MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Toxicologic Pathology' source. Sun, 21 Mar 2010 15:54:05 +0100 http://www.medworm.com/index.php?rid=3378358&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231548%26dopt%3DAbstract Authors: Hickling KC, Hitchcock JM, Chipman JK, Hammond TG, Evans JG Cholangiofibrosis is a structural anomaly that precedes the development of cholangiocarcinoma in some rodent models. In this article, the authors examine the contribution of the epithelial and mesenchymal cells in the pathogenesis of this complex lesion. Furan was administered to rats by gavage in corn oil at 30 mg/kg b.w. (five daily doses per week) and livers were sampled between eight hr to three months. Characteristically the administration of furan caused centrilobular injury, and restoration was accomplished by proliferation of hepatocytes. Some areas of the liver were, however, more severely affected, and here, injury extended into portal and capsular areas, which resulted in a rapid proliferation of ductular c... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378358 Thu, 18 Mar 2010 17:00:02 +0100 3378358 http://www.medworm.com/index.php?rid=3378357&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231549%26dopt%3DAbstract Authors: PMID: 20231549 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378357 Thu, 18 Mar 2010 17:00:02 +0100 3378357 http://www.medworm.com/index.php?rid=3378359&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231546%26dopt%3DAbstract Authors: Aguirre SA, Heyen JR, Collette W, Bobrowski W, Blasi ER The receptor tyrosine kinase receptor (RTK) signaling pathway, mesenchymal-epithelial transition factor (c-Met)/hepatocyte growth factor receptor (HGFR), has been implicated in oncogenesis and is a target of interest in cancer therapy. PF-04254644 is a potent and selective inhibitor of c-Met/HGFR. Wide ligand binding profiling of PF-04254644 revealed a potentially significant interaction with phosphodiesterase (PDE) 3, and follow-up PDE enzyme activity assays confirmed PF-04254644 as a potent inhibitor of PDE3 as well as other PDEs (1, 2, 5, 10, and 11). Clinical observations, laboratory, and echocardiography parameters were recorded in Sprague-Dawley (SD) rats that received PF-04254644 oral dosing for up to seven consecu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378359 Tue, 16 Mar 2010 00:00:00 +0100 3378359 http://www.medworm.com/index.php?rid=3378356&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20233943%26dopt%3DAbstract Authors: Singh BP, Nyska A, Kissling GE, Lieuallen W, Johansson SL, Malarkey DE, Hooth MJ B6C3F1 mice chronically exposed to 3,3',4,4'-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic lesions, including carcinoma of the urinary tract. Groups of fifty male and fifty female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10, and 30 mg/kg five days a week for two years. Control animals received corn oil:acetone (99:1) vehicle. Decreased survival of male mice in the mid-dose group and of male and female mice in the high-dose groups was related mainly to the occurrence of urethral transitional cell (urothelial) carcinoma and resulting urinary obstruction. Increased urethral transitional c... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378356 Tue, 16 Mar 2010 00:00:00 +0100 3378356 http://www.medworm.com/index.php?rid=3378355&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20233944%26dopt%3DAbstract This study was conducted to identify the mechanism of the spongy change in aniline-treated rats. The spongy change in the spinal cord white matter was first detected on day 5 in the histopathologic examination. The incidence and severity of the lesions, especially in the lateral and ventral funiculi of the thoracic spinal cord white matter, increased prominently from day 8 to day 10. In all rats, immunohistochemical staining by anti-2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) occurred along the cytoplasmic boundaries of the normal oligodendroglia. However, mild to moderate anti-CNPase staining extended to the swollen cytoplasm of the oligodendroglia in the aniline-treated rats from day 2 to day 4. In the electron microscopic examination, free ribosomes and rough endoplasmic reti... