abstract：:A factor limiting widespread use of the transgenic rasH2 mouse model for carcinogenicity testing of pharmaceuticals is the paucity of published data on actual drug candidates in rasH2 mice. This report addresses this gap by highlighting rasH2 mouse study data for 10 pharmaceutical candidates. These results were compar...

journal_title：Toxicologic pathology

authors： Nambiar PR,Morton D

更新日期：2013-01-01 00:00:00

abstract：:Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury. Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme biology in response to compounds that cause metabolic adaptive versus hepatotoxic responses will allow for a more accurate assessment of the significance of an ...

journal_title：Toxicologic pathology

authors： Reagan WJ,Yang RZ,Park S,Goldstein R,Brees D,Gong DW

更新日期：2012-12-01 00:00:00

abstract：:Novel urinary protein biomarkers for the detection of acute renal damage, recently accepted by the U.S. Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be validated in practice. Limited data regarding the performance of these acute markers af...

journal_title：Toxicologic pathology

authors： Fuchs TC,Frick K,Emde B,Czasch S,von Landenberg F,Hewitt P

更新日期：2012-10-01 00:00:00

abstract：:The definition of diagnostic thresholds is an important aspect of identification and recording of histopathologic lesions in toxicology studies. Although the primary goal of the pathology examination is to identify and interpret lesions associated with the administration of the test article, the toxicologic pathologis...

journal_title：Toxicologic pathology

authors： Long GG,Hardisty JF

更新日期：2012-10-01 00:00:00

abstract：:Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SH...

journal_title：Toxicologic pathology

authors： Kantner I,Erben RG

更新日期：2012-07-01 00:00:00

abstract：:In non-rodent toxicity studies supporting pharmaceutical or chemical product registration, the value of histopathology evaluation of all tissues from all animals from all dose groups is an ongoing discussion topic among pathologists. This manuscript documents an examination of this topic through a retrospective review...

journal_title：Toxicologic pathology

authors： Weddle DL,Mahrt CR,Schmidt SP

更新日期：2012-07-01 00:00:00

abstract：:Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...

journal_title：Toxicologic pathology

authors： Nambiar PR,Turnquist SE,Morton D

更新日期：2012-06-01 00:00:00

abstract：:2,3-Pentanedione (PD) is a component of artificial butter flavorings. The use of PD is increasing since diacetyl, a major butter flavorant, was associated with bronchiolitis obliterans (BO) in workers and has been removed from many products. Because the toxicity of inhaled PD is unknown, these studies were conducted t...

journal_title：Toxicologic pathology

authors： Morgan DL,Jokinen MP,Price HC,Gwinn WM,Palmer SM,Flake GP

更新日期：2012-04-01 00:00:00

abstract：:A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin...

journal_title：Toxicologic pathology

authors： Pinches MD,Betts CJ,Bickerton SJ,Beattie L,Burdett LD,Thomas HT,Derbyshire NA,Moores M,Price SA

更新日期：2012-04-01 00:00:00

abstract：:Weak peroxisome proliferator-activated receptor (PPAR) α agonists (fibrates) are used to treat dyslipidemia. This study compared the effects of the potent and selective PPARα agonist CP-778875 on peroxisomal β-oxidation and cardiac and/or skeletal muscle injury with those of the weak PPARα agonist fenofibrate. We hypo...

journal_title：Toxicologic pathology

authors： Pettersen JC,Pruimboom-Brees I,Francone OL,Amacher DE,Boldt SE,Kerlin RL,Ballinger WE

更新日期：2012-04-01 00:00:00

abstract：:I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my r...

journal_title：Toxicologic pathology

authors： Kerkvliet NI

更新日期：2012-01-01 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

authors： Dunnick JK,Brix A,Cunny H,Vallant M,Shockley KR

更新日期：2012-01-01 00:00:00

abstract：:Expression of antigens in cells and tissues can be readily studied immunohistochemically with the use of antibodies. A panel of antibodies to cell-specific markers can be used to diagnose lesions, including tumors, in the hematopoietic and lymphoid systems. This review discusses the use of readily available antibodies...

journal_title：Toxicologic pathology

authors： Rehg JE,Bush D,Ward JM

更新日期：2012-01-01 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

authors： Chaible LM,Sanches DS,Cogliati B,Mennecier G,Dagli ML

更新日期：2011-12-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists are used in the treatment of type 2 diabetes mellitus and hyperlipidemias. In carcinogenicity studies, some of these agonists induced hemangiomas/hemangiosarcomas in mice, but not in rats. We hypothesized that increased endothe...

