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Principles of Toxicologic Clinical Pathology

  • Adam AulbachEmail author
  • Laura Cregar
Chapter
  • 126 Downloads

Abstract

Clinical pathology is an important aspect of safety testing in nonclinical toxicology studies. Standard analyses include hematology, coagulation, clinical chemistry, and urinalysis testing. The results of these evaluations help corroborate clinical observations and histopathologic findings, provide insight into the No-observed Adverse Effect Level (NOAEL), characterize the monitorability of test article-related changes, and, in some instances, provide translational biomarkers for human clinical studies. Because data can be collected throughout the course of a study, the temporal relationship of test article-related findings can also be elucidated. It is critical to understand the relationship between clinical pathology test results and findings obtained from microscopic pathology evaluations. The differences between clinical and anatomic pathology may at first seem considerable but fundamentally are nothing more than using different testing modalities to conduct evaluations on the same organ systems.

Key words

Toxicologic clinical pathology Hematology Clinical chemistry Coagulation Urinalysis Biomarkers 

References

  1. Amacher DE, Schomaker SJ, Burkhardt JE (1998) The relationship among microsomal enzyme induction, liver weight, and histological change in rat toxicology studies. Food Chem Toxicol 36:831–839PubMedCrossRefPubMedCentralGoogle Scholar
  2. Amacher DE, Schomaker SJ, Burkhardt JE (2001) The relationship among enzyme induction, liver weight, and histological change in beagle toxicology studies. Food Chem Toxicol 39:817–825PubMedCrossRefPubMedCentralGoogle Scholar
  3. Ameri M (2010) Laboratory diagnosis of malaria in nonhuman primates. Vet Clin Pathol 39(1):5–19PubMedCrossRefPubMedCentralGoogle Scholar
  4. Antman E, Bassand J, Klein W, Ohman M, Sendon J, Ryden L, Simoons M, Tendera M (2000) Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: The Joint European Society of Cardiology/American College of Cardiology Committee. J Am Coll Cardiol 36:959–969PubMedCrossRefPubMedCentralGoogle Scholar
  5. Apple F, Murakami M, Ler R, Walker D, York M (2008) Analytical characteristics of commercial cardiac Troponin I and t immunoassays in serum from rats, dogs, and monkeys with induced acute myocardial injury. Clin Chem 54(12):1982–1989PubMedCrossRefPubMedCentralGoogle Scholar
  6. Aronoff SL, Berkowitz K, Shreiner B, Want L (2004) Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr 17(3):183–190CrossRefGoogle Scholar
  7. Aulbach A, Cirino K, Holland K, Denham S (2012) Interference of activated partial thromboplastin time assays by polyethylene glycol conjugated protein compounds. Poster abstract 31st annual STP meeting, June 2012, Boston MAGoogle Scholar
  8. Aulbach A, Schultze E, Tripathi N, Hall R, Logan M, Meyer D (2015) Factors affecting urine reagent strip blood results in dogs and nonhuman primates and interpretation of urinalysis in preclinical toxicology studies: a Multi-Institution Contract Research Organization and BioPharmaceutical Company Perspective. Vet Clin Pathol 44(2):229–233PubMedCrossRefPubMedCentralGoogle Scholar
  9. Aulbach A, Provencher A, Tripathi N (2017) Influence of study design variables on clinical pathology data. Toxicol Pathol 45(2):288–295PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bauer JE (1996) Comparative lipid and lipoprotein metabolism. Vet Clin Pathol 25(2):49–55CrossRefGoogle Scholar
