Amyloidosis refers to a group of protein misfolding diseases characterized by deposition of a particular amyloid protein in various organs and tissues of animals and humans. Various types and clinical forms of amyloidosis, in which the pathology and pathogenesis is diverse depending upon the underlying causes and species affected, are reported in domestic and wild animals. The clinical findings are also quite variable consequent to the variation of the tissues and organs involved and the extent of functional disruption of the affected organs in various animal species. The affected organs may be enlarged and exhibit variable pallor grossly, or the amyloid deposit may be discernible only after microscopic examination of the affected tissues. Amyloid appears as a pale eosinophilic homogenous extracellular deposit in tissues. However, microscopic examination and Congo red staining with green birefringence under polarized light are needed to confirm amyloid and differentiate it from other apparently similar extracellular deposits such as collagen and fibrin. Identifying the type of amyloid deposit needs immunohistochemical staining, ultrastructural characterization of the amyloid fibril, and if feasible also genetic studies of the involved species for clinical and prognostic purposes. This paper provides a concise review of the occurrence of amyloidosis in domestic and wild animals. 1. Introduction Amyloid is a pathologic proteinaceous substance deposited between cells in various tissues and organs of the body in a wide variety of clinical settings [1]. Although there are other components present in the deposit, the amyloid protein fibril is the main component of the amyloid substance. The deposit differs in protein composition depending upon the types of amyloidosis and the different clinical forms. Each clinical entity of amyloidosis may be manifested by a distinct clinical form with chemically specific amyloid fibril protein. This indicates that amyloid is a biochemically heterogeneous substance, although there are similarities in properties and staining characteristics. 1.1. Nomenclature and Classification of Amyloidosis According to the WHO-IUIS Nomenclature Subcommittee [2] on the nomenclature of amyloid and amyloidosis, amyloid and amyloidosis are classified based on the amyloid fibril protein, followed by a designation of the fibril protein precursor. The capital letter A for amyloid is followed by the protein designation in abbreviated form. For example AL-amyloid refers to the amyloid derived from immunoglobulin light chain and may be seen in
References
[1]
A. Abbas, “Diseases of immunity: amyloidosis,” in Pathologic Basis of Disease, V. Kumar, A. K. Abbas, and N. Fausto, Eds., pp. 258–264, Elsevier Saunders, Philadelphia, Pa, USA, 7th edition, 2005.
[2]
WHO-IUIS, Nomenclature Sub-Committee, “Nomenclature of amyloid and amyloidosis,” Bulletin of the World Health Organization, vol. 71, no. 1, pp. 105–112, 1993.
[3]
M. A. Gertz, “The classification and typing of amyloid deposits,” American Journal of Clinical Pathology, vol. 121, no. 6, pp. 787–789, 2004.
[4]
C. L. Murphy, M. Eulitz, R. Hrncic et al., “Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens,” American Journal of Clinical Pathology, vol. 116, no. 1, pp. 135–142, 2001.
[5]
E. Gruys, “Protein folding pathology in domestic animals,” Journal of Zhejiang University, vol. 5, no. 10, pp. 1226–1238, 2004.
[6]
C. Ménsua, L. Carrasco, M. J. Bautista et al., “Pathology of AA amyloidosis in domestic sheep and goats,” Veterinary Pathology, vol. 40, no. 1, pp. 71–80, 2003.
[7]
P. Westermark, “The pathogenesis of amyloidosis: understanding general principles,” The American Journal of Pathology, vol. 152, no. 5, pp. 1125–1127, 1998.
[8]
R. H. Falk, R. l. Comenzo, and M. Skinner, “The systemic amyloidosis, medical progress, a review article,” The New England Journal of Medicine, vol. 337, no. 13, pp. 898–909, 1997.
[9]
M. F. Khan and R. H. Falk, “Amyloidosis,” Postgraduate Medical Journal, vol. 77, pp. 686–693, 2001.
[10]
N. Upragarin, W. J. M. Landman, W. Gaastra, and E. Gruys, “Extrahepatic production of acute phase serum amyloid A,” Histology and Histopathology, vol. 20, no. 4, pp. 1295–1307, 2005.