journal_title：Toxicologic pathology

authors： Kakiuchi-Kiyota S,Arnold LL,Yokohira M,Koza-Taylor P,Suzuki S,Varney M,Pennington KL,Cohen SM

更新日期：2011-12-01 00:00:00

abstract：:Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparation...

journal_title：Toxicologic pathology

authors： Whitney KM,Schwartz Sterman AJ,O'Connor J,Foley GL,Garman RH

更新日期：2011-08-01 00:00:00

abstract：:To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5...

journal_title：Toxicologic pathology

authors： Golbar HM,Izawa T,Yano R,Ichikawa C,Sawamoto O,Kuwamura M,Lamarre J,Yamate J

更新日期：2011-08-01 00:00:00

abstract：:High doses of insulin and the insulin analog AspB10 have been reported to increase mammary tumor incidence in female rats likely via receptor-mediated mechanisms, possibly involving enhanced IGF-1 receptor activation. However, insulin and IGF-1 receptor functionality and intracellular signaling in the rat mammary glan...

journal_title：Toxicologic pathology

authors： Hvid H,Fels JJ,Kirk RK,Thorup I,Jensen HE,Hansen BF,Oleksiewicz MB

更新日期：2011-06-01 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

authors： Grassi TF,Rodrigues MA,de Camargo JL,Barbisan LF

更新日期：2011-04-01 00:00:00

abstract：:The objective was to determine the respiratory toxicity of MAP0004, orally inhaled dihydroergotamine (DHE), via inhalation for six months. Forty beagle dogs (twenty females, twenty males) were treated by nose-only inhalation for 182 days. Groups 2 through 5 received MAP0004 (mean doses: 0.045, 0.154, 0.44, 0.825 mg/kg...

journal_title：Toxicologic pathology

authors： Armer TA,Lynch M,Moutvic R,Singer A

更新日期：2011-04-01 00:00:00

abstract：:In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive n...

journal_title：Toxicologic pathology

authors： Damsch S,Eichenbaum G,Looszova A,Lammens L,Feyen B,Van den Bulck K,Knight E,Kelley M,Tonelli A

更新日期：2011-02-01 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

authors： Dunnick JK,Singh B,Nyska A,Peckham J,Kissling GE,Sanders JM

更新日期：2011-02-01 00:00:00

abstract：:Astrocytes assume multiple roles in maintaining an optimally suited milieu for neuronal function. Select astrocytic functions include the maintenance of redox potential, the production of trophic factors, the regulation of neurotransmitter and ion concentrations, and the removal of toxins and debris from the cerebrosp...

journal_title：Toxicologic pathology

authors： Sidoryk-Wegrzynowicz M,Wegrzynowicz M,Lee E,Bowman AB,Aschner M

更新日期：2011-01-01 00:00:00

abstract：:The evaluation of neurotoxic damage involves a unique set of challenges. Vulnerable structures, such as neocortex, hippocampus, spinal cord, and peripheral nerve are complex and sharply differentiated; deficits can result from insults to one or more element(s) in the system (e.g., myelin, axon, soma, synapse, or glia)...

journal_title：Toxicologic pathology

authors： Arezzo JC,Litwak MS,Zotova EG

更新日期：2011-01-01 00:00:00

abstract：:Investigations in toxicologic neuropathology are complex undertakings because of the intricate spatial and temporal diversity in the anatomic, functional, and molecular organization of the central and peripheral nervous systems. This compilation of toxicologic neuropathology resources has been designed to consolidate ...

journal_title：Toxicologic pathology

authors： Bolon B,Bradley A,Garman RH,Krinke GJ

更新日期：2011-01-01 00:00:00

abstract：:A retrospective analysis of microscopic evaluation data from control (device and/or saline-treated) animals in intrathecal studies in monkeys, dogs, sheep, and rats was conducted. The studies were performed by multiple testing facilities. All slide preparation and microscopic evaluation were conducted in the laborator...

journal_title：Toxicologic pathology

authors： Butt MT

更新日期：2011-01-01 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

authors： Mondal NK,Roy A,Mukherjee B,Das D,Ray MR

更新日期：2010-12-01 00:00:00

abstract：:Cardiac troponin (cTn) is a sensitive and specific biomarker for assessing cardiac damage and should be utilized in drug safety assessment. Lactate dehydrogenase and creatine kinase isoenzyme analyses have historically been used in pre-clinical toxicity testing to assess cardiac injury, but since these assays are less...

journal_title：Toxicologic pathology

authors： Reagan WJ

更新日期：2010-12-01 00:00:00

abstract：:7,12-Dimethylbenz[a]anthracene (DMBA) presents a pollutant implicated in various toxicological effects. The aim of this experiment was to study the effects of DMBA administration on oxidative stress, histopathological signs, and 18 kDa translocator protein (TSPO) binding characteristics in rat liver. We also studied t...

