene blue a vias Already known by earlier studies Andhas been confirme by E. Cauarzani possesses aratrons Aralysin Rctionis the
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Theclive stores ali classes of poisons whicli, arrivinci by the portalvein, are delaine by the hepati celis, hic accumulate them in acytoplasm deStroys them in part in part Send them to the intestinethrough the medium of the bile, an in pari finali dissipate themflowly throus the hepati Veins, so that the are aster ard eliminated by the renat emunctHry.
proved that the fata dose formarcotic OisonS, nicotine hyΟScinmine, is much es by hypodermi injectio than when injecte direct into the porta vein. This power of the live os destroyin or reducin the toxic actionos aikaloid does no occur in other orsans. Lucitano. Minera polsons may ascis ellanown be rendered harmies and accumulate in his gland whic fac Orsila was the firstri potnt oui. The compound of lead copper, arsenic iron. etc. accumulate in the hepati celi. The accumulationis ron in the liverris important, heinsa fac whichiussana connected wit the hematoseni and haemost binoseni action Diron medicamenis, hic mas confirmed. Mar*ri
l893ὶ in the laborator of Schmidebero, findins in the live a combination Diron it albumen similaro globin to hichae aveth nam offerretine. Heper 1873-77 effecte the artificia circulatio of the solated live wit defribinised and nicotinised blood, observins that on pBSS- in to the live the nicotinised blood ost it characteristic odour Bysubsequent investigations heriound that the live absorbs an retainsfrom 25 to 50 per cent of the aikaloid whicli passed throus it Strychnine, quinine, morphia and nicotine).
The solutionis quinin salis, Orphia, atropin curare, etc., injecte into the intestina vel of the rabbit, how a toxicit nearly one-hal les than when injected into the peripherat eius .
Theclive degeneraled by polsonins it phosphorus o renderedcirrhoti by ligatur of the choleduci is no longe able to exerciSean essective actio against polsons. The fame happens to the livero animais hicli, o in to the effectis polsonins have lost their glycosene. In the foeta development also the appearance of the protective actio of the live coincides it the accumulation offlycosen therein. Thus, se that this anti-toxic actionis the liverris directi depend-
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Schroede 6 Salomon, vallin themselves of artificia circulationthrous the live and chemicat analysis of the blood before an after circulatins through themaid orsan found that is carbonate os ammonia be adde to the loo it is transforme into urea, after havinspassed through the liver. his transformatio is due to a synthetic proces produce by the hepati celi, by hic the carbonate ofammonium by losin inater, is converte into urea. On passin theblood through the kidneysi muscies his transformatio doe not
Consequently we are justifed in assumin that quinin undersoes in the live a proces of dehydration and polymerisatio simila tothe foresolns Perhaps the glycogenes stycos Without water contributes by hydratin iiself. to this dehydration o quinine. For therest, his is no in the leas necessaryaecause the solutions of radio-
This radio-activit of hydrationi dissolution the forme proved experimentally. ould e theso er hic destroy the parasite osmalctria, reventin ita germinctiion. This must he assumed hecaus other is one fatis to understandhow his quinine, havin such varied andio eria influences o allthe celis of the organism, emerses unaltered with the greater par of the Secretions bile, ears, Saliva, milk, urine, etc. Ont in his atteris it found in a quantityis a third o more of the tota dos and ithas tost in pomer of crystallisatin amorphous inactive quinine ofGuotieni. thydroxilquinine of Kerneo. Actionis quin me on the element of the Blood. From the live the quinine passes sio ininto the blood circulationan gradualty impregnates the blood and tissues, producing the excit in effect in ali the celis of smal doses both as resard radio-actiVit an quinine. Aster ards to ard the fixi hour Manquat the degre os concentratio of the quinine ouldae at iis maximum and Dis then iis
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actio mahes itfel fellis the elements of the blood and the tissues. reducin thei vitalitY. t is thus seen that durins therars moments the leucocytes increas thei amiboida movement an after ards
radium reduces the number o leucocytes by V after acie hours minet, Scharrenbroth . Bina demonstrates paralysis of leucocytes in the mesentary of theseos by the actionis quinine, ut these experiment mere follo ed by ther of Hayem Bochefontaine Dusset re from hic thesewriter conclude that the movement of the phasocytes are notreduced. hut that in the ther hand they flee byaeasonis a phenomenonis negative chimio-tHXiS.It willi seen that at the bottom of this apparent contradictioniffacts there is ni a question DdoSeS. Assumin the radio-active emanation, it is seen that applyin thequinine to the mesentar of the fros, iis energnis ablerio stomandparalys the movements of the phasocyte is the lalter underuo iis clos and intense action, hile the migh likewiseae able to defendthemselves by fleein to the deeriparis heiare undersolns the actiono radio-actiVity. Subsequently the paralysins actionis large dosesin the leucocytes a demonstrate experimentali by incent in his studY Tetanos et quinine), in hic he proves that the subculaneous injectio ofquinine, o in to the inhibitatio of the phasocytes, promotes thegeneralisationis therapores of the bacillus of Nicolair, producin arapidi mortal tetanus, hic very much recalis the splanchnic tetanus o Binot. Accordin to Breguet, quinin increases the fibrine and reduces the
the organism prove that blood Oxidises the tincture of suayacuminaddin spirit os turpentine, hicli sive up Xysen and BSSume Bblue colour: his reaction does no occur in the presence of quinine.