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378355 Tue, 16 Mar 2010 00:00:00 +0100 3378355 http://www.medworm.com/index.php?rid=3378349&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20233945%26dopt%3DAbstract This study demonstrates that RPA-1 is an excellent marker of RPN that can be used to detect this toxicity in preclinical safety testing. PMID: 20233945 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3378349 Tue, 16 Mar 2010 00:00:00 +0100 3378349 http://www.medworm.com/index.php?rid=3359712&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215581%26dopt%3DAbstract Authors: Cohen SM The two-year rodent bioassay remains the mainstay for carcinogenicity testing, although numerous difficulties have been identified. Fundamentally, a chemical can increase the risk of cancer (1) by damaging DNA directly (DNA reactive) or (2) indirectly by increasing the number of DNA replications (non-DNA reactive). Mechanistic research has identified numerous precursor lesions in the sequence of key events necessary for neoplasia development. Based on these concepts, the author has proposed a short-term (thirteen-week) assay for screening for carcinogenic potential based on a mode of action analysis and on readily available, identifiable preneoplastic changes. A screening assay that detects all potential rodent hepatocarcinogens has been previously identified (Toxicol... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3359712 Tue, 09 Mar 2010 00:00:00 +0100 3359712 http://www.medworm.com/index.php?rid=3359711&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215582%26dopt%3DAbstract Authors: Noorafshan A, Karbalay-Doust S, Valizadeh A, Elham Aliabadi , Mirkhani H Metronidazole (MTZ) has negative effects on sperm analysis and testis structure. Curcumin is the principal curcuminoid found in turmeric and exhibits antitumor, anti-inflammatory, and anti-infectious activities with low toxicity. To evaluate stereological changes of seminiferous germinal epithelium by MTZ and ameliorative effects of curcumin, Balb-c mice were divided into 6 groups. The control, second, third, fourth, fifth, and sixth groups were administrated distilled water, high doses of MTZ (500 mg/kg/day), MTZ (500 mg/kg/day) + 100 mg/kg/d curcumin, therapeutic doses of MTZ (165 mg/kg/day), MTZ (165 mg/kg/day) + 100 mg/kg/day curcumin, and 100 mg/kg/day curcumin, respectively. Testis weight, testis vo... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3359711 Tue, 09 Mar 2010 00:00:00 +0100 3359711 http://www.medworm.com/index.php?rid=3359710&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215583%26dopt%3DAbstract Authors: Carter CA, Misra M A short-term 5-day cigarette smoke exposure study was conducted in Fischer 344 rats to identify smoke-induced lung protein changes. Groups of 10 male and 10 female rats at 5 weeks of age were randomly assigned to one of four exposure groups. Animals received filtered air (control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted Kentucky reference 3R4F cigarette smoke. Nose-only exposures were conducted for 3 hours/day for 5 consecutive days. Mean body weights were significantly reduced only in male rats exposed to 400 mg TPM/m(3). Body weight gains were significantly reduced in 200- and 400-mg TPM/m(3)-exposed males and in all smoke-exposed females compared with controls. Alveolar histiocytosis increased slightly in all smoke exposed-fem... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3359710 Tue, 09 Mar 2010 00:00:00 +0100 3359710 http://www.medworm.com/index.php?rid=3359709&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215584%26dopt%3DAbstract Authors: Floettmann E, Gregory L, Teague J, Myatt J, Hammond C, Poucher SM, Jones HB The preclinical efficacy and safety of GPi921, a glycogen phosphorylase inhibitor, was assessed following twenty-eight days of administration to Zucker Diabetic Fatty (ZDF) rats. The ZDF rat is an animal model of type 2 diabetes mellitus (TTDM) which develops severe hyperglycemia. Inhibition of glycogen phosphorylase throughout the duration of the study was demonstrated by reductions in twenty-four-hour glucose profiles and glycated hemoglobin levels. In addition, progression towards hyperglycemia was halted in treated but not control animals, which developed hyperglycemia over the twenty-eight days of the study. Biochemical and histopathological analysis revealed large increases in hepatic glycogen, w... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3359709 Tue, 09 Mar 2010 00:00:00 +0100 3359709 http://www.medworm.com/index.php?rid=3359708&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215585%26dopt%3DAbstract Authors: Pace V, Wieczorek G, Pace M, Weber K, Perentes E A primary angiosarcoma was found in the tongue of a six-week-old female Wistar rat, sacrificed for humane reasons during the course of a four-week toxicology study. At necropsy, a nodule protruding from the dorsal part of the tongue was found. The nodule displayed microscopically, irregularly shaped vascular spaces separated by collagenous stroma. The spindle-shaped endothelial cells showed pleomorphism, hyperchromatism, and low mitotic activity; large nuclei with one or more nucleoli were present. Multiple metastases were found in the lungs, and the morphology of the cells resembled that of the primary tumor. Immunohistochemically, the primary tumor and the lung metastases were positive for von Willebrand factor and vimentin. T... