Abstract:
:Brain changes associated with risperidone, a dopamine-2/serotonin-2 receptor antagonist, have been documented in rats and humans, but not in nonhuman primates. This study characterized brain changes associated with risperidone in nonhuman primates. Rhesus monkeys were orally administered risperidone in a dose-escalation paradigm up to a maximum tolerated dose of 0.5 mg/kg/day for 3 weeks, or 3 months followed by a 3-month recovery period. Transient and fully reversible neurological signs consistent with risperidone pharmacology were observed. The results of a magnetic resonance imaging evaluation after 3 months of treatment and at the end of the 3-month recovery period showed no meaningful changes in the brain. There were no risperidone-related brain weight changes or gross findings. Histomorphological evaluation of brain sections stained with hematoxylin and eosin, ionized calcium binding adaptor molecule 1 (Iba1), and luxol fast blue/cresyl violet double staining showed no notable differences between control and risperidone groups. However, evaluation of the brain after glial fibrillary acidic protein (GFAP) immunohistochemical staining revealed increased staining in the cell bodies and processes of astrocytes in the putamen without apparent alterations in numbers or distribution. The increase in GFAP staining was present after 3 weeks and 3 months of treatment, but no increase in staining was observed after the 3-month recovery period, demonstrating the reversibility of this finding. The reversible increase in GFAP expression was likely an adaptive, non-adverse response of astrocytes, associated with the pharmacology of risperidone. These observations are valuable considerations in the nonclinical risk assessment of new drug candidates for psychiatric disorders.
journal_name
J Toxicol Patholjournal_title
Journal of toxicologic pathologyauthors
Fernandez G,Kuruvilla S,Hines CDG,Poignant F,Marr J,Forest T,Briscoe Rdoi
10.1293/tox.2019-0004subject
Has Abstractpub_date
2019-10-01 00:00:00pages
233-243issue
4eissn
0914-9198issn
1881-915Xpii
2019-0004journal_volume
32pub_type
杂志文章abstract::A subchronic feeding study of l-serine (l-Ser) was conducted with groups of 10 male and 10 female Fischer 344 rats fed a powder diet containing 0, 0.06, 0.5, 1.5 or 5.0% concentrations of l-Ser for 90 days. There were no toxicologically significant, treatment-related changes with regards to body weight, food intake, w...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.23.39
更新日期:2010-03-01 00:00:00
abstract::The term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. It is rare in cynomolgus macaques (Macaca fascicularis). Here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. Macroscopically, the interventricular septum (IVS) and the...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.2017-0027
更新日期:2018-01-01 00:00:00
abstract::Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4....
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2017-0025
更新日期:2017-10-01 00:00:00
abstract::Sarcopenia is the age-related decrease of muscle mass and function. Diabetes and obesity are known to be risk factors that exacerbate sarcopenia, but the underlying mechanism of diabetes-related sarcopenia is still unknown. Obese type 2 diabetes SDT fatty rats show early onset of severe diabetes and there have been no...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2017-0064
更新日期:2018-04-01 00:00:00
abstract::Polyhexamethylene guanidine hydrochloride (PHMG-HCl), an antimicrobial additive in humidifier disinfectants, was associated with the pulmonary disease outbreak in South Korea. However, PHMG-mediated oxidative stress has only been studied in vitro. Here, we evaluated PHMG-induced oxidative stress in the lungs of rats e...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2019-0049
更新日期:2019-10-01 00:00:00
abstract::The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in t...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2013-0012
更新日期:2013-12-01 00:00:00
abstract::Many variables may affect the outcome of continuous infusion studies. The results largely depend on the experience of the laboratory performing these studies, the technical equipment used, the choice of blood vessels and hence the surgical technique as well the quality of pathological evaluation. The latter is of majo...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.113
更新日期:2011-06-01 00:00:00
abstract::The present report describes a rare case of spontaneous hemangiosarcoma in a nine-week-old male Sprague-Dawley rat. At necropsy, multiple white nodules of various sizes were observed on and within the enlarged spleen and liver and were histopathologically determined to be composed of spindle- to oval-shaped cells that...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.25.273
更新日期:2012-12-01 00:00:00
abstract::Benzo[a]pyrene (BP) is mutagenic but noncarcinogenic in the murine colon. Recently, we reported rapid induction of colonic tumors by treatment of CD2F1 mice with BP (125 mg/kg for 5 days) followed by a colitis inducer, dextran sulfate sodium (DSS) (4% in drinking water for 1 or 2 weeks). However, there are no reports ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2014-0061
更新日期:2015-04-01 00:00:00
abstract::Endometrial adenocarcinoma in the uterine corpus is a malignant cancer that occurs in menopausal women and aged rodents. Because of the similarities in pathogenesis and morphology of endometrial adenocarcinoma in rodents and humans, prediction of the modes of action (MOA) in uterine carcinogenesis is important for ext...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2015-0026
更新日期:2015-10-01 00:00:00
abstract::Extraskeletal osteosarcoma is extremely rare in mice. This case report demonstrates a spontaneous murine extraskeletal osteosarcoma that exhibited various histological growth patterns in an ICR mouse. At necropsy, the tumor mass was located in the abdominal wall and was 45 × 30 × 25 mm in size. Histopathologically, th...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.2015-0046
更新日期:2016-01-01 00:00:00
abstract::Diabetes mellitus (DM) and obesity are believed to be risk factors for colorectal cancer in humans. In experiment 1, male nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model animal of type 2 DM, were whole-body X-irradiated (4 Gy) at 6 and 8 weeks of age and ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.187