  11. Bay M, Kirk V, Parner J, Hassager C, Nielsen H, Krogsgaard K, Trawinski J, Boesgaard J, Aldershvile J (2003) NT-proBNP: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function. Heart 89(2):150–154PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bennett J, Gossett K, McCarthy M, Simpson E (1992) Effects of ketamine hydrochloride on serum biochemical and hematologic variables in rhesus monkeys (Macaca mulatta). Vet Clin Pathol 21:15–18PubMedCrossRefPubMedCentralGoogle Scholar
  13. Bertinchant J, Robert E, Polge A, Marty-Double C, Fabbro-Peray P, Poirey S, Aya G, Juan J, Ledermann B, de la Coussaye J, Dauzat M (2000) Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoproterenol-induced cardiac injury in rats. Clin Chim Acta 298(1–2):13–28PubMedCrossRefPubMedCentralGoogle Scholar
  14. Bertinchant J, Polge A, Juan J, Oliva-Lauraire M, Giuliani I, Marty-Double C, Burdy J, Fabbro-Peray P, Laprade M, Bali J, Granier C, Dauzat M (2003) Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings. Clin Chim Acta 329:39PubMedCrossRefPubMedCentralGoogle Scholar
  15. Blair PC, Thompson MB, Wilson RE, Esber HH, Maronpot RR (1988) Correlation of changes in serum analytes and hepatic histopathology in rats exposed to carbon tetrachloride. J Comp Pathol 98:381–404CrossRefGoogle Scholar
  16. Boone L, Meyer D, Cusick P, Ennulat D, Provencher Bolliger A, Everds N, Meador V, Elliott G, Honor D, Bounous D, Jordan H (2005) Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies. Vet Clin Pathol 34(3):182–188PubMedCrossRefPubMedCentralGoogle Scholar
  17. Cardinet G (1997) Skeletal muscle function. In: Kaneko J, Harvey J, Bruss M (eds) Clinical biochemistry of domestic animals, 5th edn. Academic Press, San DiegoGoogle Scholar
  18. Carrasco L, Madsen LW, Salguero FJ, Núñez A, Sánchez-Cordón O, Bollen P (2003) Immune complex-associated thrombocytopenic purpura syndrome in sexually mature Göttingen Minipigs. J Comp Pathol 128:25–32PubMedCrossRefPubMedCentralGoogle Scholar
  19. Chandler M (1992) Pediatric normal blood values. In: Kirk RW, Bonagura JD (eds) Kirk’s current veterinary therapy, XI edn. WB Saunders, PhiladelphiaGoogle Scholar
  20. Cheung B (1997) Plasma concentration of brain natriuretic peptide is related to diastolic function in hypertension. Clin Exp Pharmacol Physiol 24:966–968PubMedCrossRefPubMedCentralGoogle Scholar
  21. Chmurzyńska A (2006) The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet 47(1):39–48PubMedCrossRefPubMedCentralGoogle Scholar
  22. Chow C, Cross C, Kaneko J (1977) Lactate dehydrogenase activity and isoenzyme pattern in lungs, erythrocytes, and plasma of ozoneexposed rats and monkeys. J Toxicol Environ Health 3:877–884PubMedCrossRefPubMedCentralGoogle Scholar
  23. Clements P, Brady S, York M, Berridge B, Mikaelian I, Nicklaus R, Gandhi M, Roman I, Stamp C, Davies D, McGill P, Williams T, Pettit S, Walker D, ILSI HESI Cardiac Troponins Working Group, Turton J (2010) Time course characterization of serum cardiac troponins, heart fatty acid binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat. Toxicol Pathol 38:703PubMedCrossRefPubMedCentralGoogle Scholar
  24. Clerico A, Emdin M (2004) Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: a review. Clin Chem 50:133–150Google Scholar
  25. Clinical and Laboratory Standards Institute (2008) Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd edn. CLSI, WayneGoogle Scholar
