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, 25, 50, 100, and 200 mg/kg for 2 wk. In addition, 3 groups of 6 male Wistar rats were administered TIPP (PD 114877 and PD 117498, acid hydrolysis products of TIPP) at 100 mg/kg by gavage for 5 days. All animals given 200 mg/kg were euthanatized in moribund condition or found dead after 1 wk of treatment. Clinical evidence of renal toxicity was noted and included emaciation, hematuria, urinary incontinence, and enlarged kidneys at doses of 10 mg/kg and higher. Plasma urea levels were higher than those of controls in all TIPP-treated groups. Significant pathologic changes of the urothelium were evident at all doses and were characterized by necrotizing pyelitis and cystitis. Necrosis and inflammation of the urothelium resulted in secondary hydronephrosis. No renal toxicity was noted with the acid hydrolysis products. The urothelial changes with oral administration of TIPP in rats is species-specific, and the specificity may be related to the metabolism and excretion of the drug.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Macallum GE,Albassam MAdoi
10.1177/019262339402200106subject
Has Abstractpub_date
1994-01-01 00:00:00pages
39-47issue
1eissn
0192-6233issn
1533-1601journal_volume
22pub_type
杂志文章abstract：:A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular d...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623316630836
更新日期：2016-07-01 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：:The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This arti...
journal_title：Toxicologic pathology
pub_type：
doi：10.1177/0192623318800734
更新日期：2018-12-01 00:00:00
abstract：:Toxic injury occurs in the liver more often than any other organ. This can be attributed to the fact that virtually all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances. Drug-induced liver injury has become a ...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1080/01926230590522428
更新日期：2005-01-01 00:00:00
abstract：:Vaginal exfoliative cytology is commonly used in biomedical and toxicological research to classify the stages of the rodent estrous cycle. However, mouse vaginal exfoliative cytology is commonly used as a stand-alone tool and has not been evaluated in reference to vaginal histology and serum sex hormone levels. In thi...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623314526321
更新日期：2014-12-01 00:00:00
abstract：:Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and to fulfill general regulatory requirements for the registration of new drugs, pesticides, or chemicals. Despite significant efforts, the results of inhalation studies have t...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262330002800514
更新日期：2000-09-01 00:00:00
abstract：:The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascu...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623314559103
更新日期：2015-06-01 00:00:00
abstract：:Complete evaluation of the toxicity of a new chemical entity requires critical analysis of the pattern of positive and negative findings in all types of toxicity tests, pharmacokinetics and metabolism in the species examined, and correlation of the effects with information about its pharmacodynamic and pharmacological...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339402200216
更新日期：1994-03-01 00:00:00
abstract：:Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting fr...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262338801600213
更新日期：1988-01-01 00:00:00
abstract：:Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of or...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262339702500109
更新日期：1997-01-01 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
pub_type： 杂志文章
doi：10.1177/0192623311431945
更新日期：2012-04-01 00:00:00
abstract：:Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1080/01926230490425021
更新日期：2004-03-01 00:00:00
abstract：:Sections of thymus from New Zealand white rabbits used as controls in 28-day and 91-day percutaneous toxicity studies conducted at different laboratories were morphometrically assessed. Measurements of total thymic area, medullary area, and cortical area were greater for 28-day vs 91-day studies conducted at a given l...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339001800307
更新日期：1990-01-01 00:00:00
abstract：:The coronavirus disease 2019 pandemic has affected business on numerous fronts in unprecedented and abrupt ways. From site closures and local "stay-at-home orders" to travel advisories and restrictions, the day-to-day practice of toxicologic pathology has been impacted dramatically and rapidly. A critical function of ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623320964087
更新日期：2020-12-01 00:00:00
abstract：:Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623314526006
更新日期：2014-06-01 00:00:00
abstract：:The chloracetanilide herbicide alachlor (2-chloro-2',6-diethyl-N-(methoxymethyl)-acetanilide) induces nasal neoplasms in rats following chronic dietary exposure. The present study sought to identify the cellular origin and mechanisms of tumor induction and progression. Male Long-Evans rats were fed alachlor (0 or 126 ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262330002800602
更新日期：2000-11-01 00:00:00
abstract：:Our previous studies showed that protein kinase Cepsilon (PKCepsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma forma...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230701748164
更新日期：2007-12-01 00:00:00
abstract：:The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 we...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339202000206
更新日期：1992-01-01 00:00:00
abstract：:The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the ne...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262338901700216
更新日期：1989-01-01 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
pub_type： 历史文章
doi：10.1177/0192623311427710
更新日期：2012-01-01 00:00:00
abstract：:To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifications and deletions. Comparison of DNAs from tumor against those from corres...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/019262301317052503
更新日期：2001-03-01 00:00:00
abstract：:We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benig...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230290105668
更新日期：2002-07-01 00:00:00
abstract：:The first part of this paper focuses on the secondary immunodeficiencies caused by immunosuppressive drugs and environmental chemicals. The mechanism of action and the therapeutic effects of azathioprine, glucocorticosteroids, cyclophosphamide, cyclosporin A, and anticancer drugs will be discussed. The immunotoxic act...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262338701500310
更新日期：1987-01-01 00:00:00
abstract：:Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two week...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623308320802
更新日期：2008-07-01 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：:After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and b...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623320917970
更新日期：2020-06-01 00:00:00
abstract：:Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when only dozens of drugs were first described. By the end of the 16th century, the number of drugs documented had reached close to 1,900. And by the end of the last century, published records of CMM have reached 12,800 drugs. The recorded tra...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
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更新日期：2006-01-01 00:00:00
abstract：:At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in ...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262339802600605
更新日期：1998-11-01 00:00:00
abstract：:Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean +/- SEM ages: 149 +/- 13 days) before and after in...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262330002800212
更新日期：2000-03-01 00:00:00
abstract：:Chronic prostatitis characterized on light microscopic examination by moderate, multifocal, predominantly lymphocytic inflammation associated with epithelial atypia and intranuclear and cytoplasmic inclusion-like material was identified in the prostate gland of 2 Wistar Han rats administered an immunomodulatory test a...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623317713320
更新日期：2017-07-01 00:00:00