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3359708 Tue, 09 Mar 2010 00:00:00 +0100 3359708 http://www.medworm.com/index.php?rid=3307602&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176784%26dopt%3DAbstract Authors: PMID: 20176784 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3307602 Fri, 26 Feb 2010 02:52:03 +0100 3307602 http://www.medworm.com/index.php?rid=3307601&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176785%26dopt%3DAbstract Authors: Foster JR PMID: 20176785 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3307601 Fri, 26 Feb 2010 02:52:03 +0100 3307601 http://www.medworm.com/index.php?rid=3307600&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176786%26dopt%3DAbstract Authors: Hawes JJ, Reilly KM Neurofibomatosis (NF1) patients are susceptible to multiple tumors of the nervous system including neurofibromas, optic glioma, malignant peripheral nerve sheath tumors (MPNSTs), and astrocytoma. The Nf1+/-;Trp53+/- (NPcis) mouse model of NF1 spontaneously develops astrocytoma and MPNSTs that are very similar to human NF1 tumors. To use this model for testing potential therapeutics, we have developed systems that take advantage of bioluminescent reporters of tumor growth. We have generated E2F1 promoter-driving luciferase (ELUX) reporter mice to detect proliferating tumors in NPcis mice in vivo using bioluminescence. The power of this system is that it enables looking at tumor evolution and detecting spontaneous tumors at early stages of development as they... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3307600 Fri, 26 Feb 2010 02:52:03 +0100 3307600 http://www.medworm.com/index.php?rid=3307599&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176787%26dopt%3DAbstract Authors: Louden C, Brees D, Reagan W, Reynolds D, York M, Dieterle F PMID: 20176787 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3307599 Fri, 26 Feb 2010 02:52:03 +0100 3307599 http://www.medworm.com/index.php?rid=3240727&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124492%26dopt%3DAbstract Authors: Kodama R, Yang X, Sasaki Y, Iwashige S, Tanigawa Y, Yoshikawa T, Nagaoka T, Kamimura Y, Maeda H Alzheimer's disease (AD) in humans is a progressive neurogenic disease that can be linked with such characteristic pathological findings in the cerebrum as senile plaques (SPs), neurofibrillary tangles (NFTs), cerebral amyloid angiopathy (CAA), and neuronal loss. In the present study, the authors investigated the age-related morphological changes in 12 middle-aged and 12 young cynomolgus monkeys. Low numbers of neurons and astrocytes in the hippocampal region in cynomolgus monkeys accompanied ageing, and there was a high number of microglial cells; however, no clearly neurotoxic abnormalities due to beta-amyloid were noted before the age of 20 years. The onset of SPs and CAA in the ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240727 Tue, 02 Feb 2010 00:00:00 +0100 3240727 http://www.medworm.com/index.php?rid=3240726&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124493%26dopt%3DAbstract Authors: Vidal JD, Drobatz LS, Holliday DF, Geiger LE, Thomas HC The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but the impact of the geographic source of cynomolgus macaque on differences in spontaneous pathology and response to xenobiotics has only recently been explored. Previous work from the authors' facility has described spontaneous cardiac findings in predominantly Indonesian-source animals; however, the authors have recently observed a novel spectrum of cardiac findings in Mauritian-source animals. This review evaluated the spontaneous macroscopic and microscopic cardiac findings in vehicle control Mauritian-source macaques used for routine toxicity testing. When compared to the prior review in predominantly Indonesian macaqu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240726 Tue, 02 Feb 2010 00:00:00 +0100 3240726 http://www.medworm.com/index.php?rid=3240725&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124494%26dopt%3DAbstract Authors: Marty MS, Singh NP, Stebbins KE, Linscombe VA, Passage J, Gollapudi BB If p53 is essential to eliminate damaged spermatogenic cells, then mutagen exposure in the absence of p53 would increase sperm containing damaged DNA. p53 knockout (-/-, NULL) and wild-type (+/+, WT) mice (five/group) were exposed to ethylnitrosourea (ENU) or cyclophosphamide (CP). In phase I, mice were exposed by gavage to 0 or 60 mg/kg/day ENU or CP for four days and examined on test day (TD) 4, and in phase II, mice were exposed to 0, 6, 20, or 60 mg/kg/day ENU or CP for four days and evaluated on TD 36 when exposed spermatocytes matured. In phase I, mutagens were not directly cytotoxic to mature sperm. In phase II, WT mice were more sensitive to decreases in reproductive organ weights, whereas both geno... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240725 Tue, 02 Feb 2010 00:00:00 +0100 3240725 http://www.medworm.com/index.php?rid=3240724&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124495%26dopt%3DAbstract Authors: Long GG PMID: 20124495 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240724 Tue, 02 Feb 2010 00:00:00 +0100 3240724 http://www.medworm.com/index.php?rid=3240723&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124496%26dopt%3DAbstract Authors: Vahle JL PMID: 20124496 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240723 Tue, 02 Feb 2010 00:00:00 +0100 3240723 http://www.medworm.com/index.php?rid=3240722&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124497%26dopt%3DAbstract Authors: Lorentzen RJ PMID: 20124497 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240722 Tue, 02 Feb 2010 00:00:00 +0100 3240722 http://www.medworm.com/index.php?rid=3240721&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124498%26dopt%3DAbstract This article highlights possible ways to gather and present data pertinent to carcinogenesis in man and suggests that it is the toxicological pathology community that should take the lead here in persuading regulators that there is great room for improvement in this particular aspect of regulatory pathology. PMID: 20124498 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240721 Tue, 02 Feb 2010 00:00:00 +0100 3240721 http://www.medworm.com/index.php?rid=3240720&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124499%26dopt%3DAbstract Authors: Nishikawa S, Sano F, Takagi K, Okada M, Sugimoto J, Takagi S Spontaneous salivary gland tumors in rats are rare. The authors report a poorly differentiated carcinoma of a submandibular gland in a ten-week-old rat that was positive for vimentin. Microscopically, the neoplastic cells showed a diffuse growth pattern in most areas of the tumor mass and a nestlike structure in a part of the peripheral area. Immunohistochemically, the cells were positive for keratin and vimentin but not for alpha-smooth muscle actin. Ultrastructurally, desmosome-like structures were observed. Based on these findings, the tumor was diagnosed as a poorly differentiated carcinoma. The origin of the neoplastic cells would be either acinar or ductal cells. This suggests that acinar or ductal cells have t... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240720 Tue, 02 Feb 2010 00:00:00 +0100 3240720 http://www.medworm.com/index.php?rid=3240719&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124500%26dopt%3DAbstract Authors: Hickling KC, Hitchcock JM, Oreffo V, Mally A, Hammond TG, Evans JG, Chipman JK 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 administered via oral gavage (30 mg/kg b.w. 5 daily doses per week), and livers were analyzed at time points between eight hr and three months. A one-month recovery group previously treated for three months was also included. There was a marked association between CYP2E1 expression and DNA oxidation (8-oxo-dG) in areas of centrilobular hepatocyte necrosis seen after a single dose. After o... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240719 Tue, 02 Feb 2010 00:00:00 +0100 3240719 http://www.medworm.com/index.php?rid=3240718&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124501%26dopt%3DAbstract This report is intended to establish a general profile of tumor occurrence in young Han Wistar rats. Data were collected and evaluated from 29 rat carcinogenicity studies and from a few 2-, 4-, 13-, and 26-week studies conducted between 1995 and 2009 at Huntingdon Life Sciences, UK. The route of administration was dietary, oral gavage, or inhalation, and the analysis was confined to sporadic deaths (decedents) in carcinogenicity studies. In Han Wistar rats, the most common and earliest occurring tumor was malignant lymphoma in both sexes, the earliest being seen in the 16th and 26th week in males and females, respectively. The incidence of malignant lymphoma was slightly higher in males than in females. The second most common type of tumor was brain tumors in males and mammary tumors in fe... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3240718 Tue, 02 Feb 2010 00:00:00 +0100 3240718 http://www.medworm.com/index.php?rid=3217141&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100840%26dopt%3DAbstract This article characterizes the BMS-645737-induced clinical, gross, and histologic lesions of incisor teeth in Sprague-Dawley (SD) rats. Rats received 0 800 mg/kg BMS-645737 in a single-dose study or consecutive daily doses of 0 20 mg/kg/day in a 1-month study. The reversibility of these effects was assessed in the 1-month study. White discoloration and fracture of incisors were observed clinically and grossly in the 1-month study. In both studies, dose-dependent histopathologic lesions of incisors were degeneration and/or necrosis of odontoblasts and ameloblasts; decreased mineralization of dentin; inflammation and necrosis of the dental pulp; and edema, congestion, and hemorrhage in the pulp and periodontal tissue adjacent to the enamel organ. Partial recovery was observed at lower doses ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3217141 Mon, 25 Jan 2010 00:00:00 +0100 3217141 http://www.medworm.com/index.php?rid=3217140&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100841%26dopt%3DAbstract Authors: Brady S, York M, Scudamore C, Williams T, Griffiths W, Turton J aThe current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of isoprotenerol (ISO) and subcutaneous (SC) versus IP routes of administration of ISO on serum cardiac troponin I (cTnI) levels in female Hanover Wistar rats, providing additional evidence to support acceptance of cTnI as a cardiac biomarker. At 2 hr postdosing with 0-500 mug/kg ISO, mean serum cTnI levels were increased in a dose-related fashion at >/=10 mug/kg with no evidence of cardiac pathology. At 24 h, cTnI concentrations were generally at control levels, but histologic cardiomyocyte injury was evident in a proportion of the animals given >/=10 mug/kg. In a second experiment, rats given SC ISO at 5,000 mug/kg ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3217140 Mon, 25 Jan 2010 00:00:00 +0100 3217140 http://www.medworm.com/index.php?rid=3217139&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100842%26dopt%3DAbstract Authors: Madheswaran R, Shelar PD, Kalaiselvan P, Bhelonde JJ, Mathur KY, Pande VV, Udupa V, Shingatgeri VM A male CD-1 mouse from a segment I reproduction toxicity study died at the age of fifteen weeks. At necropsy, the thymus was abnormally enlarged and virtually obliterated the thoracic cavity. Histopathological examination of thymus revealed abundant cell population consisting of mature lymphocytes and few lymphoblasts arranged in cords and sheets. Neoplastic cells completely obliterated the thymic architecture, and loss of corticomedullary junction was evident. Microscopically, neoplastic cells were round with moderate cytoplasm. Nuclei were spherical and hyperchromatic with centrally placed nucleoli. Mitotic figures and tingible body macrophages imparting "starry sky appearance"... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3217139 Mon, 25 Jan 2010 00:00:00 +0100 3217139 http://www.medworm.com/index.php?rid=3217138&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100843%26dopt%3DAbstract This study showed that saline injection did not fundamentally alter the morphology of the injection sites used for the principal study. Skin thickness was greater in males than in females. Although acellular intimal thickening occurred spontaneously in the dorsal skin of untreated males and females, only males had a spontaneous incidence of intimal hyperplasia. No site predilection for intimal lesions was apparent for either sex. Saline injection, or the physical trauma of injection, may induce intimal hyperplasia; males appear more likely to develop the lesion than do females. It is possible that acellular intimal thickening can progress to intimal hyperplasia under appropriate conditions. PMID: 20100843 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3217138 Mon, 25 Jan 2010 00:00:00 +0100 3217138 http://www.medworm.com/index.php?rid=3217137&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100844%26dopt%3DAbstract Authors: Baudimont F, Booler H, Casey T, Heier A Histological examination of the heart of a clinically normal, 10-week-old female Han Wistar rat revealed a 600 x 400-mum mass of ectopic thyroid tissue within the subendothelial connective tissue of the aortic valve. The mass protruded into the left ventricular lumen and was composed of single layers of cuboidal to low-columnar epithelium organized into follicles often containing colloid. Parafollicular cells were not evident. To the authors' knowledge, this is the