  26. Cray C, Zaias J, Altman NH (2009) Acute phase response in animals: a review. Comp Med 59(6):517–526PubMedPubMedCentralGoogle Scholar
  27. DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC (2013) Diabetes Care 35(10):3169–3176CrossRefGoogle Scholar
  28. Eckersall PD (2008) Proteins, proteomics, and the dysproteinemias. In: Kaneko JJ, Harvey JW, Bruss ML (eds) Clinical biochemistry of domestic animals, 6th edn. Elsevier, BurlingtonGoogle Scholar
  29. Ellis A, Little T, Zaki R, Masud A, Klocke F (1985) Patterns of myoglobin release after reperfusion of injured myocardium. Circulation 72:639–647PubMedCrossRefPubMedCentralGoogle Scholar
  30. Ennulat D, Adler S (2015) Recent successes in the identification, development, and qualification of translational biomarkers: the next generation of kidney injury biomarkers. Toxicol Pathol 43:62–69PubMedCrossRefPubMedCentralGoogle Scholar
  31. Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Floey GL, Rosol TJ, Sellers T (2013) Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol 41:560–614PubMedCrossRefPubMedCentralGoogle Scholar
  32. Fontanet H, Trask R, Haas R, Strauss A, Abendschein D, Billadello J (1991) Regulation of expression of M, B, and mitochondrial creatine kinase mRNAs in the left ventricle after pressure overload in rats. Circ Res 68:1007–1012PubMedCrossRefPubMedCentralGoogle Scholar
  33. Food and Drug Administration. Guidance for industry and other stakeholders. Toxicological principles for the safety assessment of food ingredients. Redbook 2000: IV.B.1 General guidelines for designing and conducting toxicity studies: Center for Food Safety and Applied Nutrition, 2003. Available at: http://www.fda.gov/
  34. Franco RS (2012) Measurement of red cell lifespan and aging. Transfus Med Hemother 39(5):302–307PubMedPubMedCentralCrossRefGoogle Scholar
  35. Fry MM (2010a) Acquired platelet dysfunction. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, AmesGoogle Scholar
  36. Fry MM (2010b) Anemia of inflammatory, neoplastic, renal and endocrine diseases. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, AmesGoogle Scholar
  37. Gautier JC, Gury T, Guffroy M, Khan-Malek R, Hoffman D, Petit S, Harpur E (2014) Normal ranges and variability of novel urinary renal biomarkers in Sprague-Dawley rats: comparison of constitutive values between males and females and across assay platforms. Toxicol Pathol 42:1092–1104PubMedCrossRefPubMedCentralGoogle Scholar
  38. Ghani F, Wu A, Graff L, Petry C, Armstrong G, Prigent F, Brown M (2000) Role of heart-type fatty acid-binding protein in early detection of acute myocardial infarction. Clin Chem 46:718–719PubMedCrossRefPubMedCentralGoogle Scholar
  39. Gruys E, Toussaint MJM, Niewold TA, Koopmans SJ (2005) Acute phase reaction and acute phase proteins. J Zhejiang Univ Sci B 6(11):1045–1105PubMedPubMedCentralCrossRefGoogle Scholar
  40. Haley PJ (2013) Lymphoid system. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology nonclincial safety assessment. CRC Press, Boca RatonGoogle Scholar
  41. Hall R (2001) Principles of clinical pathology for toxicity studies. In: Hayes W (ed) Principles and methods of toxicology, 4th edn. Taylor and Francis, PhiladelphiaGoogle Scholar
  42. Hall RL (2013) Principles of clinical pathology. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology nonclincial safety assessment. CRC Press, Boca RatonGoogle Scholar
