• 1. Mann PJ, Tennenbaum M, Quastel JH. Acetylcholine metabolism in the central nervous system. Biochem J 1939; 33: 15061518.

  • 2. Paparrigopoulos T, Tzavellas E, Karaiskos D, et al. Complete recovery from undertreated Wernicke-Korsakoff syndrome following aggressive thiamine treatment. In Vivo 2010; 24: 231233.

    • Search Google Scholar
    • Export Citation
  • 3. Weise Prinzo Z, de Benoist B. Meeting the challenges of micronutrient deficiencies in emergency-affected populations. Proc Nutr Soc 2002; 61: 251257.

    • Search Google Scholar
    • Export Citation
  • 4. Baggs RB, DeLahunta A, Averill DR. Thiamine deficiency encephalopathy in a specific-pathogen-free cat colony. Lab Anim Sci 1978; 28: 323326.

    • Search Google Scholar
    • Export Citation
  • 5. Barnerias C, Saudubray JM, Touati G, et al. Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Dev Med Child Neurol 2010; 52:e1e9.

    • Search Google Scholar
    • Export Citation
  • 6. Rachid MA, Filho EF, Carvalho AU, et al. Polioencephalomalacia in cattle. Asian J Anim Vet Adv 2011; 6: 126131.

  • 7. Wohlsein P, Peters M, Geburek F, et al. Polioencephalomalacia in captive harbour seals (Phoca vitulina). J Vet Med A Physiol Pathol Clin Med 2003; 50: 145150.

    • Search Google Scholar
    • Export Citation
  • 8. Heller S, Salkeld RM, Korner WF. Vitamin B1 status in pregnancy. Am J Clin Nutr 1974; 27: 12211224.

  • 9. Lindboe CF, Loberg EM. Wernicke's encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989; 90: 125129.

  • 10. Seehra H, MacDermott N, Lascelles RG, et al. Wernicke's encephalopathy after vertical banded gastroplasty for morbid obesity. BMJ 1996; 312:434.

    • Search Google Scholar
    • Export Citation
  • 11. Anglesea JD, Jackson AJ. Thiaminase activity in fish silage and moist fish feed. Anim Feed Sci Technol 1985; 13: 3946.

  • 12. Lienhard GE. Kinetic evidence for a 4 amino-2-methyl-5 pyrimidinyl methyl enzyme intermediate in the Thiaminase I reaction. Biochemistry 1970; 9: 30113020.

    • Search Google Scholar
    • Export Citation
  • 13. Nielands JB. Thiaminase in aquatic animals of Nova Scotia. J Fish Res Board Can 1947; 7: 9499.

  • 14. Brown SB, Fitzsimons JD, Honeyfield DC, et al. Implications of thiamine deficiency in Great Lakes salmonines. J Aquat Anim Health 2005; 17: 113124.

    • Search Google Scholar
    • Export Citation
  • 15. Myers BJ. The rearing of a grey seal in captivity. Can Field Nat 1955; 69: 151153.

  • 16. Rigdon RH, Drager GA. Thiamine deficiency in sea lions (Otaria californiana) fed only frozen fish. J Am Vet Med Assoc 1955; 127: 453455.

    • Search Google Scholar
    • Export Citation
  • 17. White JR. Thiamine deficiency in an Atlantic bottle-nosed dolphin (Tursiops truncatus) on a diet of raw fish. J Am Vet Med Assoc 1970; 157: 559562.

    • Search Google Scholar
    • Export Citation
  • 18. Geraci JR. Experimental thiamine deficiency in captive harp seals, Phoca groenlandica, induced by eating herring, Clupea harengus, and smelts, Osmerus mordax. Can J Zool 1972; 50: 179195.

    • Search Google Scholar
    • Export Citation
  • 19. Geraci JR. Thiamine deficiency in seals and recommendations for its prevention. J Am Vet Med Assoc 1974; 165: 801803.

  • 20. Geraci JR. Dietary disorders in marine mammals: synthesis and new findings. J Am Vet Med Assoc 1981; 179: 11831191.

  • 21. Bethke G, Changbumrung S, Feldheim W. Micromethod for the determination of erythrocyte transketolase activity. Int J Vitam Nutr Res 1973; 43: 426437.

    • Search Google Scholar
    • Export Citation
  • 22. Liu CS, Tsai CS, Kuo CL, et al. Oxidative stress-related alteration of the copy number of mitochondrial DNA in human leukocytes. Free Radic Res 2003; 37: 13071317.

    • Search Google Scholar
    • Export Citation
  • 23. De La Haba G, Leder IG, Racker E. Crystalline transketolase from bakers' yeast: isolation and properties. J Biol Chem 1955; 214: 409426.

