Analytical Characteristics of Commercial Cardiac Troponin I and T Immunoassays in Serum from Rats, Dogs, and Monkeys with Induced Acute Myocardial Injury

Apple, Fred S.; Murakami, MaryAnn M.; Ler, Ranka; Walker, Dana B.; York, Malcolm

doi:10.1373/clinchem.2007.097568

Cited by 79 publications

(61 citation statements)

References 23 publications

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“…Challenges remain with regard to preclinical applications, including assessment of a suitable cutoff for irreversible myocardial injury, optimal timing of sample collection (Adamcova et al 2005), relatively limited data sets for animals, and lack of standardization between various immunoassays available to measure cTnI concentration. Important differences exist in species-specific cross-reactivity of the antibodies used in the assays available for the measurement of cTnI concentrations in laboratory rats, dogs, and monkeys, as well as the precision and accuracy of the measurements (Apple et al 2008). There is little information available regarding the use of these same assays in mice.…”

Section: Introductionmentioning

confidence: 99%

Qualification of Cardiac Troponin I Concentration in Mouse Serum Using Isoproterenol and Implementation in Pharmacology Studies to Accelerate Drug Development

et al. 2009

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Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in cTnI concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, cTnI concentration was a reliable stand-alone biomarker of cardiac injury and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to cardiotoxicity. Additional attributes, including low cost and rapid turnaround time, made cTnI concentration in serum invaluable for detecting cardiotoxicity, exploring structureactivity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery.

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Section: Introductionmentioning

confidence: 99%

Qualification of Cardiac Troponin I Concentration in Mouse Serum Using Isoproterenol and Implementation in Pharmacology Studies to Accelerate Drug Development

et al. 2009

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“…In the nephrotoxicity biomarker project, the committee assembled data related to urinary markers of nephrotoxicity that had been described and used by others in the field. In 2008 and 2009, the committee worked closely with regulatory agencies to review the literature and address clarifying questions surrounding a proposed set of urinary biomarkers [52]. In 2010 the FDA released a final decision approving the biomarkers and the context in which they can be used [53].…”

Section: Discussionmentioning

confidence: 99%

Validation of Molecular and Genomic Biomarkers of Retinal Drug Efficacy: Use of Ocular Fluid Sampling to Evaluate VEGF

Sharma

Rowe-Rendleman²

2010

Neurochem Res

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The use of tissue- and cell-based methods in developing drugs for retinal diseases is inefficient. Consequently, many aspects of ocular drug therapy for retinal diseases are poorly understood. Biomarkers as prognostic indicators of change are needed to optimize the use of drugs. VEGF is considered an important target of drug therapy and VEGF levels in tissue are indicative of solid tumor growth. However, since many aspects of VEGF as a biomarker of ocular disease have not been validated, it has been difficult to ascertain without invasive procedures whether VEGF in the eye is a biomarker of response to drug therapy. Using published papers, registered clinical trials, and proteomic databases we assessed the earlier evidence for VEGF as an exploratory biomarker of proliferative and vasculopathic disease of the retina and asked whether the molecule has been rigorously validated in clinical trials. The emerging use of aqueous humor sampling has made it possible to explore biomarkers in oculo, and determine whether they are predictive of drug efficacy. We present data supporting the use of aqueous humor to validate drug-signaling pathways and biomarkers in the eye. In addition, we recommend convening a collaborative congress to help standardize the identification, validation, and use of biomarkers in retinal disease.

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“…We supposed that cTnT analyses had an insufficient sensitivity in the present study. Moreover, Apple et al [36] reported that cTnI assays providing a measurable signal in the absence of a cTnT signal in rat, dog and monkey. Additionally, cTnI is more sensitive than cTnT and its values 3-7-fold higher than from cTnT with any given heart damage [37] .…”

Section: Güneş Uyanik Eren Ki̇bar Aslan Onmazmentioning

confidence: 99%

Dilate Kardiyomiyopati, Distemper yada Parvoviral İnfeksiyonlu Köpeklerde Kardiyak Troponinin Hızlı Analizi