  43. Hammer AS (1991) Thrombocytosis in dogs and cats: a retrospective study. Comp Haematol Int 1:181–186CrossRefGoogle Scholar
  44. Hard G, Banton M, Bretzlaff R, Dekant W, Fowles J, Mallett A, McGregor D, Roberts K, Sielken R, Valdez-Flores C, Cohen S (2013) Consideration of rat chronic progressive nephropathy in regulatory evaluations for carcinogenicity. Toxicol Sci 132(2):268–275PubMedCrossRefPubMedCentralGoogle Scholar
  45. Hironaka E, Hongo M, Azegami M, Yanagisawa S, Owa M, Hayama M (2003) Effects of angiotensin-converting enzyme inhibition on changes in left ventricular myocardial creatine kinase system after myocardial infarction: their relation to ventricular remodeling and function. Jpn Heart J 44:537–546PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hubert MF, Laroque P, Gillet JP, Keenan KP (2000) The effects of diet, ad libitum feeding and moderate and severe dietary restriction on body weight, survival, clinical pathology parameters, and cause of death in control Sprague-Dawley rats. J Toxicol Sci 58:195–207CrossRefGoogle Scholar
  47. Johnston SD, Root Kustritz MV, Olson PN (2001) Canine pregnancy. In: Johnston SD, Root Kustritz MV, Olson PN (eds) Canine and Feline theriogenology. WB Saunders, PhiladelphiaGoogle Scholar
  48. Kaneko JJ (2008) Carbohydrate metabolism and its diseases. In: Kaneko JJ, Harvey JW, Bruss ML (eds) Clinical biochemistry of domestic animals, 6th edn. Elsevier, BurlingtonGoogle Scholar
  49. Katsuno K, Fujimori Y, Takemura Y, Hiratochi M, Itoh F, Komatsu Y, Fujikura H, Isaji M (2007) Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 320:323–330PubMedCrossRefPubMedCentralGoogle Scholar
  50. Katus H, Yasuda T, Gold H, Leinbach R, Strauss H, Waksmonski C, Haber E, Khaw B (1984) Diagnosis of acute myocardial infarction by detection of circulating cardiac myosin light chains. Am J Cardiol 54(8):964–997CrossRefGoogle Scholar
  51. Kramer J, Hoffman W (1997) Clinical enzymology. In: Kaneko, Harvey, Bruss (eds) Clinical biochemistry of domestic animals, 5th edn. Academic Press, San DiegoGoogle Scholar
  52. Kurata M, Sasayama Y, Yamasaki N, Kitazawa I, Hamada Y, Horii I (2003) Mechanism for shortening PT and APTT in dogs and rats – effect of fibrinogen on PT and APTT. J Toxicol Sci 28(5):439–443PubMedCrossRefPubMedCentralGoogle Scholar
  53. Landi MS, Kissinger JT, Campbell SA, Kenney CA, Jenkins EL Jr (1990) The effects of four types of restraint on serum alanine aminotransferase and aspartate aminotransferase in the Macaca fascicularis. J Am Coll Toxicol 9:517–523CrossRefGoogle Scholar
  54. Lang C, Prasad N, McAlpine H (1994) Increased plasma levels of brain natriuretic peptide in patients with isolated diastolic dysfunction. Am Heart J 127:1635–1636PubMedCrossRefPubMedCentralGoogle Scholar
  55. Levin S, Selmer D, Ruben Z (1993) Effects of two weeks of feed restriction on some common toxicologic parameters in Sprague-Dawley rats. Toxicol Pathol 21(1):1–14PubMedCrossRefPubMedCentralGoogle Scholar
  56. MacDonald K, Kittleson M, Munro C, Kass P (2003) Brain natriuretic peptide concentration in dogs with heart disease and congestive heart failure. J Vet Intern Med 17:172–177PubMedCrossRefPubMedCentralGoogle Scholar
  57. Maratea KA, Snyder PW, Stevenson GW (2003) Vascular lesions in nine Göttingen minipigs with thrombocytopenic purpura syndrome. Vet Pathol 43:447–454CrossRefGoogle Scholar
  58. McMichael M (2005) Primary hemostasis. J Vet Emerg Crit Care 15:1–8CrossRefGoogle Scholar