更新日期:2011-12-01 00:00:00
abstract::Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents pl...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.9
更新日期:2011-03-01 00:00:00
abstract::We performed a medaka bioassay for the carcinogenicity of methylazoxymethaol acetate (MAM-Ac) to examine the sequential histological changes in the liver from 3 days after exposure until tumor development. The medaka were exposed to MAM-Ac at a concentration of 2 ppm for 24 hours, and were necropsied at 3, 7, 10, 14, ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2020-0033
更新日期:2020-10-01 00:00:00
abstract::The involvement of the lung during the septic systemic inflammatory response elicited by administration of lipopolysaccharide (LPS) was investigated. Eight-week-old male Sprague-Dawley rats were injected i.p. with 15 mg/kg LPS. After 24 h, the lungs were excised to evaluate the cellular responses to LPS. Matrix-assist...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2014-0053
更新日期:2015-01-01 00:00:00
abstract::Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristic...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2016-0035
更新日期:2017-01-01 00:00:00
abstract::Tumor research has largely relied on xenograft models created by the engraftment of cultured cell lines derived from tumor tissues into immunodeficient mice for in vivo studies. Like in vitro models, such models retain the ability of tumor cells to continuously proliferate, so they have been used to predict the clinic...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.2020-0007
更新日期:2020-07-01 00:00:00
abstract::The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internatio...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.31.1S
更新日期:2018-01-01 00:00:00
abstract::To prevent fixation defects or artifacts in the whole bodies of fish caused by conventional fixatives, such as formalin solution, Bouin's fluid (BF), and Davidson's fluid (DF), the optimal fixatives and fixing method were examined. An improved method of fixing the whole bodies of fish was examined that makes use of a ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2018-0001
更新日期:2018-07-01 00:00:00
abstract::The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.23.171
更新日期:2010-09-01 00:00:00
abstract::Liposomes have been used as a vehicle for encapsulating chemicals or toxins in toxicological studies. We investigated the transient effects of empty liposomes on hepatic macrophages by applying a single intravenous injection at a dose of 10 ml/kg body weight in 6-week-old male F344 rats. One day after injection, the n...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2015-0082
更新日期:2016-04-01 00:00:00
abstract::Endogenous prostaglandin (PG) E(2) plays important roles in renal homeostasis. Immunoexpressions of PGE(2) biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE(2) synthetase (mPGES)-1 and EP4 (a PGE(2) receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on ge...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.257
更新日期:2011-12-01 00:00:00
abstract::Dysferlin (DYSF) is involved in the membrane-repair process, in the intracellular vesicle system and in T-tubule development in skeletal muscle. It interacts with mitsugumin 53, annexins, caveolin-3, AHNAK, affixin, S100A10, calpain-3, tubulin and dihydropyridine receptor. Limb-girdle muscular dystrophy 2B (LGMD2B) an...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.25.135
更新日期:2012-06-01 00:00:00
abstract::The common marmoset (Callithrix jacchus) is now widely used in various research fields, including toxicology. However, information about the background pathology of this species is scarce. Here, we report a case of rhabdomyosarcoma that spontaneously occurred in a common marmoset. A 44-month-old male common marmoset w...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.26.187
更新日期:2013-06-01 00:00:00
abstract::We investigated chronological changes in immunohistochemical phenotyping in the thymus and spleen in Crl:CD rats up to the age of about one year. In the thymus, T cells increased markedly from 3 to 4 weeks of age. Proliferating cells also increased markedly at these points. B cells tended towards an increase with age....
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.25.55
更新日期:2012-03-01 00:00:00
abstract::Uterine deciduomas were found in two female virgin rats, a 15-week-old Lewis rat and a 7-week-old Sprague-Dawley rat. The firm white nodules were located at the base of unilateral uterine horns and were approximately 6 mm and 4 mm in diameter. Histopathologically, the nodules were composed of three areas, each with a ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.26.61
更新日期:2013-03-01 00:00:00
abstract::Cardiac hypertrophy was observed in a 9-week-old Crl:CD(SD) rat that died unexpectedly. The animal was allocated to the control group of a toxicity study, and no abnormalities in its general conditions, body weight or food intake were observed. Necropsy revealed an increase in heart weight. Gross examination indicated...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.22.83
更新日期:2009-03-01 00:00:00
abstract::It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the e...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2018-0009
更新日期:2018-10-01 00:00:00
abstract::Accurate analysis of female reproductive toxicity requires a thorough understanding the differences in and specifics of estrous or menstrual cycles between laboratory animals. There are some species differences such as the time of sex maturation, the length of the estrous or menstrual cycle, the length of the luteal p...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.2016-0021
更新日期:2016-07-01 00:00:00
abstract::Morphological and immunohistochemical examinations were carried out on the pancreas of a hyperglycemic 5-year-old male cynomolgus monkey. Body weight gradually decreased from 6 months before termination, accompanying a slight reduction in food consumption and anorexia for the last 2 days. The blood glucose level was m...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.25.215
更新日期:2012-09-01 00:00:00