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/day, orally by gavage, for one or three months. Findings included higher testes and ovary weights and lower uterus weights (> or =200 mg/kg), small ovaries/uterus (> or =400 mg/kg), and histopathologic changes of large corpora lutea and ovarian atrophy at 200 and 800 mg/kg, respectively. In addition, chronic myocardial inflammation of the heart base occurred at 100 mg/kg. Vaginal staging of the estrous cycle revealed persistent diestrus. There was no histopathologic correlate or morphometric change to explain higher testes weights. A pilot fertility and early embryonic developmental toxicity study assessing doses of 100, 200, 400, and 800 mg/kg/day produced complementary results. Females had prolonged or abnormal estrous cycles, fewer successful pregnancies, increased ovarian corpora lutea, and decreased size of live litters owing to fetal resorptions. Male fertility was not affected. However, males had a 25% increase in testes weights at all doses. The pharmacology of specific PDE4 isoenzymes may explain both the reproductive and cardiac findings.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Losco PE,Poulet FM,Kaminska-McNamara GZ,Klein MFdoi
10.1177/0192623310370463subject
Has Abstractpub_date
2010-06-01 00:00:00pages
568-82issue
4eissn
0192-6233issn
1533-1601pii
0192623310370463journal_volume
38pub_type
杂志文章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：:Quinolone antibacterial agents have adverse effects on the musculoskeletal system in humans, consisting mainly of myalgia and arthralgia, and additionally of tendon disorders and rhabdomyolysis. The present study was conducted to examine the toxic effects of quinolones on the musculoskeletal system in juvenile rats us...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339702500615
更新日期：1997-11-01 00:00:00
abstract：:The fate of inspired mercury vapour (Hg0) is critical in the central nervous system (CNS) where it can circumvent the blood-brain barrier (BBB) at the neuromuscular junction (NMJ) and accumulate indefinitely in motor neurons by retrograde transport. The detoxification of systemic Hg0 by lung and liver requires investi...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230390226069
更新日期：2003-09-01 00:00:00
abstract：:Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five, or eight weeks. At five and eight...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623308323919
更新日期：2008-10-01 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：:Oxidant generation catalyzed by metals has been postulated to account for a lung injury following exposure to air pollution particles. In particles that are predominantly carbonaceous, it is difficult to implicate such an oxidative stress as the responsible mechanism, since concentrations of metals can be extremely lo...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262330002800416
更新日期：2000-07-01 00:00:00
abstract：:Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to deter...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623312464122
更新日期：2013-01-01 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：:Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (5...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339802600318
更新日期：1998-05-01 00:00:00
abstract：:A semiautomated quantitative assay for rat serum alkaline phosphatase (ALP) isoenzyme determination was developed, incorporating selective precipitation of bone alkaline phosphatase (BALP) with wheat germ lectin and differential inhibition with levamisole for determination of intestinal alkaline phosphatase (IALP). Th...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339402200607
更新日期：1994-11-01 00:00:00
abstract：:To clarify the cell of origin of granular cell tumors in the rat brain, light and/or electron microscopic examinations were performed on 40 cases of spontaneous meningeal tumors in Wistar (Jcl: Wistar) rats. The meningeal tumors were histologically subclassified into 3 types: meningothelial meningiomas (MMs), 3 cases;...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339702500211
更新日期：1997-03-01 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
pub_type： 杂志文章
doi：10.1177/0192623311406936
更新日期：2011-06-01 00:00:00
abstract：:Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining l...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623313486316
更新日期：2014-01-01 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
pub_type： 杂志文章
doi：10.1177/0192623312443322
更新日期：2012-10-01 00:00:00
abstract：:Many new observations have been made correlating changes in renal morphology with changes in renal function. These changes have led to a better definition of the various segments which make up the renal tubule. These morphological patterns vary in different species as is documented by morphologic studies and by differ...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262338601400103
更新日期：1986-01-01 00:00:00
abstract：:Perfluorooctanoic acid (PFOA) is a chemical used in the production of fluoropolymers. Its persistence in the environment and presence in humans and wildlife has raised health concerns. Liver tumor induction by PFOA is thought to be mediated in rodents by PPAR-alpha. A recent US EPA scientific advisory board questioned...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623308318216
更新日期：2008-06-01 00:00:00
abstract：:Nephrotoxicity is one of the more common causes of attrition in nonclinical drug development. Like most tissues, the kidney has a limited number of ways of responding to toxicological insults from diverse mechanistic pathways, which can limit the ability to determine mechanisms of renal injury using the assays routine...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623318788302
更新日期：2018-08-01 00:00:00
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：:Exposed to a diverse array of potentially noxious agents, the respiratory tract is protected by a highly developed innate defense system. Physiologically regulated epithelial ion and water transport coordinated with mucin secretion, beating cilia, and cough results in continuous flow of fluid and mucus over airway sur...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1080/01926230601060025
更新日期：2007-01-01 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：:Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern i...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339702500605
更新日期：1997-11-01 00:00:00
abstract：:Parenteral administration of recombinant hematopoietic growth factors has been sporadically associated with cutaneous complications, including injection site reactions in humans and nonhuman primates. In this study, subcutaneous injection sites were evaluated from 12 cynomolgus monkeys administered a recombinant human...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339602400401
更新日期：1996-07-01 00:00:00
abstract：:The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male an...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230252929909
更新日期：2002-05-01 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：: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
pub_type： 杂志文章
doi：10.1177/0192623310379137
更新日期：2010-10-01 00:00:00
abstract：:Minoxidil, a long-acting vasodilating antihypertensive agent, reduces arterial blood pressure by a direct action on arteriolar smooth muscle. The present studies examined the gross anatomic, histologic and ultrastructural myocardial alterations produced by 2 daily doses of minoxidil in beagle dogs (0.5, 1, or 3 mg/kg)...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338901700114
更新日期：1989-01-01 00:00:00
abstract：:Dysfunction of the visual system remains a leading cause of human disability worldwide. Preclinical studies are a key component of efforts to develop drugs and devices to ameliorate visual impairment. Although new opportunities for the delivery of targeted ocular therapeutics have been created, clinical success has be...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623320986558
更新日期：2021-01-05 00:00:00
abstract：:Bioabsorbable implants can be advantageous for certain surgical tissue bioengineering applications and implant-assisted tissue repair. They offer the obvious benefits of nonpermanence and eventual restoration of the native tissue's biomechanical and immunological properties, while providing a structural scaffold for h...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/0192623318816681
更新日期：2019-04-01 00:00:00
abstract：:Absorbable metallic implants have been under investigation for more than a century. Animal and human studies have shown that magnesium (Mg) alloys can be safely used in bioresorbable scaffolds. Several cardiovascular and orthopedic biodegradable metallic devices have recently been approved for use in humans. Bioresorb...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/0192623318816936
更新日期：2019-04-01 00:00:00
abstract：:In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demons...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230390183689
更新日期：2003-03-01 00:00:00
