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Anais Brasileiros de Dermatologia

On-line version ISSN 1806-4841

An. Bras. Dermatol. vol.78 no.1 Rio de Janeiro Jan./Feb. 2003

http://dx.doi.org/10.1590/S0365-05962003000100002 

CONTINUING MEDICAL EDUCATION

 

Prionic disease: evaluation of the risks involved in using products of bovine origin*

 

 

Omar Lupi

Post-PhD. from the University of Texas (UTMB). Masters and Ph.D. in Dermatology, UFRJ. Adjunct Professor of Dermatology and Immunology, IPGMCC/PGRJ. Assistant Professor of Dermatology, UGF. On license from the Dermatology Service, HUCFF/ UFRJ and UGF

Correspondence

 

 


SUMMARY

A prion is a protein that is capable of self replication, thereby altering a cell's metabolism. It is responsible for a number of human and animal diseases (prionic diseases), all of which are always lethal. These diseases have enormous variability in their incubation periods, ranging from a few months to forty years. Prions accumulate and destroy nerve cells, causing spongiform encephalopathy. We discuss the clinical picture, epidemiology, and historical background of prionic diseases. The major focus of the discussion lies, however, on the theoretical possibility of iatrogenic transmission of prion infection due to topical formulations using ceramides (cerebrosides) or placenta of bovine origin, as well as the risk represented by some dermatological procedures such as skin grafts and collagen implants.

Keywords: ceramides; dermatology; encephalopathy, bovine spongiform; prions.


 

 

INTRODUCTION

The concept of prionic diseases, as proposed by Stanley B. Prusiner,1 presupposes the existence of a new notion in biology, known as the "prion hypothesis" (proteinaceous infectious particles). This concept was considered heretical at that time for supposing the existence of infectious diseases caused by agents without nucleic acids.

Since the pioneering works of Watson and Crick in 1953, it has been considered that deoxyribonucleic acid (DNA) is the organic molecule capable of storing biological information, using for this the nucleotides adenine, thymine, cytosine and guanine. Such nitrogenous bases group in pairs and using a binary code are capable of storing the correct sequence of amino acids that compose each protein or enzyme responsible for maintenance of the metabolism, growth and reproduction. According to the definition of Maturana and Varela,2 DNA is the code that sustains all of the known living systems, by enabling autopoiesis.

The molecule responsible for carrying this codified information from the nucleus to the cytoplasm is ribonucleic acid (RNA), and the final product of this chain of events is the protein. A dogma of modern biology considers that the flow of biological information must, necessarily, follow this sequence of events. The only form of known life capable of partially subverting this system is the retrovirus (HIV, HTLV), which uses the reverse transcriptase enzyme to synthesize DNA from RNA. Some rare RNA-viruses and viroids (infectious pathogens of plants) only use RNA as a system encoder, without requiring DNA to synthesize proteins.

The prion hypothesis ignored the so-called "central dogma of biology" by accepting that protein particles are able to directly produce diseases without the apparent participation of any nucleic acid, whether this is DNA or RNA.1 This work presents the possible repercussions of these new pathogens in dermatology, with special focus on the risk presented by the topical use of products derived from bovine cerebrosides (ceramides) and the placenta, as well as some dermatological procedures that involve products potentially infected by prions.

 

BACKGROUND

The first historical appearance of prionic diseases was seen 200 years ago, according to McGowan,3 with the recognition of a dermatological and neurological disease with fatal course in sheep. The zoonosis known by sheep farmers as "scrapie" is characterized by the appearance of a constant itch that leads the infected animals to scrub themselves on fences or trees, followed by loss of the wool and development of a dermatitis very similar to pictures of subacute and chronic eczematization. It is possible that both the areas of alopecia and lichenification with crusts are a consequence of the repeated scrubbing action by the animal to relieve the itch. The term scrapie comes from the English word scrape. The most typical characteristic of the disease is its course, after a period varying from six months to two years, leading to progressive ataxia, motor paralysis, tremors, fasciculation and death.4 An infectious agent was always suspected due to the appearance of epidemic focuses, but this agent was never successfully isolated.3. Experimental studies have demonstrated the possibility of transmission of the disease to other healthy sheep and also to goats of both sexes.4 Histopathological analysis of the brain of these animals presented extensive amyloid deposits and neuronal rarefaction, in a similar form to that of Alzheimer's disease in humans.3,4