[11]
G. Ramadori, J. D. Sipe, and H. R. Colten, “Expression and regulation of the murine serum amyloid A (SAA) gene in extrahepatic sites,” Journal of Immunology, vol. 135, no. 6, pp. 3645–3647, 1985.
[12]
J. T. Guo, J. Yu, D. Grass, F. C. De Beer, and M. S. Kindy, “Inflammation-dependent cerebral deposition of serum amyloid A protein in a mouse model of amyloidosis,” Journal of Neuroscience, vol. 22, no. 14, pp. 5900–5909, 2002.
[13]
W. J. M. Landman, A. E. J. M. V. D. Bogaard, P. Doornenbal, P. C. J. Tooten, A. R. W. Eibers, and E. Gruys, “The role of various agents in chicken amyloid arthropathy,” Amyloid, vol. 5, no. 4, pp. 266–278, 1998.
[14]
K. Lundmark, G. T. Westermark, S. Nystr？m, C. L. Murphy, A. Solomon, and P. Westermark, “Transmissibility of systemic amyloidosis by a prion-like mechanism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 10, pp. 6979–6984, 2002.
[15]
G. Bhak, Y. J. Choe, and S. R. Paik, “Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation,” BMB Reports, vol. 42, no. 9, pp. 541–551, 2009.
[16]
P. W. Snyder, “Diseases of immunity: amyloidosis,” in Pathologic Basis of Veterinary Diseases, M. D. McGavin and J. F. Zachary, Eds., pp. 246–251, Mosby Elsevier, St Lois, Mo, USA, 2007.
[17]
D. Y. Kim, H. W. Taylor, S. C. Eades, and D. Y. Cho, “Systemic AL amyloidosis associated with multiple myeloma in a horse,” Veterinary Pathology, vol. 42, no. 1, pp. 81–84, 2005.
[18]
R. Kisilevsky, “Heparan sulfate proteoglycans in amyloidogenesis: an epiphenomenon, a unique factor, or the tip of a more fundamental process?” Laboratory Investigation, vol. 63, no. 5, pp. 589–591, 1990.
[19]
R. Badolato, J. M. Wang, W. J. Murphy et al., “Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes,” Journal of Experimental Medicine, vol. 180, no. 1, pp. 203–209, 1994.
[20]
K. H. Johnson, P. Westermark, K. Sletten, and T. D. O'Brien, “Amyloid proteins and amyloidosis in domestic animals,” Amyloid, vol. 3, no. 4, pp. 270–289, 1996.
[21]
K. A. Terio, T. O'Brien, N. Lamberski, T. R. Famula, and L. Munson, “Amyloidosis in black-footed cats (Felis nigvipes),” Veterinary Pathology, vol. 45, no. 3, pp. 393–400, 2008.
[22]
J. T. Guo, C. E. Aldrich, W. S. Mason, and J. C. Pugh, “Characterization of serum amyloid A protein mRNA expression and secondary amyloidosis in the domestic duck,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14548–14553, 1996.
[23]
S. P. DiBartola, M. J. Tarr, D. M. Webb, and U. Giger, “Familial renal amyloidosis in Chinese Shar Pei dogs,” Journal of the American Veterinary Medical Association, vol. 197, no. 4, pp. 483–487, 1990.
[24]
W. Jakob, “Spontaneous amyloidosis of mammals,” Veterinary Pathology, vol. 8, no. 4, pp. 292–306, 1971.
[25]
R. Johnson and K. Jamison, “Amyloidosis in six dairy cows,” Journal of the American Veterinary Medical Association, vol. 185, no. 12, pp. 1538–1543, 1984.
[26]
D. W. Hayden, K. H. Johnson, C. B. Wolf, and P. Westermark, “AA Amyloid-associated gastroenteropathy in a horse,” Journal of Comparative Pathology, vol. 98, no. 2, pp. 195–204, 1988.
[27]
W. Zschiesche and W. Jakob, “Pathology of animal amyloidoses,” Pharmacology and Therapeutics, vol. 41, no. 1-2, pp. 49–83, 1989.
