203 Toxicity of aerosolized aprotinin in animals

203 TOXICITY OF AEROSOLIZED APROTININ IN ANIMALS A. V. Ovcharenko, P.B. Gol yando, O.P.Zhi rnov, T.P. Svi nogeeva, G. V. Dol gova, A.V. Ni ki t i n The D.I.Ivanovsky Virology Institute, Moscow 123 098, State Research Center of Antibiotics, Moscow 113 105, Russia In animal models of Flu A and paramyxovirus infections, the aerosol delivery of aprotinin has been shown to be therapeutically superior to parenteral administration. The t o x i c i t y of aerosolized aprotinin (Contrycal - AWD, Germany) in young rats (50-60 g), adult rats (150 g), rabbits, and guinea pigs was studied. The aerosol mist was generated by an ultrasonic nebuliser ( Musson-1; Trade Mark N25-2012; Altay Instrumental Plant, Russia) and was delivered to animals by means of f i t t i n g muzzle masks. The animals received 10-15 min inhalations of aprotinin daily for 30 days. As calculated on the basis of human-animal lung ventilation and body surface ratio, such regimen corresponds to 120 min inhalation a day for man. The aprotinin aerosol was highly tolerated by animals and the inhalations did not change the behaviour of animals. No significant changes occured in biochemical and hematologic values of blood; microscopic, morphometric, and histologic analysises of animal organs; cardiologic examination; the functional examination of CNS and psychometer tests. The inhalation of aerosolized aprotinin failed to possess a local i r r i t a n t action and allergent reactions both active and retarted types. These d a t a show that aerosolized aprotinin has no adverse side effects and provide clear rationale and safety for i t clinical trials as antiviral against respiratory Influenza-like i nfecti ons.

204 Guinea Pig as a Model for Study of Marburg Virus Interractlon w i t h Mononuclear Phagocytes A.A.Skripchenko,*E.I.RJabchikova,*A.M.Shestopalov. Alrblology Division,*Virology Division, Institute of M o l e c u l a r B i o l o g y SPA " V e c t o r " , Koltsovo, Novosibirsk region, Russia. The s t u d y o f interaction of Marburg v i r u s with cells o f MPS ( m o n o n u c l e a r p h a g o c y t i c s y s t e m ) o f g u i n e a p i g s u s i n g complex of v i r o l o g i c methods and e l e c t r o n microscopy was c a r r i e d out. Active reproduction of Marburg v i r u s in peritoneal macrophages i n v i t r o and in vivo was revealed. Performed study showed t h a t cells of MPS were t h e ~irst target-cells of guinea pigs intraperitoneally infected with Marburg virus. Virus multiplication i n macrophages enhanced a ~ t e r t h e infection of the latter in the presence o~ the specific antiserum. Cells o f MPS p r o v i d e d the virus dissemination into interstitial tissue of internals. Analysis of obtained data testified that viral alteration o~ MPS cells play important role in p a t h o g e n e s l s o f d i s e a s e caused by M a r b u r g v i r u s .

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