Zigas and Gajdusek observed the appearance of a rare neurological disease in some tribes of New Guinea.5 A more detailed study, carried out among the Fore tribes, demonstrated the existence of an aggressive and mortal neuropathy known by the local inhabitants as kuru (laughing death).6 The disease presented a mean incubation period of several months, causing death induced by insanity, progressive ataxia and blindness. Incapable of eating, the individual succumbed, victim of dehydration, malnutrition and opportunist infections. kuru was demonstrated to be a disease practically restricted to the elderly, women and children, while sparing men. It was discovered that the first cases dated back to the 1920's, when motivated by a sudden shortage of food, the Fore tribes started to perform cannibalistic feasts.5,6 In such ceremonies, the warlike youths ate the muscles, as these symbolized the dead person's strength, leaving the viscera, bone marrow and brain for the other inhabitants. Histopathological analysis of the brain of aborigines that died from kuru demonstrated an impressive similarity to scrapie.6 The progressive abandoning of cannibalism on the part of Fore resulted in the control and eradication of the disease by the end of the 1960s. The infectious properties of the kuru agent were demonstrated by experimental transmission of the disease to chimpanzees.7

Other prionic diseases were later recognized as such, even though for many years they had been grouped under a generic and imprecise nomenclature of "diseases induced by slow virus" or "spongiform encephalopathies" (Table 1). Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS) are rare neurological diseases, known since the twenties in Europe.8,9 Besides presenting a picture of ataxia and insanity, they also demonstrate a similar anatomicopathological pattern to kuru.10 Recently described,11 fatal familial insomnia (FFI) affects nine families in the world and also develops the same anatomicoclinical picture. In spite of the pattern of familial inheritance in all of these, sporadic (mutations) and same iatrogenic cases can occur.11,12 They are a unique and apparently paradoxical example of diseases that are genetically determined, but can be experimentally transmitted to guinea pigs.

No great interest was given to this rare group of neurological diseases until the appearance, in the 1980s, of bovine spongiform encephalopathy (BSE), more commonly known as "mad cow disease". This new disease developed in an epidemic manner in England, leading to the death of about 180,000 animals since 1985.13,14 Again, histological analysis of the brain of sick animals enabled the detection of the pattern already observed in other prionic diseases.14 Initially, BSE was limited to the United Kingdom and countries that imported its cattle.15 The English National Institute of Health discovered that the appearance of such cases coincided with a modification in the strategy for feeding cattle in England.16 Seeking to increase the productivity and weight gain, cattle farmers began to use biological refuse from the cattle themselves, such as placentas and recycled carcasses, in order to increase the protein content of the rations.15,16 The similarity with kuru is impossible to ignore, in view of the transmission of the disease through feeding.5,6

The theoretical fear that BSE could be transmitted to human beings by the ingestion of bovine meat was confirmed in 1995. A new neurological disease that resembled CJD, but presented a faster course than kuru, was detected in humans and denominated new variant of CJD (nvCJD).17,18 From the first case registered to mid 2001, 107 contaminated individuals have been notified, of which 102 in the United Kingdom, three in France, one in Ireland and another in Hong Kong.15 The incubation period of nvCJD is unknown, but in general death occurs within 15 months.(Table 1).19

 

THE PRION HYPOTHESIS

During decades biological material has been studied originating from animals and humans infected with prionic diseases, without ever having isolated an infectious agent. Electron scanning microscopy, capable of detecting the smallest known viruses, only revealed the presence of abnormal amyloid deposits.20 Samples of contaminated tissue were exposed to ultraviolet radiation, heat (up to 170º C), nitric oxide, hydrogen peroxide and hydroxylamines or enzymes capable of fragmenting nucleic acids (nucleases), but without the agent losing its infective capacity.20,21 Even though these procedures are effective in the destruction of all of the known fungi, bacteria, chlamydia and viruses (RNA or DNA).