[28]
A. S. Blunden and K. C. Smith, “Generalised amyloidosis and acute liver haemorrhage in four cats,” Journal of Small Animal Practice, vol. 33, pp. 566–570, 1992.
[29]
H. A. Seifi, K. Karimi, and A. R. Movasseghi, “Renal amyloidosis in cattle: a case report in Iran,” Journal of Veterinary Medicine, Series B, vol. 44, no. 10, pp. 631–633, 1997.
[30]
W. J. M. Landman, “Amyloid arthropathy in chickens,” Veterinary Quarterly, vol. 21, no. 3, pp. 78–82, 1999.
[31]
W. J. Hadlow and W. L. Jellison, “Amyloidosis in Rocky Mountain bighorn sheep,” Journal of the American Veterinary Medical Association, vol. 141, pp. 243–247, 1962.
[32]
A. Sato, T. Koga, M. Inoue, and N. Goto, “Pathological observations of amyloidosis in swans and other Anatidae,” The Japanese Journal of Veterinary Science, vol. 43, no. 4, pp. 509–519, 1981.
[33]
R. S. Kingston, M. S. Shih, and S. P. Snyder, “Secondary amyloidosis in Dall's sheep,” Journal of wildlife diseases, vol. 18, no. 3, pp. 381–383, 1982.
[34]
R. P. Linke, P. R. Hol, and O. Geisel, “Immunohistochemical identification of generalized AA-amyloidosis in a mountain gazelle (Gazella gazella),” Veterinary pathology, vol. 23, no. 1, pp. 63–67, 1986.
[35]
B. A. Rideout, R. J. Montali, R. S. Wallace et al., “Renal medullary amyloidosis in Dorcas gazelles,” Veterinary Pathology, vol. 26, no. 2, pp. 129–135, 1989.
[36]
L. Munson, “Diseases of captive cheetahs (Acinonyx jubatus): results of the Cheetah Research Council pathology survey, 1989–1992,” Zoo Biology, vol. 12, pp. 105–124, 1993.
[37]
J. M. Nieto, S. Vázquez, M. I. Quiroga, M. López-Pe？a, F. Guerrero, and E. Gruys, “Spontaneous AA-amyloidosis in mink (Mustela vison). Description of eight cases, one of which exhibited intracellular amyloid deposits in lymph node macrophages,” European Journal of Veterinary Pathology, vol. 1, pp. 99–103, 1995.
[38]
R. E. Papendick, L. Munson, T. D. O'Brien, and K. H. Johnson, “Systemic AA amyloidosis in captive cheetahs (Acinonyx jubatus),” Veterinary Pathology, vol. 34, no. 6, pp. 549–556, 1997.
[39]
C. Schulze, M. Brügmann, M. B？er, H. P. Brandt, J. Pohlenz, and R. P. Linke, “Generalized AA-amyloidosis in Siberian Tigers (Panthera tigris altaica) with predominant renal medullary amyloid deposition,” Veterinary Pathology, vol. 35, no. 1, pp. 70–74, 1998.
[40]
J. H. Williams, E. Van Wilpe, and M. Momberg, “Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo),” Journal of the South African Veterinary Association, vol. 76, no. 2, pp. 90–98, 2005.
[41]
M. M. Garner, J. T. Raymond, T. D. O'Brien, R. W. Nordhausen, and W. C. Russell, “Amyloidosis in the black-footed ferret (Mustela nigripes),” Journal of Zoo and Wildlife Medicine, vol. 38, no. 1, pp. 32–41, 2007.
[42]
J. T. Boyce, S. P. DiBartola, D. J. Chew, and P. W. Gasper, “Familial renal amyloidosis in Abyssinian cats,” Veterinary Pathology, vol. 21, no. 1, pp. 33–38, 1984.
[43]
S. P. DiBartola and M. J. tarr, “Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis,” Journal of Comparative Pathology, vol. 96, no. 4, pp. 387–398, 1986.