    • Search Google Scholar
    • Export Citation
  • 24. Smeets EH, Muller H, de Wael J. A NADH-dependent transketolase assay in erythrocyte hemolysates. Clin Chim Acta 1971; 33: 379386.

  • 25. Hinman LM, Blass JP. An NADH-linked spectrophotometric assay for pyruvate dehydrogenase complex in crude tissue homogenates. J Biol Chem 1981; 256: 65836586.

    • Search Google Scholar
    • Export Citation
  • 26. Schwab MA, Kölker S, van den Heuvel LP, et al. Optimized spectrophotometric assay for the completely activated pyruvate dehydrogenase complex in fibroblasts. Clin Chem 2005; 51: 151160.

    • Search Google Scholar
    • Export Citation
  • 27. Passonneau JV, Lowry OH. Biological methods: enzymatic analysis: a practical guide. New York: Humana Press, 1993; 910.

  • 28. Morey AV, Juni E. Resolution, reconstitution, and other methods for the study of binding of thiamine pyrophosphate to enzymes. In: Donald BM, Lemuel DW, eds. Methods in enzymology. Waltham, Mass: Academic Press, 1970; 238245.

    • Search Google Scholar
    • Export Citation
  • 29. Zajicek JL, Tillitt DE, Honeyfield DC, et al. Method for measuring total thiaminase activity in fish tissues. J Aquat Anim Health 2005; 17: 8294.

    • Search Google Scholar
    • Export Citation
  • 30. Honeyfield DC, Hanes JW, Brown L, et al. Comparison of thiaminase activity in fish using the radiometric and 4-nitrothiophenol colorimetric methods. J Great Lakes Res 2010; 36: 641645.

    • Search Google Scholar
    • Export Citation
  • 31. Morris JA, Gardner MJ. Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates. Br Med J (Clin Res Ed) 1988; 296: 13131316.

    • Search Google Scholar
    • Export Citation
  • 32. de Sant'Ana FJF, Lemos RAA, Nogueira APA, et al. Polioencephalomalacia in ruminants. Pesqui Vet Bras 2009; 29: 681694.

  • 33. Wobeser G, Daoust PY, Hunt HM. Polioencephalomalacia-like disease in pronghorns (Antilocapra americana). J Wildl Dis 1983; 19: 248252.

    • Search Google Scholar
    • Export Citation
  • 34. Olkowski AA, Gooneratne SR, Rousseaux CG, et al. Role of thiamine status in sulphur induced polioencephalomalacia in sheep. Res Vet Sci 1992; 52: 7885.

    • Search Google Scholar
    • Export Citation
  • 35. Trebukhina RV, Ostrovsky YM, Petushok VG, et al. Effect of thiamine deprivation on thiamine metabolism in mice. J Nutr 1981; 111: 505513.

    • Search Google Scholar
    • Export Citation
  • 36. Rooprai HK, Pratt OE, Shaw GK, et al. Thiamine pyrophosphate effect and normalized erythrocyte transketolase activity ratio in Wernicke-Korsakoff patients and acute alcoholics undergoing detoxification. Alcohol Alcohol 1996; 31: 493501.

    • Search Google Scholar
    • Export Citation
  • 37. Trebukhina RV, Ostrovsky YM, Mikhaltsevich GN, et al. Transketolase, pyruvate and oxoglutarate dehydrogenase activities and [14C]thiamin turnover in tissues of mice fed thiamin-deficient diet. J Nutr 1983; 113: 12851291.

    • Search Google Scholar
    • Export Citation
  • 38. Bonjour JP. Vitamins and alcoholism. IV. Thiamin. Int J Vitam Nutr Res 1980; 50: 321338.

  • 39. Alexander-Kaufman K, Harper C. Transketolase: observations in alcohol-related brain damage research. Int J Biochem Cell Biol 2009; 41: 717720.

    • Search Google Scholar
    • Export Citation
  • 40. Leukocyte transketolase activity: an indicator of thiamin nutriture. Nutr Rev 1977; 35: 185187.

  • 41. Jeyasingham MD, Pratt OE, Thomson AD, et al. Reduced stability of rat brain transketolase after conversion to the apo form. J Neurochem 1986; 47: 278281.

    • Search Google Scholar
    • Export Citation
  • 42. Okada HM, Chihaya Y, Matsukawa K. Thiamine deficiency encephalopathy in foxes and mink. Vet Pathol 1987; 24: 180182.

  • 43. A. Metabolic and structural role of thiamine in nervous tissues. Cell Mol Neurobiol 2008; 28: 923931.

