Document em5a6a91OK7a1Jqym2e47gV9E

rischc Ver- eUung dcr Laktat-De, ohl auf -dcr rotcin-Basi.s iigcliv War wur.dc cine tlcrotischcn Krgchnis.se swisscr Em genasc uml ekcnnzeich- rcccnt histo- i niveau ties r<t.) 82, 405. iinn rrmlaUia dospongieuf. bei der Oto Iqurne), Aca- 7., 36, 3.0. mical studies hie.), $2, 510. normal mat* in in malleus ip of co/iner* ociates, Wlcrest Ave,, S.A. i .JujariintiohilU'H OS, SA SU (lltCU) VII! NlvIiVK IN KX PEE I MENTAL LEAD POISONING Tk iik s a Go .z i)Zik -^Ol n ik h iu .-k w ic k and Bo g u s g a w Mo s z y n k k i From the 0tolari/ngolotjical Clinic, Warsaw, Poland putty healthy guinea pigs were poisoned with repealed peritoneal injerIions of lead acetale. After 7 weeks the animals were sacrificed and the inner ear with VIII nerve were examined histologically. The lead level in the blood was estimated in all animals after poisoning and in 10 healthy guinea pigs (control group). The sensory cells of the inner ear, the spiral and vestibular ganglion cells appeared to be normal. The VIII nerve in the majority of poisoned animals showed segmental deinyelinalion and axonal degeneration. Theories on etiology and pathogenesis of the ncuropatliological changes in lead poisoning are discussed. Among the many symptoms of lead poisoning are found complain Ls of iinlilory defects and vertigo (Giurlo & Ollohoni, 1950; Falkowska et /., I oil; GanumuToia <!fe Barlolt, 1964; Ursun & Suciu, 1965). The answer to the j.iMblcm of the toxic effect of the lead on inner ear and the VI11 nerve in ju.ni is still under discussion. Gambault (1880) was the first who demonrated peripheral nerve changes in guinea pigs resulting from lead poison tg. The next experiment reports described the influence of lead upon the > nlral nervous system and peripheral motor nerves (Ferraro & Hernandez, Fullerton, I960; Kornofsky & Ridgway, 1952; and others). The present work was undertaken to study the effect on the inner ear wnl VIII nerve after lead poisoning. METHOD Fifty healthy young guinea pigs were used for the experiment. Their a*-ihls ranged between 300 and 350 g. Ten guinea pigs served as a control *r the estimation of normal lead levels in the blood. Forty animals were m*u repeated doses of 1% solution of lead acetate Pb/N03/2.by intraperi' m*al injections. The total dose of 300 mg/kg was administered one time w ry 7 days during 7 weeks. Eight animals died before the end of the expert-h iiI. All remaining guinea pigs were weak and had lost weight. During the j"iM>uiag their growth was inhibited. The loss of weight is, according to f iiUnion (1966) and Causey (1965), a significant sign of serious poisoning. iilv five animals were able to run slowly, but they appeared to have mild r ralysis of their hind limbs. After seven weeks the animals were sacrificed, '- temporal bones removed for histopathological examination and the lead mi in the blood was estimated. The latter was determined in all animals Acta oto-laryng. 68 <s<> S / (J()zi)ZiK-ZoLNii:HKri.\vr(:z a n d Mu s z y n .s k i . . -r' '*. *:-... v ' rrv t<-*v..r,r/;%.** * r -.v;- '* *.r %-. . -. ' >,> * r 31 vi' * ` 'S -- nn.^ * *i** -S,* 'll b 7T ' jFisr. i. The VIII nerve from the poisoned guinea pig (cross section) stained by Sudan black B to show dcmyelination. The bundles of dcmyclinated fibres arc present in the center of the trunk; x 100. At the right of the figure the vestibular ganglion cells ate seen. Fig. 2. VIII nerve--single fibre from a poisoned animal stained by Heidenhain method (dr, b) and Sudan black B (c). (1) Segmental dcmyelination with the ovoids of degenerat ing myelin. (2) Intact myelin sheath. Magnification: (a) x 1000, (b) x 2500, (c) x 3200. after poisoning and in 10 healthy guinea pigs (control group). The estima tion of lead was made by a polarographic method similar to that described by Teisinger et al., (1956). The lead level in control group was 0.025 mg% 0.33 mg%. This level in the poisoned animals increased about 10 times to 0.31 mg% - 0.42 mg%. For histopathological examinations the animals were divided into two groups. The temporal bones of 16 guinea pigs (first group) after fixation and decalcification in EDTA were embedded in -celloidin, and sections were cut at 15-20 pt and stained with haematoxylin-eosin, cresyl violet and by silver impregnation method described by Gomori. The temporal bones from the remaining 16 guinea pigs (second group) were embedded in paraffin, because the application of methods to demon strate myelin and axon are limited by celloidin technic. Paraffin sections were stained by modified HeidenhahTs method, Sudan black B aiid luxol fast blue for myelin sheaths and Roger-FooPs method to demonstrate axons, RESULTS The histological investigations showed no pathological changes in the sensory cells of the inner ear or in spiral and vestibular ganglion cells. In Acta oto-Iaryng. 