[44]
T. A. Niewold, J. S. Van Der Linde-Sipman, C. Murphy, P. C. J. Tooten, and E. Gruys, “Familial amyloidosis in cats: Siamese and Abyssinian aa proteins differ in primary sequence and pattern of deposition,” Amyloid, vol. 6, no. 3, pp. 205–209, 1999.
[45]
W. A. Gonnerman, R. Elliott-Bryant, I. Carreras, J. D. Sipe, and E. S. Cathcart, “Linkage of protection against amyloid fibril formation in the mouse to a single, autosomal dominant gene,” Journal of Experimental Medicine, vol. 181, no. 6, pp. 2249–2252, 1995.
[46]
J. S. Liang, R. Elliott-Bryant, T. Hajri, J. D. Sipe, and E. S. Cathcart, “A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice,” Biochimica et Biophysica Acta, vol. 1394, no. 1, pp. 121–126, 1998.
[47]
Y. Ren, S. A. G. Reddy, and W. S. L. Liao, “Purification and identification of a tissue-specific repressor involved in serum amyloid A1 gene expression,” Journal of Biological Chemistry, vol. 274, no. 52, pp. 37154–37160, 1999.
[48]
J. Yu, J.-T. Guo, H. Zhu, and M. S. Kindy, “Amyloid formation in the rat: adenoviral expression of mouse serum amyloid A proteins,” Amyloid, vol. 7, no. 1, pp. 32–40, 2000.
[49]
J. H. Ovelg？nne, W. J. M. Landman, E. Gruys, A. L. J. Gielkens, and B. P. H. Peeters, “Identical amyloid precursor proteins in two breeds of chickens which differ in susceptibility to develop amyloid arthropathy,” Amyloid, vol. 8, no. 1, pp. 41–51, 2001.
[50]
T. B. Hawthorne, B. Bolon, and D. J. Meyer, “Systemic amyloidosis in a mare,” Journal of the American Veterinary Medical Association, vol. 196, no. 2, pp. 323–325, 1990.
[51]
H. Taniyama, S. Yamamoto, T. Sako, K. Hirayama, H. Higuchi, and H. Nagahata, “Systemic κAL amyloidosis associated with bovine leukocyte adhesion deficiency,” Veterinary Pathology, vol. 37, no. 1, pp. 98–100, 2000.
[52]
P. Labelle, M. E. Roy, and F. C. Mohr, “Primary diffuse tracheobronchial amyloidosis in a dog,” Journal of Comparative Pathology, vol. 131, no. 4, pp. 338–340, 2004.
[53]
M. F. Besancon, B. A. Stacy, A. E. Kyles et al., “Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog,” Journal of the American Veterinary Medical Association, vol. 224, no. 8, pp. 1302–1280, 2004.
[54]
R. P. Linke, O. Geisel, and K. Mann, “Equine cutaneous amyloidosis derived from an immunoglobulin lambda-light chain. Immunohistochemical, immunochemical and chemical results,” Biological Chemistry Hoppe-Seyler, vol. 372, no. 9, pp. 835–843, 1991.
[55]
E. R. Burrough, R. K. Myers, J. Hostetter, et al., “Amyloid deposition in 2 feline thymomas,” Veterinary Pathology. In press.
[56]
S. J. Platz, W. Breuer, O. Geisel, R. P. Linke, and W. Hermanns, “Identification of λ light chain amyloid in eight canine and two feline extramedullary plasmacytomas,” Journal of Comparative Pathology, vol. 116, no. 1, pp. 45–54, 1997.
[57]
M. M. Picken, “The changing concepts of amyloid,” Archives of Pathology and Laboratory Medicine, vol. 125, no. 1, pp. 38–43, 2001.
[58]
G. Merlini and M. J. Stone, “Dangerous small B-cell clones,” Blood, vol. 108, no. 8, pp. 2520–2530, 2006.
[59]
S. B. Prusiner, M. P. McKinley, and K. A. Bowman, “Scrapie prions aggregate to form amyloid-like birefringent rods,” Cell, vol. 35, no. 2, pp. 349–358, 1983.