  59. Metzger J, Westfall M (2004) Covalent and noncovalent modification of thin filament action. The essential role of troponins in cardiac muscle regulation. Circ Res 94:146–158PubMedCrossRefPubMedCentralGoogle Scholar
  60. Meyer DJ, Harvey JW (2004) Hepatobiliary and skeletal muscle enzymes and liver function tests. In: Meyer DJ, Harvey JW (eds) Veterinary laboratory medicine: interpretation and diagnosis, 3rd edn. Saunders, St. LouisGoogle Scholar
  61. Mizuno Y, Yoshimura M, Harada E (2000) Plasma levels of A and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic dilated cardiomyopathy. Am J Cardiol 86:1036–1040PubMedCrossRefPubMedCentralGoogle Scholar
  62. Morgan ET (1997) Regulation of cytochromes P450 during inflammation nd infection. Drug Metab Rev 29(4):1129–1188PubMedCrossRefPubMedCentralGoogle Scholar
  63. Moriyama T, Tsujioka S, Ohira T, Nonaka S, Ikeda H, Sugiura H, Tomohiro M, Samura K, Nishikibe M (2008) Effects of reduced food intake on toxicity study parameters in rats. J Toxicol Sci 33(5):537–547PubMedCrossRefPubMedCentralGoogle Scholar
  64. Nathwani R, Pais S, Reynolds T, Kaplowitz N (2005) Serum alanine aminotransferase in skeletal muscle diseases. Hepatology 41(2):380–382PubMedCrossRefPubMedCentralGoogle Scholar
  65. O’Brien PJ, Slaughter MR, Polley SR, Kramer K (2002) Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. Lab Anim 36:313–321PubMedCrossRefPubMedCentralGoogle Scholar
  66. Ochi T, Yamada A, Nafanuma Y, Nishina N, Koyama H (2016) Effect of road transportation on the serum biochemical parameters of cynomolgus monkeys and beagle dogs. J Vet Med Sci 78:889–893PubMedPubMedCentralCrossRefGoogle Scholar
  67. Olson H, Betton G, Robinson G et al (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67PubMedCrossRefPubMedCentralGoogle Scholar
  68. Olver CS (2010) Erythropoiesis. In: Weiss DJ, Wardrop KM (eds) Shalms veterinary hematology, 6th edn. Wiley Blackwell, AmesGoogle Scholar
  69. Organisation for Economic Co-operation and Development (OECD) (2009) OECD guidelines for the testing of chemicals, section 4: health effects. Publications de l’OCDEGoogle Scholar
  70. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S (2008) The current state of serum biomarkers of hepatotoxicity. Toxicology 245:194–205PubMedCrossRefPubMedCentralGoogle Scholar
  71. Ozer JS, Chetty R, Kenna G, Koppiker N, Karamjeet P, Li D, Palandra J, Lanevschi A, Souberbielle BE, Ramaiah S (2010) Recommendations to qualify biomarker candidates of drug-induced liver injury. Biomark Med 4(3):475–483PubMedCrossRefPubMedCentralGoogle Scholar
  72. Pahan K (2006) Lipid-lowering drugs. Cell Mol Life Sci 63(10):1165–1178PubMedPubMedCentralCrossRefGoogle Scholar
  73. Perigard CJ, Parrula MCM, Larkin MH, Gleason CR (2016) Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques. Vet Clin Pathol 45(2):232–243PubMedCrossRefPubMedCentralGoogle Scholar
  74. Radin MJ, Wellman ML (2010) Granulopoisis. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, AmesGoogle Scholar
  75. Ramaiah SK (2011) Preclinical safety assessment: current gaps, challenges, and approaches in identifying translatable biomarkers of drug-induced liver injury. Clin Lab Med 31(1):161–172PubMedCrossRefPubMedCentralGoogle Scholar
  76. Ramaiah L, Tomlinson L, Tripathi et al (2017) Principles for assessing adversity on toxicologic clinical pathology. Toxicol Pathol 45(2):260–266PubMedCrossRefPubMedCentralGoogle Scholar