  • 44. Bettendorff L, Wirtzfeld B, Makarchikov AF, et al. Discovery of a natural thiamine adenine nucleotide. Nat Chem Biol 2007; 3: 211212.

    • Search Google Scholar
    • Export Citation
  • 45. Frédérich M, Delvaux D, Gigliobianco T, et al. Thiaminylated adenine nucleotides. Chemical synthesis, structural characterization and natural occurrence. FEBS J 2009; 276: 32563268.

    • Search Google Scholar
    • Export Citation
  • 46. Greenwood J, Love ER, Pratt OE. Kinetics of thiamine transport across the blood-brain barrier in the rat. J Physiol 1982; 327: 95103.

    • Search Google Scholar
    • Export Citation
  • 47. Rindi G, Patrini C, Comincioli V, et al. Thiamine content and turnover rates of some rat nervous regions, using labeled thiamine as a tracer. Brain Res 1980; 181: 369380.

    • Search Google Scholar
    • Export Citation
  • 48. Moraes CT. What regulates mitochondrial DNA copy number in animal cells? Trends Genet 2001; 17: 199205.

  • 49. Bai RK, Perng CL, Hsu CH, et al. Quantitative PCR analysis of mitochondrial DNA content in patients with mitochondrial disease. Ann N Y Acad Sci 2004; 1011: 304309.

    • Search Google Scholar
    • Export Citation
  • 50. Ros M, Lobato MF, Garcia-Ruiz JP, et al. Integration of lipid metabolism in the mammary gland and adipose tissue by prolactin during lactation. Mol Cell Biochem 1990; 93: 185194.

    • Search Google Scholar
    • Export Citation
  • 51. Butterworth RF. Maternal thiamine deficiency: still a problem in some world communities. Am J Clin Nutr 2001; 74: 712713.

  • 52. Ortega RM, Martinez RM, Andres P, et al. Thiamin status during the third trimester of pregnancy and its influence on thiamin concentrations in transition and mature breast milk. Br J Nutr 2004; 92: 129135.

    • Search Google Scholar
    • Export Citation
  • 53. Fournier H, Butterworth RF. Effects of thiamine deficiency on thiamine-dependent enzymes in regions of the brain of pregnant rats and their offspring. Metab Brain Dis 1990; 5: 7784.

    • Search Google Scholar
    • Export Citation
  • 54. Hilker DM, Peter OF. Anti-thiamine activity in Hawaii fish. J Nutr 1966; 89: 419421.

  • 55. Yudkin WH. Thiaminase, the Chastek-paralysis factor. Physiol Rev 1949; 29: 389402.

  • 56. Ishihara T, Kinari H, Yasuda M. Studies on thiaminase I in marine fish part 2: distribution of thiaminase in marine fish. Bull Jpn Soc Sci Fish 1973; 39: 5559.

    • Search Google Scholar
    • Export Citation
  • 57. Deutsch HF, Hasler AD. Distribution of a vitamin B1 destructive enzyme in fish. Proc Soc Exp Biol Med 1943; 53: 6365.

  • 58. Ji YQ, Adelman IR. Thiaminase activity in alewives and smelt in Lakes Huron, Michigan, and Superior, in Proceedings. 21st Am Fish Soc Symp 1998; 154159.

    • Search Google Scholar
    • Export Citation
  • 59. Deutsch HF, Ott GL. Mechanism of vitamin B destruction by a factor in raw smelt. Proc Soc Exp Biol Med 1942; 51: 119122.

  • 60. Geraci JR. Diet-induced thiamine deficiency in captive marine mammals, in Proceedings. 2nd Symp Dis Husb Aquat Mamm 1969; 137144.

    • Search Google Scholar
    • Export Citation
  • 61. Langlais PJ, Mair RG, Anderson CD, et al. Long-lasting changes in regional brain amino acids and monoamines in recovered pyrithiamine treated rats. Neurochem Res 1988; 13: 11991206.

    • Search Google Scholar
    • Export Citation
  • 62. Le Roch K, Riche D, Sara SJ. Persistence of habituation deficits after neurological recovery from severe thiamine deprivation. Behav Brain Res 1987; 26: 3746.

    • Search Google Scholar
    • Export Citation
  • 63. Langlais PJ, Zhang SX. Cortical and subcortical white matter damage without Wernicke's encephalopathy after recovery from thiamine deficiency in the rat. Alcohol Clin Exp Res 1997; 21: 434443.

    • Search Google Scholar
    • Export Citation
  • 64. Chen KT, Chiou ST, Chang YC, et al. Cardiac beriberi among illegal mainland Chinese immigrants. J Int Med Res 2001; 29: 3740.