[60]
T. D. O'Brien, J. D. Wagner, K. N. Litwak et al., “Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus,” Veterinary Pathology, vol. 33, no. 5, pp. 479–485, 1996.
[61]
M. Hoenig, G. Hall, D. Ferguson et al., “A feline model of experimentally induced islet amyloidosis,” American Journal of Pathology, vol. 157, no. 6, pp. 2143–2150, 2000.
[62]
J. M. Gliatto and J. Alroy, “Cutaneous amyloidosis in a horse with lymphoma,” The Veterinary Record, vol. 137, no. 3, pp. 68–69, 1995.
[63]
R. P. Linke, O. Geisel, and K. Mann, “Equine cutaneous amyloidosis derived from an immunoglobulin lambda-light chain. Immunohistochemical, immunochemical and chemical results,” Biological Chemistry Hoppe-Seyler, vol. 372, no. 9, pp. 835–843, 1991.
[64]
S. V. Abdelkader, R. Gudding, and K. Nordstoga, “Clinical chemical constituents in relation to liver amyloidosis in serum-producing horses,” Journal of Comparative Pathology, vol. 105, no. 2, pp. 203–211, 1991.
[65]
M. Woldemeskel, “Primary localized nodular cutaneous amyloidosis in a male neutered Golden Retriever,” Deutsche Tierarztliche Wochenschrift, vol. 114, no. 12, pp. 473–475, 2007.
[66]
T. L. Gross, P. J. Ihrke, and E. J. Walder, “Veterinary dermatopathology: a macroscopic and microscopic evaluation of canine and feline skin diseases,” Mosby Year Book Inc. St Louis, Mo, USA, pp. 229–232, 1992.
[67]
D. W. Scott, W. H. Miller, and C. E. Graffin, Muller & Kirk’s Small Animal Dermathology, Saunders, 6th edition, 2001.
[68]
P. H. Rowland, B. A. Valentine, K. E. Stebbins, and C. A. Smith, “Cutaneous plasmacytomas with amyloid in six dogs,” Veterinary Pathology, vol. 28, no. 2, pp. 125–130, 1991.
[69]
J. A. Yager and D. W. Scott, “The skin and its appendages,” in Pathology of Domestic Animals, K. V. F. Jubb, P. C. Kennedy, and N. Palmer, Eds., vol. 1, p. 628, Academic Press, San Diego, Calif, USA, 4th edition, 1993.
[70]
D. Borràs, I. Ferrer, M. Pumarola, and B. Murcia, “Age-related changes in the brain of the dog,” Veterinary Pathology, vol. 36, no. 3, pp. 202–211, 1999.
[71]
E. Gruys, “First workshop and clinic on neuropathology in geriatric dogs and cats. Wiesbaden, Germany, May 4-5, 1995,” Amyloid, vol. 2, no. 4, pp. 280–283, 1995.
[72]
N. Papaioannou, P. C. J. Tooten, A. M. Van Ederen et al., “Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques,” Amyloid, vol. 8, no. 1, pp. 11–21, 2001.
[73]
J. E. Rofina, N. Papaioannou, I. van Andel, et al., “Cerebrovascular amyloidosis may cause a decrease of blood supply leading to oxidative damage and formation of amyloid plaques in the aged canine brain,” in Amyloid and Amyloidosis, M. Bely and A. Apathy, Eds., vol. 9, pp. 445–447, Apathy, Budapest, Hungary, 2001.
[74]
J. E. Rofina, I. van Andel, A. M. van Andel, N. Papaioannou, H. Yamaguchi, and E. Gruys, “Canine counterpart of senile plaques near capillaries but lack of spatial relationship with activated microglia and macrophages,” Amyloid Journal of Protein Folding Disorders, vol. 10, pp. 86–96, 2003.
[75]
M. A. Mena, J. A. Rodríguez-Navarro, and J. G. De Yébenes, “The multiple mechanisms of amyloid deposition: the role of parkin,” Prion, vol. 3, no. 1, pp. 5–11, 2009.