Another very peculiar aspect of the disease concerns the fact that material originating from sheep can infect mice, monkeys and other animals, without respecting any barrier between the species.21,22 Since the invasion of the target cell is usually specific to each species or correlated species, as it depends on receivers of the cellular membrane, it was concluded that prionic diseases are caused by a new class of infectious agents, smaller still than the viruses and, apparently, without DNA or RNA.

Agents capable of denaturing proteins, however, were effective in reducing the infectivity.20 Samples exposed to phenol, diethyl pyrocarbonate (DEP) or thiol proteases stopped transmitting the disease. The only possible explanation was that, in some way, proteins alone were capable of provoking these neurological pictures. However, every search for foreign proteins also proved unproductive.21

Prusiner1 then developed a new concept, in which a protein of the host itself became infectious (prion) by changing its spatial configuration. A considerable proportion of the biological activity of a molecule depends on its structural form. DNA, for instance, only manages to codify information if it is in its double spiral form. It is known today that the prion gene (gene 20p12.3), located in the short branch of chromosome 20, codifies an important protein (PrP) in the transmembrane signaling functions.20-22 A mutation of this gene produces an aberrant isoform (scrapie PrPSc) that is extremely stable and has an impressive capacity to modify the spatial structure of normal PrP with which it has contact. Both are exactly the same in terms of their sequence of amino acids, except for the fact that PrPSc presents a prevalence of beta sheets, to the detriment of alpha sheets.1,10,20,22

It is believed that CJD can be caused by eventual mutations (sporadic cases), but it can also be familial (previous mutations that come to be transmitted genetically) or iatrogenic (contaminated surgical material, transplant of dura mater and corneum as well as cadaveric growth hormone).22 The cases of GSS and FFI present the same pattern, except for the iatrogenic transmission, which has not yet been observed 10-12 (Table 1). Kuru appeared, probably as a result of a spontaneous mutation of CJD type in an aborigine of New Guinea, but, due to cannibalism, the foreign protein was disseminated among the island's population.12 The first case of BSE must have appeared in a similar manner, since the prions form a group of proteins present in all vertebrates.4 It was disseminated among cattle by the artificial cannibalism induced by farmers.16 The epidemiological chain continued with human contamination after consuming bovine meat (nvCJD).18 Given that the incubation period of the prionic diseases can be very long (Table 1), it is believed that many new cases of nvCJD will emerge in the following months or years.19

 

RISKS FROM PRODUCTS OF BOVINE ORIGIN

The risk presented by nvCJD, whether by accidental transmission or new varieties of prionic diseases is very far from being controlled by the sacrifice in mass of European cattle and implementation of more rigorous and controlled techniques for their feeding.19 One of the reasons for this is that a safe means of sterilization against prions has yet to be discovered. There are works demonstrating that they are very resistant to UVC and autoclave, remaining viable after one hour of exposure to a temperature of 360°C.21 It is now admitted that a safe procedure of sterilization for materials contaminated by prions would have to involve immersion for one hour in sodium hydroxide 2N, followed by autoclave for another hour. All material that can not be autoclaved should be promptly incinerated.23

Another factor that can influence the appearance of new cases is the widespread use of tissue of bovine origin in foods and also pharmaceutical and manufactured products.24 (Table 2). Besides the obvious use of bovine meat for alimentation, several other tissues or organs and several of the proteins and bovine enzymes are economically important.24 Many of those products are processed chemically, such as glycerin and the glycerol present in medicine capsules, suppositories and vehicles for topical application. Such derivatives present, in general, a low risk for the presence of prions. Others, however, such as catgut and collagen implants are used almost in natura and could present a real risk of spreading disease.25 Several of the hormones and bovine enzymes, such as insulin and heparin, would be denatured if submitted to heat or the chemical treatment necessary for their sterilization. Hence, they would lose their potential for biological use. Other products, such as fetal bovine serum (FBS), newborn calf serum (NCS) and bovine trypsin, are fundamental ingredients for the maintenance of cell cultures that produce cultivated skin for grafts or collagen for intradermal implants. The authors recently suggested that any one of these biological products originating from cell cultures infected by prions would theoretically be able to transmit the disease.25