68 I i Fig. 3. VIII nc axons, x f)0. I he first gro animals wer nerve were 5 method. Tin tailed infori obtained by st rating my animals in remaining 1 (ion. On the cr when the nc spread to in fragments o tal (lemyelir the nerve. C ing myelin < Process o The degree i nerve. This poisoned gu the VIII ner DUP050044037 Lead Poisoning and Vtll Nerve 87 .... - J b c l by Sudan sent in the >n cells are ain method : degeiierat;) x 3200. ie estimadcscribed 55 mg%- ) times to rnals were rst group) oidin, and sin, cresyl ad group) to demonn sections and luxol ate axons. yes in the n cells. In fnj. X VIII nerve from normal guinea pig stained by Rogcr-Foot method to demonstrate axons. x GO, the first group (celloidin embedding) VIII nerves from 12 of the 16 poisoned animals were histologically abnormal. Focal changes with destruction of the nerve were seen in specimens stained by hematoxylin-eosm and by the silver im lhod. There was individual variation in the degree of these changes. De tailed information about the character of these pathological changes was obtained by histopathologicai examination with staining by methods demon strating myelin sheaths and axons. The VIII nerve of the 5 lead-poisoned animals in the second group was normal (Fig, 3). The VIII nerve of the remaining 11 guinea pigs showed both demyelination and axonal degeneralinn. On the cross section of the VIII nerve we observed characteristic changes when the nerve was stained by Sudan black B (Fig. 1). The demyelination spread to involve the nerve fibers in the centre of the trunk. Only residual fragments of myelin sheaths can be seen here. The various stages of segment;i) demyelination in a single fibre were observed also in remaning parts of tin* nerve. On the longitudinal sections (Fig. 2) several oyoids of degenerat ing myelin can be seen. Process of axonal degeneration in the same nerve is shown in Fig. 4. The degree and extent of these changes varied in different parts of the same nerve.. This distribution of the lesion prompts the suggestion that in leadpoisoned guinea pigs segmental demyelination and axonal degeneration of the Yltl nerve occur, Acta oto-laryny. 68 88 (i.OSfnZIK^OhNt KHKIKWICZ AND MOSZYNSKI %yx:*-rK\: $v"* ^; % & rn >Y J&jfc tv S < y x .' * ti^'\k #- J" iV ' *< ??< /O *' 'V - ,, _."' " ....:' >'. ., f* :r: ;4T !** -'v*' v *-': ' ^^r ,- -'?,; .,-. *. '*.' *) e**V .;** > * vy:OVy'f . . V>-- V/ <# * . ,r' '/' *1 > ` r:.v v? ,y> Ia*4t, ' v <V* - ~c * , , > * .* >' *T V#.; v-i ^ " ;' ^ ^ | *A fa Fig. ft. Axonal degeneration in VIII nerve from poisoned animal. Roger-Foot stain, (a) At the right of the figure is the region of total destruction of the nerve, x 400. (b, c) Axonal degeneration in single fibre at higher magnification, x 3200. DISCUSSION A full understanding of the pathogenesis of neiiropathological lesions produced by lead has not emerged* The theory which was supported for many years is that of porphyrin metabolic deficiencies. Some authors have stressed damage to the vascular epithelium, suggesting that the neuropathologicai lesions may be secondary to the vascular (Cumings, 1959; Ursan & Suciu, 1965), The predominant changes in the central nervous system were found by other workers. In previous experimental works on chronic lead poisoning, demyelination of the nerve fibers was found (Fullerton, 1966; Glees, 1961). This toxic effect is probably the result of disturbance to the enzymatic content of mye lin sheath. The degeneration of myelin may also be the result of the degene ration of the axis cylinder. These biochemical lesions produced by heavy metals were stated by Glees (1961). The striking resemblance of the early neurological symptoms of chronic lead poisoning in man to those seen in other demyelinating syndromes suggest that this is the same etiological agent. For this reason some authors have suspected lead as a possible cause of multiple sclerosis (Campell, 1950; Cone et al., 1934; Falkowska et al, 1964). Our work showed that lead poisoning in guinea pigs might produce chronic, demyelinating neuropathy of the VIII nerve with axon degenera tion. The sensory cells of the inner ear have been found to be most resistant to the toxic effect of lead. The degree of the histopathological changes is not necessarily the same in different animals. This finding suggests the indi vidual sensitivity to lead intoxication and confirm other experimental and el iniral observe1ions. A via oto-largng. 