  77. Ramaiah L, Bounous DI, Elmore SA (2018) Hematopoietic system. In: Wallig MA, Haschek WM, Rousseaux CG, Bolon B, Mahler BW (eds) Fundamentals of toxicologic pathology, 3rd edn. Academic Press, LondonGoogle Scholar
  78. Randolph JF, Peterson ME, Stokol (2010) Erythrocytosis and polycythemia. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, AmesGoogle Scholar
  79. Reagan WJ, Irizarry-Rovira A, Poitout-Belissent F et al (2011) Best practices for evaluation of bone marrow in nonclincial toxicity studies. Toxicol Pathol 39:435–488PubMedCrossRefPubMedCentralGoogle Scholar
  80. Renard D, Rosselet A (2017) Drug-induced hemolytic anemia: pharmacological aspects. Transfus Clin Biol 24:110–114PubMedCrossRefPubMedCentralGoogle Scholar
  81. Rortveit R, Saevik B, Eggertsdottir A, Skancke E, Lingaas F, Thoresesn S, Jansen J (2015) Age-related changes in hematologic and serum biochemical variables in dogs aged 16–60 days. Vet Clin Pathol 44:47–57PubMedCrossRefPubMedCentralGoogle Scholar
  82. Rosset E, Rannou B, Casseleux G, Chalvet-Monfray K, Buff S (2012) Age-related changes in biochemical and hematologic variables in Borzoi and Beagle puppies from birth to 8 weeks. Vet Clin Pathol 41:272–282PubMedCrossRefPubMedCentralGoogle Scholar
  83. Russell KE (2010) Platelet kinetics and laboratory evaluation of thrombocytopenia. In: Weiss DJ, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, AmesGoogle Scholar
  84. Sakai A, Izumi M, Minami T, Komaki T, Matsumoto N, Asahi K, Yunomae A (2016) Experimental procedures increase the IL-6 and stress markers in cynomolgus monkey. Society of toxicology annual meeting, New Orleans, LAGoogle Scholar
  85. Schafer AI (1995) Effects of nonsteroidal anti-inflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol 35:209–219PubMedCrossRefPubMedCentralGoogle Scholar
  86. Schnellman R (2008) Toxic responses of the kidney. In: Casarett, Doulls (eds) Toxicology: the basic science of poisons, 7th edn. McGraw-Hill, New YorkGoogle Scholar
  87. Schomaker S, Warner R, Bock J et al (2013) Assessment of emerging biomarkers of liver injury in human subjects. Toxicol Sci 132(2):276–283PubMedCrossRefPubMedCentralGoogle Scholar
  88. Schultze A, Carpenter K, Wians F, Agee S, Minyard J, Lu Q, Konrad R, Todd J (2009) Longitudinal studies of cardiac Troponin-I concentrations in serum from male Sprague Dawley rats: baseline reference ranges and effects of handling and Placebo dosing on biological variability. Toxicol Pathol 37:754–760PubMedCrossRefPubMedCentralGoogle Scholar
  89. Schultze AE, Walker DB, Turk JR, Tarrant JM, Brooks MB, Pettit SD (2013) Current practices in preclinical drug development: gaps in hemostasis testing to assess risk of thromboembolic injury. Toxicol Pathol 41:445–453PubMedCrossRefPubMedCentralGoogle Scholar
  90. Sharkey S, Murakami M, Smith S, Apple F (1991) Canine myocardial creatine kinase isoenzymes after chronic coronary artery occlusion. Circulation 84:333–340PubMedCrossRefPubMedCentralGoogle Scholar
  91. Sheehan J, Patten D, Mowat V (2014) Rat. In: Green O, Healing G (eds) Nonclinical vascular infusion technology volume II: the techniques. CRC Press, Boca RatonGoogle Scholar
  92. Siemens Clinitek Atlas 10 Reagent Pak Package InsertGoogle Scholar
  93. Simpson J, Labugger R, Hesketh G, D’Arsigny C, O’Donnell D, Matsumoto M, Collier C, Iscoe S, Van Eyk J (2002) Differential detection of skeletal Troponin I isoforms in serum of a patient with rhabdomyolysis: markers of muscle injury. Clin Chem 48(7):1112–1114PubMedCrossRefPubMedCentralGoogle Scholar
