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Tissue and blood distribution toxicologically active compounds from castor bean (Ricinus communis L. 1753, Euphorbiaceae) and their forensic importance

dc.contributor.advisorPilija, Vladimir
dc.contributor.otherDrašković, Dragan
dc.contributor.otherMatejić, Suzana
dc.contributor.otherVasović, Velibor
dc.contributor.otherStojiljković, Goran
dc.contributor.otherVuković, Radenko
dc.creatorRadosavkić, Radosav
dc.date.accessioned2017-10-09T14:21:41Z
dc.date.available2017-10-09T14:21:41Z
dc.date.available2020-07-03T13:24:47Z
dc.date.issued2017-09-28
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija149578577735128.pdf?controlNumber=(BISIS)104726&fileName=149578577735128.pdf&id=9899&source=NaRDuS&language=srsr
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/8650
dc.identifier.urihttp://www.cris.uns.ac.rs/record.jsf?recordId=104726&source=NaRDuS&language=srsr
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije14957858037040.pdf?controlNumber=(BISIS)104726&fileName=14957858037040.pdf&id=9901&source=NaRDuS&language=srsr
dc.description.abstractRicin je prirodni protein, toksin koji spada među najpristupačnije i najsmrtonosnije otrove. Nalazi se u biljci Ricinus (Ricinus communis), sa najvećim sadržajem u semenu (1-5 %). Ricin se smatra potencijalnim bioterorističkim oružjem i prema riziku za ljudsko zdravlje svrstan je u B kategoriju biološkog oružja. U novije vreme korišćen je za konstruisanje imunotoksina protiv tumorskih ćelija u terapiji maligniteta. Dokumentovana su mnoga trovanja ricinom, kako zadesna, tako i samoubilačka i ubilačka. U tu svrhu koristilo se intaktno seme ricinusa ili ekstrahovani ricin. Osim ricina, u semenu ricinusa je prisutan toksični alkaloid ricinin u količini 0.3-0.8 %. Ricinus je jedini poznati prirodni izvor ricinina, koji se ko-ekstrahuje sa ricinom iz semena biljke. Ricinin se jednostavno detektuje u kliničkim uzoracima metodom tečne hromatografije i masene spektrometrije i, s obzirom na komplikovanu identifikaciju ricina u biološkim uzorcima, smatra se biomarkerom za intoksikaciju ricinusom, odnosno ricinom. Osnovni ciljevi ovog istraživanja su da se uz pomoć HS-GC metode i patohistološkom  analizom dokaže prisustvo ricinina u krvi laboratorijskih pacova u odnosu na vremenski interval koji je protekao od oralne aplikacije suspenzije do vremena žtvovanja, da se odredi distribucija i koncentracija ricinina u organima laboratorijskih pacova u različitim vremenima žrtvovanja, kao i da se utvrdi da li postoji značajna razlika u razvoju patomorfoloških promena na organima laboratorijskih pacova u različitim vremenima žrtvovanja. Istraživanje je bilo otvoreno, randomizirano i prospektivnog tipa. Laboratorijski pacovi su u istom vremenu oralno tretirani suspenzijom koja je sadržaja subletalnu koncentraciju ricina. Nakon žrtvovanja u precizno definisanim vremenskim intervalima uzeti su uzorci krvi i unutrašnjih organa radi daljih analiza. Odgovarajući uzorci su analizirani metodom HC-GS u cilju određivanja koncentracije i distribucije ricinina, kao pouzdanog markera trovanja ricinom, u krvi i unutrašnjim organima. Takođe je izvršena patohistološka analiza uzoraka tkiva unutrašnjih organa u cilju utvrđivanja promena izazvanim delovanjem ricina u odnosu na vreme proteklo od aplikacije suspenzije. Dobijeni rezultati su obrađeni odgovarajućim statističkim metodama. Rezultati istraživanja omogućavaju standardizaciju postupaka odabira reprezentativnih uzoraka prilikom sumnje na trovanje ricinusom i metode dokazivanja akutnog trovanja. Na taj način može se pouzdano i efikasno dokazati trovanje ricinusom.sr