68 , The results to lead i atoxic lesionsv I)jc lotersucl diirchgefiihrt. II von Bleiazetat a gi flung wurden hisiologiscli uni schweinchen, d xtimnit. Die Sin Ganglions sowh tier vergifteten und cine Axond falls die besteh* gischcn Veriinde Campbell, A. M., 1 Causey, G,, 1065; (Viurlo, E., and Otl Excerpta Med., ('.one, W,, Russel, Arch. Neurol. I Cumings, J. N., If ford. Falkowska, Z,, S< zmianami w O; Ferraro, A., and I nervous system 6, 319. Fullerton, P. M., guinea-pigs. /.. Gnmbault, M., 138 subaigue et chr (iuinmarrota, M., . saturnina e def Clecs, P., 1961; Ex Kornofsky, D. A., i system of the c Teisinger, J., Skrai iogickeho v pru Ursan, and Su industrial lead Hcceived October 1 DUP050044039 (a) At Axonal Lead Poisoning and VIII Nemo 89 The results of our experiment in guinea pigs are relevant with reference in lead intoxication in man, hut may suggest the pathogenesis of VIJI .nerve lesions. ZUSAMMKNPASSU NG Dir rntersuchungen warden an 40 gesunden, jnngen, weissen Meerschweinelien *lurrligefUliri. Die Mcersdiweinchen wurdcii iiiittcls intraperUonealer Injekfion.en von IHciazetat allniuhlieh vergiftet. Nach ciner 7 Wochen lang anclauernclen Vergiftung warden die Tiere gelotet und das Iimenohr sdwie der VIit. Jlirnnery liislologisch ludersiidtt. Bei alien vergifteten Tieren und bei 10 gesunden Meurwhwcinclien, die als Kontrollgruppe dienten, wurde der Bleigchalt im Blut bediimiit. Die Simieszelleii des I mien ohres und die Nervenzellcn des vestibuliiren ganglions sowic des Ganglio spiralc cochleae waren normal. Bei der Mchrzahl icr vergifteten Tiere wurde ini VILI. Hirnnerv cine segmentiire Deniyelinisation nml einc Axondegeneration festgestellt. In der vorliegenden Arbeit warden gleichf.ills die bestohenden Auffassungen iiber die Atiopatliogenese der neuropatliologischen Verandcrungen bei Vcrgifttingen dargclcgt. esions 3.d for ; have >athosan <& . were ia lion toxic mycigeneheavy ironic 'OlllCS thors 1950; j ) I f 1 I J | }duce nerastant jes is indil and | 1 1 REFERENCES (,mphell, A, M., 1950 ; Lead in relation to disseminated sclerosis. Brain, 73, 52. (G., 1965; Tissue distribution of intravenous lead. Brit. J. Cancer, 19, 867. i.iurlo, B., and Ottoboni, A., 1956: Variation of the internal ear in chronic lead poisoning. Excerpta Med,, 9, 60. t <>iu\ W\, Russel, C*, and Harwood, R., 1934: Lead as possible cause of multiple sclerosis. Arch* Neurol. Psych., 31, 326. i innings, J. N\, 1959: Heavy metals and the brain. Blackwell Scientific Publication, Ox ford. I .ilko.w.ska, Z., Sobkowicz, H., and Tur, J., 1964: Przypadek przewleklej otowiey zc zmianami w Osr, Ukt. Nerw. i nnrzqdzic wzroku. Pol. Tyg. Lek., 19, 1215. i viniro, A., and Hernandez, R., 1932; Lead poisoning. A histopathological study of the nervous system of cats and monkeys in the acute and subacute stages. Psychiat. Quart., r>, 319. i ullcrlon, P. M., 1966: Chronic peripheral neuropathy produced by lead poisoning in guinea-pigs. /. Neuropath. Exp. Neurol., 25, 214. o.utibniiH, M., 1880: Contribution A l'dtude anatomique de la nevrite parenchymateuse Mihaigue et chronique-ndvrite segmentaire peri-axile. Arch. Neurol. (Par.), 1, 11. 'i.iininarrota, M., and Bartoii, E., 1964: Considerazioni sui rapporti tra intossiciazione >;durnina c defficit cocleare. Clin. Otorinolaring. (Roma), 16, 136. '-lies, P., 1961: Experimental Neurology. Clarendon Press, Oxford. Hornofsky, D. A., and Ridgway, ;L. P,, 1952: Production of injury to the central nervous system of the chick embryo by lead salts. J. Pharmacol. Exp. Ther., lOh, 176. Uisinger, J,, Skramovsky, H., and Srbowa, J>, 19,56: Chemice methody k vysetrovani bio- togiekeho v prumyslowe toxikologii. S. Z. N., Praha. } rs;m. G., and Suciu, ,T., 1965: Notes on modern aspects of neurotoxicosis in chronic industrial lead poisoning. J. Uyg, Epidcm. (Praha), 9, 409. x October 19, 1968 Klin ika Otolaryngologiczna, ul. Nowogrodzka 59, Warszawa, Poland Ada oto-laryng. 68 i { i' DUP050044040