Abstract:
:Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Calderón-Garcidueñas L,Mora-Tiscareño A,Gómez-Garza G,Carrasco-Portugal Mdel C,Pérez-Guillé B,Flores-Murrieta FJ,Pérez-Guillé G,Osnaya N,Juárez-Olguín H,Monroy ME,Monroy S,González-Maciel A,Reynoso-Robles R,Villarreal-Calderondoi
10.1177/0192623309340277subject
Has Abstractpub_date
2009-08-01 00:00:00pages
644-60issue
5eissn
0192-6233issn
1533-1601pii
37/5/644journal_volume
37pub_type
杂志文章abstract::The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623316642527
更新日期:2016-08-01 00:00:00
abstract::Studies of xenobiotic biotransformation by in vitro techniques are destined to play an increasingly important role in assessing the safety and efficacy of drugs and other new chemical entities. The first part of this article summarizes some of the in vitro techniques that have been developed to evaluate xenobiotics as...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:
更新日期:1996-01-01 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
pub_type: 杂志文章
doi:10.1177/0192623310385142
更新日期:2011-01-01 00:00:00
abstract::The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their me...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600865523
更新日期:2006-01-01 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::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::In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600695474
更新日期:2006-01-01 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::One of the major roles for the toxicologic pathologists now and into the future will be to determine the biologic significance of chemically induced biochemical and molecular alterations detected in whole tissue homogenates or cell cultures. The biologically significant effects will then require further analysis to de...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301301418973
更新日期:2001-01-01 00:00:00
abstract::Phosphatidylinositol 3-kinases (PI3Ks) regulate intracellular signaling events for multiple cell surface receptors. Phosphatidylinositol 3-kinase δ, 1 of 4 class I PI3K isoforms, is primarily found in leukocytes and regulates immune cell functions. Here, we report changes in the immune and digestive systems that were ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320966238
更新日期:2020-12-01 00:00:00
abstract::Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we hav...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400211
更新日期:1986-01-01 00:00:00
abstract::Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epit...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318779326
更新日期:2018-07-01 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::Weber, K. (2017). Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats. J Toxicol Pathol45, 64-75. (Original DOI: 10.1177/0192623316672075) In the January 2017 issue of Toxicologic Pathology, a number of in text Table citations were incorrectly labeled. The following are the sentences ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,已发布勘误
doi:10.1177/0192623317702643
更新日期:2017-04-01 00:00:00
abstract::The identification, recording, and interpretation of nasal lesions can be a difficult task in toxicology studies. The objective of this article is to provide some guidelines for approaches to nasal toxicologic pathology, based on the author's experience and information available in the published literature. Identifica...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623391019004-103
更新日期:1991-01-01 00:00:00
abstract::Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490261348
更新日期:2004-01-01 00:00:00
abstract::Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, oxymetholone is an ideal candidate for prospective exami...
journal_title:Toxicologic pathology
pub_type: 评论,杂志文章
doi:10.1177/019262339902700503
更新日期:1999-09-01 00:00:00
abstract::Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390241855
更新日期:2003-11-01 00:00:00
abstract::Whole mount enzyme histochemistry to localize lacZ-bearing transgenes (lacZ-WMH) also detects endogenous beta-galactosidases. The experiments reported here evaluated lacZ-WMH as a potential tool for transgene expression analysis during high-throughput rodent necropsies. A lacZ-WMH survey of organs from adult, wild-typ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623307312693
更新日期:2008-02-01 00:00:00
abstract::Renal tubular hyaline droplets developed in male and female F344 rats bearing a rat fibrosarcoma-derived transplantable tumor (SS). The droplets accumulated exclusively in the proximal renal tubular epithelia as eosinophilic granules of various sizes in hematoxylin and eosin-stained sections. The granules stained brig...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600517
更新日期:1998-09-01 00:00:00
abstract::To characterize the hepatic lesions in Fischer 344 (F344) rats afflicted with large granular lymphocyte (LGL) leukemia, the livers of rats with LGL leukemia at various stages were examined histopathologically and immunohistochemically. The morphologic features in the livers of rats afflicted with LGL leukemia were dif...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315578719
更新日期:2015-08-01 00:00:00
abstract::The 2015 Annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to p...
journal_title:Toxicologic pathology
pub_type:
doi:10.1177/0192623316631844
更新日期:2016-06-01 00:00:00
abstract::Morphologic lesions have received only limited attention as in vitro endpoints of toxicity. In the present work, "tissue" and cell morphology of control and toxicant-treated primary dissociated cerebrocortical cell cultures from fetal mice were examined using phase-contrast and bright-field microscopy. In untreated co...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100506
更新日期:1993-09-01 00:00:00
abstract::Osteogenic Protein-1 (OP-1) is a bone morphogen involved in tissue repair and development. We have shown that OP-1 is downregulated during acute ischemic renal injury. Here we report the use of the rat remnant kidney model (RRKM) to evaluate changes in kidney OP-1 expression during chronic injury, and determine if tre...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490440925
更新日期:2004-07-01 00:00:00
abstract::Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and s...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314555162
更新日期:2015-01-01 00:00:00
abstract::Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. A...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400101
更新日期:1986-01-01 00:00:00
abstract::Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory clic...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318816295
更新日期:2019-02-01 00:00:00
abstract::Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932448
更新日期:2006-01-01 00:00:00
abstract::The use of minipigs in preclinical safety testing of pharmaceuticals is considered an alternative to the more traditional dog and nonhuman primate (NHP) nonrodent species. Substantial evidence exists to suggest that the anatomy, physiology, and biochemistry of minipigs are similar enough to humans to consider them as ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315617562
更新日期:2016-04-01 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
pub_type: 杂志文章
doi:10.1177/0192623311413790
更新日期:2011-08-01 00:00:00