Since PrPSc is a protein of the host itself, presenting exactly the same antigenic determinants as their normal counterpart (PrP), it is not immunogenic to the host. This can disable the serological diagnosis of the disease and considerably hinders the laboratorial evaluation of possibly contaminated patients, animals and materials.22

Neither BSE nor scrapie affects all bovine tissues with an equal frequency.26 The preference is well-known for the central nervous system and eyes; tissues considered to be of high risk.17,18,26 Among the organs of medium risk are the spleen, tonsils, lymph nodes, intestine, liquor, suprarenal glands, placenta and dura mater. In the category of moderate risk are bone marrow, liver, lungs, pancreas and thymus. While cardiac tissue, milk of bovine origin, bones and genitourinary system are considered to be low risk.17,18,26 There is much controversy regarding the risk presented by vaccines of bovine origin, but the notion still prevails that, in this case, the benefits far exceed the risks.27,28

There still does not seem to be a satisfactory risk evaluation for skin and material of dermal origin. However, Pammer and cols,29 have detected the expression of PrP in both normal and affected skin for several dermatoses, such as eczema, psoriasis and leg ulcers. The presence of normal prionic protein in the skin allows, theoretically, contamination by the use of topical or intradermal products, since it is tissue that expresses PrP. In fact, as a result of its extension, wealth of macrophages and frequent trauma, the skin represents an excellent entrance site for prionic infections, as was already suspected by Gajdusek and Zigas6 when they studied kuru.

Since the beginning of this year, the United States and several Asian countries have banned for an indefinite period all cosmetic products of bovine origin exported by European Union countries.30 The ban seeks to avoid the commercialization of cosmetics derived from bovine collagen and placenta, reinforcing once again the considerable risk the latter presents in the transmission of BSE.26 The main objectives of this blockade, however, are various cosmetic products containing ceramides.30 Although these comprise only about 10% of the total mass of corneum extract, the ceramides are an essential component of the epidermal barrier.31 Together with cholesterol and the free fatty acids, they compose a hydrolipid intercellular layer that reduces the transepidermal loss of water and constitutes an adequate protection against exogenous irritants and cutaneous infections.31 Ceramides of bovine and porcine origin are used in many of the topical formulations available today. However, it should be underscored that such ceramides are derived from a group of molecules known as cerebrosides.31 The ceramides form a particularly heterogeneous and complex group of sphingolipids, containing the sphingosines (types 1, 2, 4 and 5) and phytosphingosines (types 3, 6I and 6II).31 The risk from the use of these substances is obvious, considering that the skin is an organ that effectively expresses PrP and nervous tissue, the natural reservoir and replication site of the prionic protein.22,29

One should also consider that animal tissue of other origins, such as porcine and avian, also present a risk for transmission of prionic diseases. This occurs due to the techniques involved in recycling animal protein by modern farming. Carcasses and tissue of low commercial value are triturated and ground, but not sterilized, and then used to enrich the rations for these animals, exactly as in the case of cattle.16 The apparent nonexistence of cases in pigs, chickens and other animals used for human foodstuffs could just reflect the precocious slaughter or sub-notification of diseases involving these animals. This could actually be an aggravating factor, given that any animals dying before the habitual time for slaughter are immediately recycled as ration and consequently could create the positive feedback which generates a mass infection of these animals.

 

CONCLUSION

The recent discovery of prions as infectious agents has been modifying the current concepts regarding feeding and use of tissues of animal origin for human beings. Biological barriers between the species, which restricts the spread of other types of pathogen, seem to have little affect against the spread of prionic diseases. The long incubation period of these diseases, sometimes measured in decades, does not allow one to reach more exact conclusions regarding the extension of human contamination. The fact is that the majority of techniques once considered to be very safe, such as sterilization protocols and recycling of animal protein, are being reviewed. It seems wise, therefore, to take similar measures regarding the use of animal products in implants, sutures and topical formulations.

 

ACKNOWLEDGEMENTS

This work was done with the support of the CNPq - Brazil (National Council for Scientific and Technological Development) project nº. 200868/00-4 (Post-PhD Abroad).