  94. Siska W, Meyer D, Schultze A, Brandoff C (2017) Identification of contaminant interferences with cause positive urine reagent test strip reactions in a cage setting for the laboratory-housed nonhuman primate, Beagle dog, and Sprague Dawley rat. Vet Clin Pathol 46(1):85–90PubMedCrossRefPubMedCentralGoogle Scholar
  95. Smith SA (2009) The cell-based model of coagulation. J Vet Emerg Crit Care 19(1):3–10CrossRefGoogle Scholar
  96. Stanislaus D, Andersson H, Chapin R, Creasy D, Ferguson D, Gilbert M, Rosol TJ, Waite Boyce R, Wood C (2012) Society of toxicologic pathology position paper: review series: assessment of circulating hormones in nonclincial toxicity studies: general concepts and considerations. Toxicol Pathol 40:943–950PubMedCrossRefPubMedCentralGoogle Scholar
  97. Stockham S, Scott M (2008a) Erythrocytes. In: Stockham S, Scott M (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, pp 639–669Google Scholar
  98. Stockham S, Scott M (2008b) Hemostasis. In: Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, AmesGoogle Scholar
  99. Stockham S, Scott M (2008c) Enzymes. In: Stockham S, Scott M (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, pp 639–669Google Scholar
  100. Stockham S, Scott M (2008d) Liver function. In: Stockham S, Scott M (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, pp 639–669Google Scholar
  101. Stockham S, Scott M (2008e) Urinary system. In: Stockham S, Scott M (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, pp 639–669Google Scholar
  102. Stockham S, Scott M (2008f) Calcium, phosphorus, magnesium, and their regulatory hormones. In: Stockham S, Scott M (eds) Fundamentals of veterinary clinical pathology, 2nd edn. Blackwell, Ames, pp 639–669Google Scholar
  103. Thorn CE (2000) Normal hematology of the pig. In: Feldman BF, Zinkl JG, Jain NC (eds) Schalm’s veterinary hematology, 5th edn. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  104. Tomlinson L, Boone L, Ramaiah L, Penraat K, von Beust B, Ameri M, Poitout-Belissent F, Weingand K, Workman H, Aulbach A, Meyer D, Brown D, MacNeill A, Bolliger A, Bounous D (2013) Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries. Vet Clin Pathol 23(3):252–256CrossRefGoogle Scholar
  105. Tonomura Y, Matsushima S, Kashiwagi E, Fujisawa K, Takagi S, Nishimura Y, Fukushima R, Torii M, Matsubara M (2012) Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity and musculoskeletal toxicity in rats. Toxicology 302:179–189PubMedCrossRefPubMedCentralGoogle Scholar
  106. Traslavina RP, King EJ, Loar AS, Riedel ER, Garvey MS, Ricart-Arbona R, Wolf FR, Couto SS (2010) Euthanasia by CO2 inhalation affects potassium levels in mice. J Am Assoc Lab Anim Sci 49(3):316–322PubMedPubMedCentralGoogle Scholar
  107. Tripathi J, Gregory C, Latimer K (2011) Urinary system. In: Latimer K (ed) Duncan & Prasse’s veterinary laboratory medicine: clinical pathology, 5th edn. Wiley-Blackwell, AmesGoogle Scholar
  108. Vlasakova K, Erdos Z, Troth S, McNulty K, Chapeau-Campredon V, Mokrzycki N, Muniappa N, Gu Y, Holder D, Bailey W, Sistare F, Glaab W (2014) Evaluation of the relative performance of 12 urinary biomarkers for renal safety across 22 rat sensitivity and specificity studies. Toxicol Sci 8(1):3–20CrossRefGoogle Scholar
  109. Vogler M, Hamali HA, Sun XM, Bampton ETW, Dinsdale D, Snowden RT, Dyer MJS, Goodall AH, Cohen GM (2011) BCL2/BCL-XL inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood 117:7145–7154PubMedCrossRefPubMedCentralGoogle Scholar