Güneş¹,

Uyanik²,

Eren³

et al. 2014

Kafkas Univ Vet Fak Derg

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In this study, concentrations of cardiac troponins (cTnI and cTnT) and using a cassette kit which is a qualitative assay were used to investigate the diagnosis of myocardial damages due to different diseases in dogs. Study groups were composed of dogs with distemper infection (DI) (Group I, n=8), parvoviral infection (PVI) (Group II, n=18) and dilated cardiomyopathy (DCM) (Group III, n=18). Healthy dogs were included for each group as control. Levels of troponins (cTnI, cTnT) were determined by commercially available ELISA kits and cassette kits were used for qualitative assays. The mean concentrations of cTnI in Groups I, II and III were 2.26±0.41 ng/ml, 2.41±0.98 ng/ml and 5.076±1.32 ng/ml, respectively. Positive cTnI and cTnT expressions were determined in groups as 5/8 (62.5%) and 4/8 (50%) in group I; 5/18 (27.7%) and 5/18 (27.7%) in group II and 13/18 (72.2%) and 6/18 (33.3%) in group III, respectively. In healthy control dogs, cTnI and cTnT were determined to be negative. The cTnI concentrations were more reliable cardiac marker in dogs with cardiomyopathy. Moreover, cTnI and cTnT casette kits used in this study may be valuable diagnostic tools to diagnose the myocardial damage in dogs with DI, PVI and DCM for the small animal practioners. Özet Bu çalışmada, köpeklerdeki farklı hastalıklara bağlı miyokardial dejenerasyonların teşhisinde kardiyak troponin (cTnI, cTnT) konsantrasyonları ve kalitatif analiz yapan kaset kitlerinin kullanımı araştırıldı. Çalışma grupları distemper enfeksiyonlu (DE) (Group I, n=8), parvoviral enfeksiyonlu (PVE) (Group II, n=18) ve dilate kardiyomiyopatili (Group III, n=18) köpeklerden oluşturuldu. Her bir grubun kontrolü için sağlıklı köpekler çalışmaya dahil edildi. Ticari ELISA kitleri ile troponin (cTnI, cTnT) düzeyleri belirlendi ve kalitatif analizler için kaset kitler kullanıldı. Grup I, II ve III'de ortalama cTnI düzeyleri sırasıyla 2.26±0.41 ng/ml, 2.41±0.98 ng/ml ve 5.076±1.32 ng/ml idi. Pozitif cTnI ve cTnT varlığı da sırasıyla grup I'de 5/8 (62.5%) ve 4/8 (50%); grup II'de 5/18 (27.7%) ve 5/18 (27.7%), ve grup III'te 13/18 (72.2%) ve 6/18 (33.3%) olarak belirlendi. Sağlıklı kontrol köpeklerinde cTnI ve cTnT testlerinin negatif olduğu belirlendi. Kardiyomiyopatili köpeklerde kalp biyobelirteçleri daha güvenilirdi. Ayrıca cTnI ve cTnT kaset kitlerinin küçük hayvan pratisyenleri için; DE, PVE ve kardiyomiyopatili köpeklerde miyokarditisi belirlemek için faydalı bir teşhis aracı olabileceği belirlendi.

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Analytical Characteristics of Commercial Cardiac Troponin I and T Immunoassays in Serum from Rats, Dogs, and Monkeys with Induced Acute Myocardial Injury

Abstract: BACKGROUND:Information is needed regarding analytical characteristics of cardiac troponin (cTn) assays used in preclinical studies.

Cited by 79 publications

References 23 publications

Qualification of Cardiac Troponin I Concentration in Mouse Serum Using Isoproterenol and Implementation in Pharmacology Studies to Accelerate Drug Development

Qualification of Cardiac Troponin I Concentration in Mouse Serum Using Isoproterenol and Implementation in Pharmacology Studies to Accelerate Drug Development

Validation of Molecular and Genomic Biomarkers of Retinal Drug Efficacy: Use of Ocular Fluid Sampling to Evaluate VEGF

Dilate Kardiyomiyopati, Distemper yada Parvoviral İnfeksiyonlu Köpeklerde Kardiyak Troponinin Hızlı Analizi

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