 

REFERENCES

1. Prusiner SB. Molecular biology and pathogenesis of prion diseases. Trends biochemical Sciences 1996; 21 (12): 482-7.        [ Links ]

2. Maturana HR, Varela FJ. The tree of knowledge. 1987. Boston, MA. Shambhala Publications.        [ Links ]

3. McGowan JP. Scrapie in sheep. Scott J Agric 1922; 5: 365-75.        [ Links ]

4. Balter M. Origins of BSE. Intriguing clues to a scrapie-mad cow link. Science 2001; 292 (5518): 827-9.         [ Links ]

5. Zigas V, Gajdusek DC. Kuru: clinical study of a new syndrome resembling paralysis agitans in native of the Eastern highlands of Australian New Guinea. Med J Aust 1957; 2: 745-54.        [ Links ]

6. Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea: the endemic occurance of kuru in the native population. N Engl J Med 1957; 257: 974-8.        [ Links ]

7. Gajdusek DC, Gibbs CJ, Alpers MP. Experimental transmission of kuru-like syndrome to chimpanzees. Nature 1966; 209: 794-6.         [ Links ]

8. Creutzfeldt HG. Uber eine eigenartige herdformige Erkrankung des Zentralnervensystems. Z Gesamte Neurol Psychiatr 1920; 57: 1-18.        [ Links ]

9. Jakob A. Uber eigenartige Erkrankungen des Zentralnervensystems mit bemerkenswertem anatomichen Befunde (Spastische pseudosklerose-Encephalomyelopathie mit disseminierten Degenerations-herden). Z Gesamte Neurol Psychiatr 1921; 64: 147-228.        [ Links ]

10. Piccardo P, Liepnieks JJ, William A et al. Prion proteins with different conformations accumulate in Gerstmann-Straussler-Scheinker disease caused by A117V and F198S mutations. Am J Pathol 2001; 158 (6): 2201-7.        [ Links ]

11. Delisle MB. Fatal Familiar Insomnia. Clin Exp Pathol 1999; 47 (3-4): 176-80.        [ Links ]

12. Collins S, McLean CA, Masters CL. Gerstmann-Straussler-Scheinker syndrome, fatal familiar insomnia, and kuru: ofthese less common human transmissible spongiform encephalopathies. J Clin Neurosci 2001; 8 (5): 387-97.        [ Links ]

13. Adam D. Review blames BSE outbreak on calf feed. Nature 2001; 412 (6846): 467.        [ Links ]

14. Bosch X. European concern over BSE transmission. JAMA 2001; 285 (4): 397-8.        [ Links ]

15. Cousens S, Smith PG, Ward H et al. Geographical distribution of variant Creutzfeldt-Jakob disease in Great Britain. Lancet 2001; 357 (9261): 1002-7.        [ Links ]

16. Dobson R. Traditional butchery methods linked to vCJD clusters. Br Med J 2001; 322 (7289): 753.        [ Links ]

17. Coulthart MB, Cashman NR. Variant Creutzfeldt-Jakob disease: a summary of current scientific knowledge in public health. CMAJ 2001; 165(1): 51-8.         [ Links ]

18. Calza L, Manfredi R, Chiodo F. Epidemics of BSE and nvCJD in humans. Most recent findings on prion diseases. Recenti Prog Med 2001; 92 (2): 140-9.        [ Links ]

19. Beale AJ. BSE and vCJD: what is the future? JR Soc Med 2001; 94 (5): 207-9.        [ Links ]

20. Rudd P, Wormald MR, Wing Dr et al. Prion Glycoprotein: Structure, Dynamics, and roles for the sugars. Biochemistry 2001; 40 (13): 3759-66.        [ Links ]

21. Appel T, Wolff M, von Rheinbaben F et al. Heat stability of prions rods and recombinant prion proteins in water lipid and lipid-water mixtures. J Gen Virol 2001; 82: 465-73.        [ Links ]

22. Collinge J. Prion diseases of humans and animals: Their cause and molecular basis. Annu Rev Neurosci 2001; 24: 519-50.        [ Links ]

23. Prakash B. Sterilization of prions - Agents of transmissible degenerative encephalopathies. Bull Hosp Infect Soc India 1996; 1 (1): 23-4.        [ Links ]