My experiment With silver salis tenda prove that quinin retardsthe oxidation similarly to antioxidases by reason os a physico-chemiccti, or ather physica action. From these experiment it follows that
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quinine, in orde to reduce the oxidatio of the blood, oes no needio combine intimatet with haemoglobin, as was assumed by Bin and
The rapi eliminationis quinine, hicli appear in the urine tenminutes after iis administration Pirry, Lavaliae constitute another argument against this intimate fixture os quinin in haemoglobin. Actioni the muscular cella. O the muscula celis quinin acts in mali doses, increasin their capacit os contraction: in large doses it annuis his contractilily. Thus the heari is seen with smali doses stistitinio increas iis rhythm,
wit larue doses weakenins follo si a period of acceleration, with ossis eners an fallis the blood pressure ove a long period. I the dos is fata the hear stops in diastole. Thus it happenesin a casei Giacomini, cited by Manquat, heredeat occurre aster takin 124rams: another case of ille eici: this has also been confirme on animal by Laborde and Brestuet Although toxic doses are paralysin to the heares Lewitzky l869ὶ, this orsan is the las m dies Bochebontaine . Probabina direct actiono quinin o the hear is in question the increas of the number of beat does no appea to e due to a reductionis the tone of the VHGu nerve because the paralysis of the vasus is no observe untii after ver heau doses of quinine and then the paralysis is neither complete nor constant ' Gaselio. The muscula fibres of the esset contraci it smal doses of quinine, hicli fac Contributes, o increas o cardia activi , to increasing the pressure with large doses the said fibres are paralysedand the vesset expand reducin the preSSure. This paralytic vasodilatation explain the haemorrhase hichquinin is capable os producin in histit vascularise mucosae Forthis reason it is sed in mali doses in obstetrics whil in large doses it produces anserous haemorrhase, hic ma even occur in the interna ear. In the Sal orsan, o ins to this paralytic vasodilatation, by large doses of quinin there is ensendered a reater secretion fendolymph hic is capable os producin tinnitus an deafnes be- cause the increas of endolymphati pressure deranses the physicalcondition in hic the Relasne and the tectorium membrane function, and the physiolos of the semicircula ducis is also altered, producin quinin intoxication. The muscies increas their orkin strain, a there is like is adirect influence of the quinine n the contractile element hic iS
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observe even in fros treate mitti curare Falla Piccinini . The
uterus lSo increaSe it contractions durins labour, even independenti of the influence of the centres, hen the nerve Hre SeVered.
The spleen enlarsed by malaria and the normal spleen re reduce insigei quinine. In the do it is possibi to observe the contractio of the spleen unde the influence of quinine. It is no a questionis an action hich
tracte even after the sectio of the nerves distribute throus it Morier. an is, is the nerves are firSt ut thenis vasomotor paralysis the Spleen increnses in volume but nevertheles the quinine continues to contraci the Aid orsan. O the nervous celis it exercise an identica actionis stimulation in mali doses, whil on the other hand in large doses it destroys theirenersy, producin Annigesin. The cellular interchanseris stimulated by the radio-activit os quin-ine in mali doses and reduce in large doses. It antithermi actio is like is explained by the reductionis cellula activit an by iis actioni the malaria agent. Actioni me plasmodium. Quintne has an injurious actioni the ouns forms of the proto-Zoon, particulari in the extra-globula phase of life whicli follows complete sporulation Like is in the initia forms,hich have atready invade the re corpuscies, quinine eXercise it action, reventingtheir further development But when the stage of segmentatio besinS, quinine even in hectv doses, is no capable o preventin the multiplicatio of the plasmodium. Antolini, Golpi, Schaudino.
On the Semi-luna form quinine exercises no manifest action. The Semi-luna form represent a Sexua differentiatio of the prologoon