journal_title：Toxicologic pathology

authors： Dimitrova-Shumkovska J,Veenman L,Ristoski T,Leschiner S,Gavish M

更新日期：2010-10-01 00:00:00

abstract：:Cytoplasmic vacuolation of sensory neurons has been reported to occur within the dorsal root ganglia in studies investigating various neuropathic conditions including the effects of neurotoxic chemicals. In this study, we investigated this lesion in adult (98-119 days old) male Long-Evans rats, after multiple exposure...

journal_title：Toxicologic pathology

authors： Rogers-Cotrone T,Burgess MP,Hancock SH,Hinckley J,Lowe K,Ehrich MF,Jortner BS

更新日期：2010-06-01 00:00:00

abstract：:An eosinophilic substance (ES) is usually observed in the mouse nasal septum. In contrast to textbooks and one report describing ES as amyloid, a previous study by the authors revealed that ES is not amyloid but consists of collagen and an amorphous material. Furthermore, it was suggested that the amorphous material w...

journal_title：Toxicologic pathology

authors： Doi T,Kokoshima H,Kanno T,Sato J,Wako Y,Tsuchitani M,Matsui T

更新日期：2010-06-01 00:00:00

abstract：:This report describes the findings of preclinical testing of SCH 351591, a selective phosphodiesterase 4 inhibitor, in CD-1 mice over a wide range of doses, in which the heart and reproductive organs of both sexes demonstrated toxic effects. Repeat-dose toxicity studies assessed 5, 15, 50, 100, 200, 400, and 800 mg/kg...

journal_title：Toxicologic pathology

authors： Losco PE,Poulet FM,Kaminska-McNamara GZ,Klein MF

更新日期：2010-06-01 00:00:00

abstract：:BMS-645737, an inhibitor of vascular endothelial growth factor (VEGF) receptor-2 and fibroblast growth factor (FGF) receptor-1, has anti-angiogenic activity and was evaluated in nonclinical studies as a treatment for cancer. This article characterizes the BMS-645737-induced clinical, gross, and histologic lesions of i...

journal_title：Toxicologic pathology

authors： Fletcher AM,Bregman CL,Woicke J,Salcedo TW,Zidell RH,Janke HE,Fang H,Janusz WJ,Schulze GE,Mense MG

更新日期：2010-02-01 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

authors： Hickling KC,Hitchcock JM,Oreffo V,Mally A,Hammond TG,Evans JG,Chipman JK

更新日期：2010-02-01 00:00:00

abstract：:The cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appea...

journal_title：Toxicologic pathology

authors： Cheng L,Ramesh AV,Flesken-Nikitin A,Choi J,Nikitin AY

更新日期：2010-01-01 00:00:00

abstract：:Determining the carcinogenic potential of materials to which humans have significant exposures is an important, complex, and imperfect exercise. Not only are the methods for such determinations protracted and expensive and use large numbers of animals, extrapolation of data from such studies to human risk is imprecise...

journal_title：Toxicologic pathology

authors： Jacobson-Kram D

更新日期：2010-01-01 00:00:00

abstract：:Colorectal cancer, responsible for 50,000 deaths per year, is a contributing factor for considerable mortalities in the United States. Consumption of well-done red meat and saturated fats rich in polycyclic aromatic hydrocarbons may be one of the causative factors for sporadic colon cancer. The objective of this study...

journal_title：Toxicologic pathology

authors： Harris DL,Washington MK,Hood DB,Roberts LJ 2nd,Ramesh A

更新日期：2009-12-01 00:00:00

abstract：:Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but ...

journal_title：Toxicologic pathology

authors： Sano T,Ozaki K,Kodama Y,Matsuura T,Narama I

更新日期：2009-10-01 00:00:00

abstract：:The new Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, which gives guidelines for accommodation and care of animals and was approved on June 15, 2006, was the main reason the authors decided to investigate the origins of the regulatio...

journal_title：Toxicologic pathology

authors： Atalić B,Fatović-Ferencić S

更新日期：2009-10-01 00:00:00

abstract：:The outcome of cardiac ischemic events depends not only on the extent and duration of the ischemic stimulus but also on the myocardial intrinsic tolerance to ischemic injury. Cardiac ischemic tolerance reflects myocardial functional reserves that are not always used when the tissue is appropriately oxygenated. Ischemi...

journal_title：Toxicologic pathology

authors： Golomb E,Nyska A,Schwalb H

更新日期：2009-08-01 00:00:00