Abstract:
:There has been a substantial increase in the number and efficacy of laboratory biomarkers for the evaluation of human cardiac injury over the last decade. The advantages of these over traditional laboratory tests have encouraged adoption of comparable markers in nonclinical studies for cardiac injury assessment. Of particular interest are markers that are not only more sensitive and/or specific than traditional parameters for cardiac injury, but also those that may directly bridge human and laboratory animal safety testing. However, a majority of recently developed markers are quantified through antibody-based assays, and cross-reactivity with the comparable analyte in nonhuman samples is difficult to predict and often species-variable. The utility of these novel biomarkers thus, depends upon adequate assay validation with each laboratory species of interest. In contrast, traditional laboratory parameters of cardiac injury lack the properties of an ideal biomarker, but are well established and have an extensive database in nonclinical safety assessment. The current status and utility of both recently developed and traditional biomarkers of cardiac injury in nonclinical testing, and considerations for validation of novel biomarkers of cardiac injury are reviewed.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Walker DBdoi
10.1080/01926230500519816subject
Has Abstractpub_date
2006-01-01 00:00:00pages
94-104issue
1eissn
0192-6233issn
1533-1601pii
R13R5N7025270203journal_volume
34pub_type
杂志文章,评审abstract::Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317751573
更新日期:2018-02-01 00:00:00
abstract::Slc:Wistar male rats treated with human natural tumor necrosis factor alpha (hn TNF-alpha, 3 X 10(5) Japan reference units/kg intravenously) for 3 months showed histologic vacuolation of basophils in the anterior pituitary, hyperplasia of the thyroidal follicular epithelium, and hyperplasia of the testicular interstit...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700403
更新日期:1999-07-01 00:00:00
abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600867750
更新日期:2006-01-01 00:00:00
abstract::Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and d...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500243045
更新日期:2005-01-01 00:00:00
abstract::Recent advances in immunocytochemical techniques allow the localization of specific antigens in tissue sections. The work reported here attempts to evaluate the application of antibody-labeled, disease-related protein, followed by microscopy and computerized image analysis. Using an experimental anti-tumor, polyclonal...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500308
更新日期:1987-01-01 00:00:00
abstract::GJA1 gene (Connexin43, also known as Cx43) is the most abundant gap junction protein isoform in animal cells and is associated with bone development in embryos. The objective of the present work was to evaluate in vivo osteal development in GJA1-deficient fetal mice through determination of the histological and molecu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311422075
更新日期:2011-12-01 00:00:00
abstract::A nondopaminergic antipsychotic agent, 5-ethyl-1,3,8-trimethyl-1H-imidazo]1,2-c]pyrazolo[3,4-e]pyrimidine (TIPP; PD 112488), has been tested for potential toxicity in rats. As part of a preclinical safety evaluation, 10 Wistar rats per sex were administered TIPP as a dietary admixture, receiving doses of 0, 5, 10, 20,...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200106
更新日期:1994-01-01 00:00:00
abstract::Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was ad...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309357946
更新日期:2010-02-01 00:00:00
abstract::Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis t...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308329340
更新日期:2009-02-01 00:00:00
abstract::Progressive renal interstitial fibrosis occurs following tissue injury, resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339602400208
更新日期:1996-03-01 00:00:00
abstract::The relatively high incidence and variety of lesions induced in the upper respiratory tract of rodents by inhalation of xenobiotics has resulted in considerable attention given to the microscopic anatomy of this area. Specific areas of the rodent laryngeal mucosa appear to be more sensitive to inhaled materials and mo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000106
更新日期:1992-01-01 00:00:00
abstract::Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317721748
更新日期:2017-07-01 00:00:00
abstract::In the present study, susceptibility of CB6F1 mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and p53 gene knockout mice (p53 (+/-) mice) to urethane-induced lung carcinogenesis was compared under the same experimental conditions. Both strains were administered 500 ppm urethane in their drinking water for...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590908231
更新日期:2005-01-01 00:00:00
abstract::The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchan...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230390201273
更新日期:2003-07-01 00:00:00
abstract::ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-en...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700203
更新日期:1999-03-01 00:00:00
abstract::Ocular medical devices (MDs) represent a very wide and promising field of human ophthalmology. In preclinical studies evaluating the safety and/or performance of these ocular MDs, the choice of histologic technique and the focus of the histopathologic evaluation method should take into consideration the following aspe...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623318813533
更新日期:2019-04-01 00:00:00
abstract::In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrach...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200118
更新日期:1984-01-01 00:00:00
abstract::High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT val...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314544379
更新日期:2015-04-01 00:00:00
abstract::This report demonstrates the advantages of using a noninvasive soft tissue imaging technique--magnetic resonance imaging (MRI)--to monitor liver regeneration after 70% partial hepatectomy in the rat in a longitudinal manner. Six animals were scanned prior to and on 6 subsequent occasions up to 9 days after surgical re...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230290105811
更新日期:2002-09-01 00:00:00
abstract::This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310396904
更新日期:2011-04-01 00:00:00
abstract::We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623313486317
更新日期:2014-01-01 00:00:00
abstract::Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epith...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000311
更新日期:1992-01-01 00:00:00
abstract::Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous backgroun...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310394211
更新日期:2011-02-01 00:00:00
abstract::Epidemiological associations have been made between the new onset of childhood rhinitis/asthma and exposures to elevated ambient levels of ozone, a commonly encountered gaseous air pollutant. Our laboratory was the first to find that mice repeatedly exposed to ozone develop nasal type 2 immunity and eosinophilic rhini...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623319873872
更新日期:2019-12-01 00:00:00
abstract::This brief review summarizes our current understanding of vasculitis mediated by phlogistic immune complexes. The Arthus reaction and serum sickness both represent experimental models for immune complex disease. Immune complex phenomena occur in conjunction with C3 deficiency of dogs during canine distemper virus infe...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338901700107
更新日期:1989-01-01 00:00:00
abstract::Histopathology of the reproductive system of 76 young adult Dutch Belted and 22 young adult or adult male New Zealand White rabbits was conducted as part of fertility studies. Thirty-five (46%) of the Dutch Belted and 11 (50%) of the New Zealand White males had multifocal vesicular gland basal epithelial cell atypia a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338501300309
更新日期:1985-01-01 00:00:00
abstract::Ribonucleic acid (RNA) interference (RNAi) is a recently discovered phenomenon whereby the introduction of double stranded (ds) RNA into the cytoplasm of the cell results in the specific and efficient degradation of complementary messenger (m) RNA and, therefore, reduced protein production. It was discovered by chance...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230701197107
更新日期:2007-04-01 00:00:00
abstract::Monocrotaline pyrrole (MCTP) is a highly reactive pneumotoxic metabolite of the pyrrolizidine alkaloid plant toxin monocrotaline. When administered to rats, it causes a delayed and progressive lung injury, vascular remodeling, and pulmonary hypertension. Structural remodeling consists of endothelial cell swelling foll...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500405
更新日期:1997-07-01 00:00:00
abstract::The toxicity of polybrominated diphenyl ethers (PBDEs), flame-retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 and continuing to weaning on postnatal day (PND) 21. Offspring from the dams underwent PBDE direct dosing by gav...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311429973
更新日期:2012-01-01 00:00:00
abstract::Biomass burning is a major source of indoor air pollution in rural India. The authors investigated in this study whether cumulative exposures to biomass smoke cause activation of the serine/threonine kinase Akt in airway cells and peripheral blood lymphocytes (PBL). For this, the authors enrolled 87 premenopausal (med...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310385139
更新日期:2010-12-01 00:00:00