24. Karezouni N, Sinha R, Hsu CH et al. Analysis of 200 food items for benzo[a]pyrene and estimation of in an epidemiologic study. Food Chem Toxicol 2001; 39 (5): 423-36.        [ Links ]

25. Lupi O. Prions in dermatology. J Am Acad Dermatol 2002; 46 (5):790-3.         [ Links ]

26. Race RE, Ernst d, Jenny A, et al. Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen and lymph nodes: Implications for transmission and antemortem diagnosis. J Infect Dis 1998; 178: 949-53.        [ Links ]

27. Houston F, Foster JD, Chong A et al. Transmission of BSE by blood transfusion in sheep. Lancet 2000; 356 (9234): 999-1000.         [ Links ]

28. Center for Disease Control and Prevention. From the CDC. Public Health Service recommendations for the use of vaccines manufactured with bovine-derived material. JAMA 2001; 285 (5): 532.         [ Links ]

29. Pammer J, Weninger W, Tschachler E. Human keratinocytes express cellular prion-related protein in vitro and during inflammatory skin disease. Am J Pathol 1998; 153 (5): 1353-8.        [ Links ]

30. US Department of Health and Human Services. BSE fears lead to cosmetic ban. Federal Register, 2001; 66 (163): 44146-9.         [ Links ]

31. De Paepe K, Vandamme P, Roseeuw D et al. Ceramides, cholesterol, free fat acids containing cosmetics: The effect on the barrier function. SÖFW Journal, 1996; 122: 199-204.        [ Links ]

 

 

Correspondence to
Omar Lupi
Mary Moody Northern Pavilion 301 - University Blvd - Galveston/TX
Zip Code: 77555-0436, USA
Tel/Fax: +1-409-747-8145 / +1-409-747-8150
E-mail: omrosasa@utmb.edu

Received in June, 05th of 2002.
Approved by the Consultive Council and accepted for publication in July, 31st of 2002.

 

 

* Work done at the University of Texas Medical Branch (UTMB) - Sealy Center for Vaccine Development.

 

 

Questions and Answers to Questions

1. Além dos seres humanos que outros animais já foram comprovadamente infectados pelos prions?
a) suínos e ovídeos
b) ovídeos e muares
c) gado bovino e ovídeos
d) felinos e muares
e) galinhas e roedores

2. O termo "prions" pode ser melhor definido como:
a) proteínas recombinantes
b) proteínas mutagênicas
c) proteínas infecciosas
d) proteínas transgênicas
e) proteínas quiméricas

3. A base fisiopatogênica para a atuação dos prions anormais (PrPSc) se dá por:
a) serem proteínas com aminoácidos translocados
b) serem proteínas com estrutura espacial alterada
c) serem produzidos por DNA alterado por mutação
d) serem produzidos por RNA alterado por mutação
e) tanto o DNA quanto o RNA estão alterados

4. A proteína priônica aberrante (PrPSc) quando comparada à forma norma dominante (PrPC) se caracteriza por:
a) resistência às proteases
b) maior solubilidade em água
c) localização transmembrana
d) predomínio de cadeias alfa
e) não apresenta diferença significativa

5. A doença de Creutzfeldt-Jakob (CJD) foi descrita e tem sido extensivamente estudada entre:
a) aborígenes australianos
b) aborígenes da Nova Guiné
c) populações caucasianas
d) judeus ashkenasi
e) populações afro-americanas

6. A hipótese prion pode ser melhor explicada por:
a) DNA produzindo RNA mensageiro com a síntese de proteína anormal
b) RNA mensageiro codificando DNA através da transcriptase reversa
c) RNA mensageiro codificando proteína anômala por erro de transdução
d) Proteína de isoforma anormal sem participação de DNA ou RNA
e) Mutação no RNA mensageiro codifica proteína anormal que se dissemina

7. Doenças priogênicas já foram comprovadamente transmitidas a seres humanos em todas as opções abaixo, exceto:
a) transplante de dura-mater
b) transplante de córnea
c) hormônio de crescimento cadavérico
d) material cirúrgico contaminado
e) transplante cardíaco