  • 65. Klein M, Weksler N, Gurman GM. Fatal metabolic acidosis caused by thiamine deficiency. J Emerg Med 2004; 26: 301303.

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Clinical evaluation and biochemical analyses of thiamine deficiency in Pacific harbor seals (Phoca vitulina) maintained at a zoological facility

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  • 1 Sea World Orlando, 7007 Sea World Dr, Orlando, FL 32821.
  • | 2 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 3 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 4 Sea World San Diego, 500 Sea World Dr, San Diego, CA 92109.
  • | 5 Sea World Orlando, 7007 Sea World Dr, Orlando, FL 32821.
  • | 6 Florida Aquarium, 701 Channelside Dr, Tampa, FL 33602.
  • | 7 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 8 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 9 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 10 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 11 California Animal Health and Food Safety Laboratory, 620 W Health Sciences Dr, Davis, CA 95616.
  • | 12 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 13 Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, 2825 50th St, Sacramento, CA 95817.

Abstract

Objective—To determine thiamine-dependent enzyme activities in various tissue samples of Pacific harbor seals (Phoca vitulina) and thiaminase activities in dietary fish.

Design—Cross-sectional study.

Animals—11 Pacific harbor seals with thiamine deficiency and 5 control seals.

Procedures—Seals underwent evaluation to rule out various diseases and exposure to toxins. For seals that died, measurement of thiamine-dependent enzymes in liver and brain samples and determination of mitochondrial DNA (mtDNA) copy number in liver, brain, and muscle samples were performed. Thiaminase activity in dietary fish was determined.

Results—8 seals with thiamine deficiency died. Affected seals typically had acute neurologic signs with few nonspecific findings detected by means of clinicopathologic tests and histologic examination of tissue samples. Thiamine-dependent enzyme activities in liver samples of affected seals were significantly lower than those in control liver samples. The primary activation ratios and latencies for enzymes indicated that brain tissue was more affected by thiamine deficiency than liver tissue. Activities of pyruvate dehydrogenase were more affected by thiamine deficiency than those of transketolase and ketoglutarate dehydrogenase. For control seals, the mtDNA copy number in muscle samples was significantly lower than that for affected seals; conversely, the copy number in control liver samples was significantly greater than that of affected seals. Thiaminase activity was substantially higher in smelt than it was in other types of dietary fish.

Conclusions and Clinical Relevance—Results of analyses in this study confirmed a diagnosis of thiamine deficiency for affected seals resulting from high thiaminase activity in dietary fish, inadequate vitamin administration, and increased thiamine demand caused by pregnancy and lactation.

Abstract

Objective—To determine thiamine-dependent enzyme activities in various tissue samples of Pacific harbor seals (Phoca vitulina) and thiaminase activities in dietary fish.

Design—Cross-sectional study.

Animals—11 Pacific harbor seals with thiamine deficiency and 5 control seals.

Procedures—Seals underwent evaluation to rule out various diseases and exposure to toxins. For seals that died, measurement of thiamine-dependent enzymes in liver and brain samples and determination of mitochondrial DNA (mtDNA) copy number in liver, brain, and muscle samples were performed. Thiaminase activity in dietary fish was determined.

Results—8 seals with thiamine deficiency died. Affected seals typically had acute neurologic signs with few nonspecific findings detected by means of clinicopathologic tests and histologic examination of tissue samples. Thiamine-dependent enzyme activities in liver samples of affected seals were significantly lower than those in control liver samples. The primary activation ratios and latencies for enzymes indicated that brain tissue was more affected by thiamine deficiency than liver tissue. Activities of pyruvate dehydrogenase were more affected by thiamine deficiency than those of transketolase and ketoglutarate dehydrogenase. For control seals, the mtDNA copy number in muscle samples was significantly lower than that for affected seals; conversely, the copy number in control liver samples was significantly greater than that of affected seals. Thiaminase activity was substantially higher in smelt than it was in other types of dietary fish.

Conclusions and Clinical Relevance—Results of analyses in this study confirmed a diagnosis of thiamine deficiency for affected seals resulting from high thiaminase activity in dietary fish, inadequate vitamin administration, and increased thiamine demand caused by pregnancy and lactation.

Contributor Notes

Supported in part by NIEHS R01-ES011269 provided to Dr. Giulivi.

The authors thank Dr. Catherine Richter for providing positive control samples for quantitative PCR assays, Dr. Nancy Stedman for assistance with performance of harbor seal necropsies, Alice Jones and Kristen Clark for assistance with treatment of seals and collection of data, and Dana Granger and Megan Casey for assistance with preparation of DNA samples.

Address correspondence to Dr. Giulivi (cgiulivi@ucdavis.edu).