[76]
R. Schr？der and R. P. Linke, “Cerebrovascular involvement in systemic AA and AL amyloidosis: a clear haematogenic pattern,” Virchows Archiv, vol. 434, no. 6, pp. 551–560, 1999.
[77]
H. Keiichi, X. Fu, P. Zhang, et al., “Mouse model to study systemic amyloidosis: is Prion-like transmission a common pathogenic mechanism?” in Amyloidosis, Mechanisms and Prospect for Therapy, S. Sarantseva, Ed., pp. 164–180, Intech publishers, Rijeka, Croatia, 2011.
[78]
E. Gruys, “Amyloidosis in the bovine kidney,” Veterinary Science Communications, vol. 1, no. 1, pp. 265–276, 1977.
[79]
G. Maxie and S. J. Newman, “Urinary system,” in Pathology of Domestic Animals, K. V. F. Jubb, P. C. Kennedy, and N. Palmer, Eds., vol. 2, pp. 463–465, Academic Press, San Diego, Calif, USA, 7th edition, 2007.
[80]
E. Biescas, W. Jirón, S. Climent et al., “AA amyloidosis induced in sheep principally affects the gastrointestinal tract,” Journal of Comparative Pathology, vol. 140, no. 4, pp. 238–246, 2009.
[81]
M. D. Krista, La Perle, and M. D. Capen, “Endocrine system,” in Pathologic Basis of Veterinary Diseases, M. D. McGavin and J. F. Zachary, Eds., pp. 734–736, Mosby Elsevier, St Lois, Mo, USA, 2007.
[82]
J. R. Wright, E. Calkins, and R. L. Humphrey, “Potassium permanganate reaction in amyloidosis. A histologic method to assist in differentiating forms of this disease,” Laboratory Investigation, vol. 36, no. 3, pp. 274–281, 1977.
[83]
S. Shtrasburg, R. Gal, E. Gruys et al., “An ancillary tool for the diagnosis of amyloid a amyloidosis in a variety of domestic and wild animals,” Veterinary Pathology, vol. 42, no. 2, pp. 132–139, 2005.
[84]
O. Lupi and M. A. Peryassu, “An emerging concept of prion infections as a form of transmissible cerebral amyloidosis,” Prion, vol. 1, no. 4, pp. 223–227, 2007.
[85]
J. Savistchenko, Z. E. Arellano-Anaya, O. Andréoletti, and D. Vilette, “Mammalian prions: tracking the infectious entities,” Prion, vol. 5, no. 2, pp. 84–87, 2011.
[86]
M. Imran and S. Mahmood, “An overview of animal prion diseases,” Virology Journal, vol. 8, article 493, 2011.
[87]
C. Ligios, M. G. Cancedda, A. Carta et al., “Sheep with scrapie and mastitis transmit infectious prions through the milk,” Journal of Virology, vol. 85, no. 2, pp. 1136–1139, 2011.
[88]
The Merck Veterinary Manual, “Amyloidosis,” http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/100200.htm&word.
[89]
P. Brown, R. Meyer, F. Cardone, and M. Pocchiari, “Ultra-high-pressure inactivation of prion infectivity in processed meat: a practical method to prevent human infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 6093–6097, 2003.
[90]
R. Morales, K. A. Buytaert-Hoefen, D. Gonzalez-Romero et al., “Reduction of prion infectivity in packed red blood cells,” Biochemical and Biophysical Research Communications, vol. 377, no. 2, pp. 373–378, 2008.
[91]
P. Tourlomoussis, P. D. Eckersall, M. M. Waterson, and S. Buncic, “A comparison of acute phase protein measurements and meat inspection findings in cattle,” Foodborne Pathogens and Disease, vol. 1, no. 4, pp. 281–290, 2004.
[92]
T. Yoshida, T. Nomura, N. Shinoda, T. Kusama, K. I. Kadowaki, and K. Sugiura, “Development of PCR primers for the detection of porcine DNA in feed using mtATP6 as the target sequence,” Journal of the Food Hygienic Society of Japan, vol. 50, no. 2, pp. 89–92, 2009.