8. Qual dos procedimentos de esterilização abaixo parece ser efetivo na descontaminação de material infectado por prions?
a) Aquecimento a 360°C por 1 hora
b) Exposição ao UVC por até 2 horas
c) Hidróxido de sódio por 1 hora seguido de autoclavagem
d) Utilização de filtros com orifícios de menos de 20 mm
e) Aplicação de óxido nítrico por 30 minutos seguido de autoclavagem

9. Entre os tecidos considerados de alto risco para a transmissão da "doença da vaca louca" podemos destacar:
a) Baço e fígado
b) Pâncreas e timo
c) Pericárdio e linfonodos
d) Olhos e cérebro
e) Colágeno e ossos

10. Produtos de origem bovina, para uso biomédico, relacionados com uma possível transmissão da infecção priogênica incluem:
a) colágeno bovino injetável
b) laticínios de origem bovina
c) vacinas para uso médico
d) implantes odontológicos
e) insulina de origem bovina

11. A epidemia de kuru na Papua Nova Guiné acometeu principalmente:
a) Homens jovens
b) Idosos e obesos
c) Mulheres e crianças
d) Imunodeprimidos
e) Gêmeos univitelinos

12. a nova variante da doença de Creutzfeldt-Jakob (nvCJD) quando comparada à CJD:
a) tem evolução clínica mais lenta
b) a taxa de letalidade é maior
c) afeta uma faixa etária mais jovem
d) apresenta distribuição também randômica
e) não apresenta diferenças detectáveis

13. Sobre a proteína priônica do estado dominante (PrPC) podemos afirmar:
a) É uma proteína de localização citoplasmática
b) O gene codificador está localizado no cromossomo 20
c) É uma proteína filtrável de 12 Kilodaltons
d) É uma proteína não-filtrável de configuração dextrógera
e) É uma glicoproteína de alto peso molecular

14. A pele, por expressar a proteína priônica celular, é um alvo para as doençãs priogênicas. A disseminação da moléstia se dá:
a) pelos axônios e neurônios
b) pelas hemácias e plaquetas
c) pelos linfócitos e macrófagos
d) através dos vasos linfáticos
e) por neurotransmissores cutâneos

15. O scrapie é uma doença priogênica que afeta:
a) gado bovino
b) suínos
c) ovinos
d) celenterados
e) insetos

16. a disseminação da "doença da vaca louca" ou encefalopatia espongiosiforme bovina deve-se a:
a) contaminação dos pastos pelos prions
b) transmissão dos prions por vacinas contaminadas
c) transmissão por aerossol entre os animais no pasto
d) transmissão através de alimentos contaminados
e) a forma de transmissão nunca foi totalmente elucidada

17. O substrato anatomopatológico das doenças priogênicas é:
a) hepatite crônica ativa
b) encefalopatia espongiosiforme
c) pneumonite obstrutiva crônica
d) miocardite amiotrófica grave
e) vasculite sem leucocitoclasia

18. Qual dos padrões epidemiológicos melhor caracteriza as doenças priogênicas:
a) alta incidência
b) alta prevalência
c) alta letalidade
d) moderada morbidade
e) alta transcendência

19. É exemplo de doença priogênica em seres humanos:
a) doença de Alzheimer
b) esclerose lateral amiotrófica
c) Sd. da Insônia familiar fatal
d) Paralisia geral progressiva
e) Esclerose múltipla

20. As ceramidas de uso tópico são substâncias de risco potencial para a transmissão das doenças priogênicas por diversos fatores, exceto:
a) atuam na pele, órgão que expressa a proteína priônica
b) têm como origem os cerebrosídeos, tecido com alta expressão priônica
c) podem ter como origem o gado bovino contaminado por prions
d) podem sofrer contaminação durante o processo de fabricação
e) são de difícil esterilização para prions pois perderiam sua capacidade biológica

GABARITO
Nevo Melanocítico Congênito
2002; 77(6): 649-656

1 - c
2 - a
3 - d
4 - c
5 - c
6 - b
7 - e
8 - c
9 - e
10 - e

11 - b
12 - c
13 - b
14 - e
15 - a
16 - a
17 - c
18 - a
19 - d
20 - e