  110. Walker D (2006) Serum chemical biomarkers of cardiac injury for nonclinical safety testing. Toxicol Pathol 34:94PubMedCrossRefPubMedCentralGoogle Scholar
  111. Weingand K, Bloom J, Carakostas M, Hall R, Helfrich M, Latimer K, Levine B, Neptun D, Rebar A, Stitzel K, Troup C (1992) Clinical pathology testing recommendations for nonclinical toxicity and safety studies. Toxicol Pathol 20(3):529–543Google Scholar
  112. Weingand K, Brown G, Hall R, Davies D, Gossett K, Neptun D, Waner T, Matsuzawa T, Salemink P, Froelke W, Provost J, Dal Negro G, Batchelor J, Nomura M, Groetsch H, Boink A, Kimball J, Woodman D, York M, Fabianson-Johnson E, Lupart M, Melloni E (1996) Harmonization of animal clinical pathology testing in toxicity and safety studies. Fundam Appl Toxicol 29:198–201PubMedCrossRefPubMedCentralGoogle Scholar
  113. Wolford S, Schroer R, Gohs F, Gallo P, Brodeck M, Falk H, Ruhren R (1987) Age-related changes in serum chemistry and hematology values in normal Sprague-Dawley rats. Fundam Appl Toxicol 8:80–88PubMedCrossRefPubMedCentralGoogle Scholar
  114. Wolford S, Schroer R, Gohs F, Gallo P, Falk H, Dente A (1998) Effect of age on serum chemistry profile, electrophoresis and thyroid hormones in beagle dogs two weeks to one year of age. Vet Clin Pathol 17:35–42CrossRefGoogle Scholar
  115. Yasue H, Yoshimura M, Sumida H et al (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90:195–203PubMedCrossRefPubMedCentralGoogle Scholar
  116. Yin W, Carballo-Jane E, McLaren DG, Mendoza VH, Gagen K, Geoghagen NS, McNamara LA, Gorski JN, Eiermann GJ, Petrov A, Wolff M, Tong X, Wilsie LC, Akiyama TE, Chen J, Thankappan A, Xue J, Ping X, Andrews G, Wickham LA, Gai CL, Trinh T, Kulick AA, Donnelly MJ, Voronin GO, Rosa R, Cumiskey A, Bekkari K, Mitnaul LJ, Puig O, Chen F, Raubertas R, Wong PH, Hansen BC, Koblan KS, Roddy TP, Hubbard BK, Strack AM (2012) Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res 53:51–65PubMedPubMedCentralCrossRefGoogle Scholar
  117. Yoffey J, Courtice F (1970) Lymphatics, lymph and the lymphomyeloid complex. Academic Press, LondonGoogle Scholar
  118. York M, Scudamore C, Brady S, Chen C, Wilson S, Curtis M, Evans G, Griffiths W, Whayman M, Williams T, Turton J (2007) Characterization of troponin responses in isoproterenol-induced cardiac injury in the Hanover Wistar rat. Toxicol Pathol 35:606PubMedCrossRefPubMedCentralGoogle Scholar
  119. Young JK, Hall RL, O’Brien P, Strauss V, Vahle JL (2011) Best practices for clinical pathology testing in carcinogenicity studies. Toxicol Pathol 39:429–434PubMedCrossRefPubMedCentralGoogle Scholar
  120. Zhen E, Berna M, Jin Z, Pritt M, Watson D, Ackermann B, Hale J (2007) Quantification of heart fatty acid–binding protein as a biomarker for drug-induced cardiac and musculoskeletal necroses. Proteomics 1(7):661–671PubMedPubMedCentralGoogle Scholar
  121. Zollner G, Marschall HU, Wagner M, Trauner M (2006) Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations. Mol Pharm 3:231–251PubMedCrossRefPubMedCentralGoogle Scholar
  122. Zucker SD, Qin X, Rouster SD, Yu F, Green RM, Keshavan P, Feinberg J, Sherman KE (2001) Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A 98:12671–12676PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Charles River Laboratories, Inc.MattawanUSA

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