dc.description.abstractRicin is a naturally occurring protein, a toxin which belongs to the category of the most accessible and the most lethal poisons. It is obtained from the castor oil plant ( Ricinus communis), whose seeds contain its highest content (1-5%). Ricin is also thought to be a potential weapon of bioterrorism and taking into account the risk for human health, it is classified as a biological weapon category B. Lately it has been used for the construction of the immunotoxins against tumor cells in the therapy of malignant diseases. Numerous poisonings using ricin have been documented, not only accidental poisoning, but also in case of suicides and homicides. In those cases, intact ricin seeds or extracted ricin were used. Apart from ricin, castor oil plants also contain a toxic alkaloid ricinine (0.3-0.8%). Castor oil plants are the only known natural source of ricinine, which is co-extracted with ricin from the seeds of this plant. Ricinine is simply detected in clinical samples by using the method of liquid chromatography and mass spectrometry. Taking into account a complicated identification of ricin in biological samples, it is considered to be a biomarker for the intoxication by castor oil plant, or ricin itself. The main aim of this research is to use the HS-GC method and pathohistological analysis in proving the existence of ricinine in the blood of experimental rats in relation to the time interval between the oral application of solution of castor seeds in water and the time of sacrificing, to determine the distribution and concentration of ricinine in the organs of experimental rats, as well as to establish whether there was a significant difference in the development of pathomorphological changes on the organs of experimental rats at various points of sacrificing. The research was open, randomised and prospective. Experimental rats were simultaneously orally tested by the solution which contained sublethal concentration of ricin. After sacrificing, blood samples were taken from inner organs in specifically defined intervals of time and used for further analysis. The appropriate samples were analysed by HC-GS method in order to determine the concentration and distribution of ricinine as a reliable marker of ricin poisoning in blood and inner organs. Also, pathohistological analysis of the samples of inner organ tissues was made with the purpose of establishing the changes caused by the effects of ricinine in relation to time which passed from the application of the solution. The obtained results were processed by appropriate statistical methods. The results of this research allow for the standardisation of the actions in selecting the representative samples in case there is a possibility of ricin poisoning and the method of proving the acute poisoning. Following these steps, ricin poisoning can be proved in a reliable and an efficient way.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectricinussr
dc.subjectRicinusen
dc.subjectLaboratoryen
dc.subjectricinsr
dc.subjectalkaloidisr
dc.subjectforenzička toksikologijasr
dc.subjecttoksokinetikasr
dc.subjectgasna hromatografija-masena spektrometrijasr
dc.subjecttrovanje biljkamasr
dc.subjectmorfološke i mikroskopske promenesr
dc.subjectlaboratorijske životinjesr
dc.subjectautopsijasr
dc.subjectsudska medicinasr
dc.subjectAutopsyen
dc.subjectForensic Medicineen
dc.subjectRicinen
dc.subjectAlkaloidsen
dc.subjectForensic Toxicologyen
dc.subjectToxicokineticsen
dc.subjectGas Chromatography-Mass Spectrometryen
dc.subjectPlant Poisoningen
dc.subjectMorphological and Microscopic Findingsen
dc.subjectAnimalsen
dc.titleTkivna i krvna distribucija toksikološki aktivnih jedinjenja iz ricinusa (Ricinus communis L. 1753, Euphorbiaceae) i njihov sudskomedicinski značajsr
dc.title.alternativeTissue and blood distribution toxicologically active compounds from castor bean (Ricinus communis L. 1753, Euphorbiaceae) and their forensic importanceen
dc.typedoctoralThesissr
dc.rights.licenseBY-NC-ND
dcterms.abstractПилија, Владимир; Драшковић, Драган; Матејић, Сузана; Васовић, Велибор; Стојиљковић, Горан; Вуковић, Раденко; Радосавкић, Радосав; Ткивна и крвна дистрибуција токсиколошки активних једињења из рицинуса (Рицинус цоммунис Л. 1753, Еупхорбиацеае) и њихов судскомедицински значај; Ткивна и крвна дистрибуција токсиколошки активних једињења из рицинуса (Рицинус цоммунис Л. 1753, Еупхорбиацеае) и њихов судскомедицински значај;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34160/IzvestajKomisije11500.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34159/Disertacija11500.pdf


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