first report of intracardiac ectopic thyroid gland in the rat and the first report of ectopic thyroid within a heart valve in a mammal. PMID: 20100844 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3217137 Mon, 25 Jan 2010 00:00:00 +0100 3217137 http://www.medworm.com/index.php?rid=3209182&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20097795%26dopt%3DAbstract Authors: Naiki-Ito A, Asamoto M, Naiki T, Ogawa K, Takahashi S, Sato S, Shirai T Acetaminophen (APAP) is a widely used antipyretic and analgesic agent. However, overdosing and sometimes even a recommended dose can lead to serious and conceivably fatal liver toxicity. Therefore, it is important to clarify understand mechanisms of hepatotoxicity induced by APAP. Gap junctions, formed by connexin, have important roles in maintenance of tissue homeostasis and control of cell growth and differentiation. In the liver, Cx32 is a major gap junction protein whose expression is known to gradually decrease with chronic liver disease progression. In the present study, acute hepatotoxic effects of APAP were found to be reduced in Cx32 dominant negative transgenic rats lacking normal gap junctional ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3209182 Fri, 22 Jan 2010 00:00:00 +0100 3209182 http://www.medworm.com/index.php?rid=3185752&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080933%26dopt%3DAbstract Authors: Tsuda H, Futakuchi M, Fukamachi K, Shirai T, Imaida K, Fukushima S, Tatematsu M, Furukawa F, Tamano S, Ito N The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive. The false-positive detection of noncarcinogens was low; a single false-positive result was obtained from the 50 nonc... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3185752 Fri, 15 Jan 2010 00:00:00 +0100 3185752 http://www.medworm.com/index.php?rid=3185751&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20080934%26dopt%3DAbstract Authors: Bennett CN, Green JE Cross-species genomic analyses have proven useful for identifying common genomic alterations that occur in human cancers and mouse models designed to recapitulate human tumor development. High-throughput molecular analyses provide a valuable tool for identifying particular animal models that may represent aspects of specific subtypes of human cancers. Corresponding alterations in gene copy number and expression in tumors from mouse and human suggest that these conserved changes may be mechanistically essential for cancer development and progression, and therefore, they may be critical targets for therapeutic intervention. Using a cross-species analysis approach, mouse models in which the functions of p53, Rb, and BRCA1 have been disrupted demonstrate molec... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3185751 Fri, 15 Jan 2010 00:00:00 +0100 3185751 http://www.medworm.com/index.php?rid=3180472&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20075108%26dopt%3DAbstract Authors: Maziasz T, Kadambi VJ, Silverman L, Fedyk E, Alden CL A daunting, unmet medical need exists for effective oncology chemotherapies, with cancer deaths in 2009 to exceed 560,000 in the United States alone. Because of the rapid demise of the majority of cancer patients with metastatic disease, oncology drug development must follow a much different paradigm than therapeutic candidates for less onerous diseases. The majority of drug candidates in development today are targeted at cancer therapy. Many of these candidate chemotherapeutic agents are active against novel targets, often presenting unique toxicological profiles. Since many of these novel targets are not unique to cancer cells, therapeutic margins may not exist. Decision making, in this event, is among the most challengin... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3180472 Thu, 14 Jan 2010 00:00:00 +0100 3180472 http://www.medworm.com/index.php?rid=3119140&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20028992%26dopt%3DAbstract Authors: Painter JT, Clayton NP, Herbert RA Immunohistochemistry (IHC) has been somewhat underutilized in the practice of toxicological pathology but can be a valuable tool for the evaluation of rodent neoplasms, both in a diagnostic and an investigational role. Determining an exact tumor type using standard hematoxylin and eosin (H&E) staining of formalin-fixed tissues can be challenging, especially with metastatic and/or poorly differentiated tumors. Successful IHC is dependent on many factors, including species and tissue type, type and duration of fixation, quality fresh or frozen sectioning, and antibody specificity. The initial approach of most tumor diagnosis IHC applications is distinguishing epithelial from mesenchymal differentiation using vimentin and cytokeratin markers... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3119140 Tue, 22 Dec 2009 00:00:00 +0100 3119140 http://www.medworm.com/index.php?rid=3102207&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20008546%26dopt%3DAbstract Authors: Popp JA PMID: 20008546 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3102207 Sat, 19 Dec 2009 05:10:03 +0100 3102207 http://www.medworm.com/index.php?rid=3102206&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20008547%26dopt%3DAbstract Authors: Aguirre SA, Huang W, Prasanna G, Jessen B Prostaglandin receptor agonists have intraocular pressure-lowering effects in humans and are of interest in the treatment of glaucoma. The prostanoid receptor agonist PF-04475270 is a potent and selective agonist of the prostaglandin E(2) receptor EP4. This paper characterizes the toxicity associated with topical ocular administration of PF-04475270 in beagles. Dogs were given PF-04475270 topically to the eye on a consecutive daily dosing schedule for one or four weeks followed by a one-or four-week reversal period, respectively. Clinical observations, ophthalmic, and laboratory parameters were recorded. Necropsies were conducted at the end of the dosing and recovery phases, and histologic examinations performed. Corneal neovasculariza... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3102206 Sat, 19 Dec 2009 05:10:03 +0100 3102206 http://www.medworm.com/index.php?rid=3102205&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20008548%26dopt%3DAbstract Authors: Egerod FL, Svendsen JE, Hinley J, Southgate J, Bartels A, Brünner N, Oleksiewicz MB To facilitate studies of the rat bladder carcinogenicity of dual-acting PPAR alpha+gamma agonists, we previously identified the Egr-1 transcription factor as a candidate carcinogenicity biomarker and developed rat models based on coadministration of commercially available specific PPAR alpha and PPAR gamma agonists. Immunohistochemistry for Egr-1 with a rabbit monoclonal antibody demonstrated that male vehicle-treated rats exhibited minimal urothelial expression and specifically, no nuclear signal. In contrast, Egr-1 was induced in the nuclei of bladder, as well as kidney pelvis, urothelia within one day (2 doses) of oral dosing of rats with a combination of 8 mg/kg rosiglitazone and 200 m... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3102205 Sat, 19 Dec 2009 05:10:03 +0100 3102205 http://www.medworm.com/index.php?rid=3102204&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20008549%26dopt%3DAbstract Authors: Chatman LA, Morton D, Johnson TO, Anway SD Drug-induced phospholipidosis (PL) is an excessive accumulation of phospholipids and drug in lysosomes. Phospholipidosis signals a change in cell membrane integrity and accumulation of intracellular drug or metabolite in tissues. The sensitivity and susceptibility of preclinical models to detect PL vary with therapeutic agents, and PL is expected to be reversible after discontinuation of drug treatment. The prevailing scientific opinion is that PL by itself is not adverse; however, some regulatory authorities consider PL to be adverse because a small number of chemicals are able to cause PL and concurrent organ toxicity. Until a greater understanding of PL emerges, a well-thought-out risk management strategy for PL will increase confi... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3102204 Sat, 19 Dec 2009 05:10:03 +0100 3102204 http://www.medworm.com/index.php?rid=3102203&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20008954%26dopt%3DAbstract Authors: Elmore S, Bach U, Hailey J, Hill G, Kaufmann W, Latimer K, Malarkey D, Maronpot R, Miller R, Moore R, Morrison J, Nolte T, Rinke M, Rittinghausen S, Suttie A, Travlos G, Vahle J, Willson G The National Toxicology Program (NTP) Satellite Symposium is a one-day meeting that is held in conjunction with the annual Society of Toxicologic Pathology (STP) meeting. The topic of the 2009 Symposium was "Tumor Pathology and INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Nomenclature." The goal of this article is to provide summaries of each speaker's presentation, including the diagnostic or nomenclature issues that were presented, along with a few select images that were used for voting. The results of the voting process and int... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3102203 Tue, 15 Dec 2009 00:00:00 +0100 3102203 http://www.medworm.com/index.php?rid=3030610&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19933552%26dopt%3DAbstract Authors: Fernandez SV, Russo J There is growing concern that estrogenic environmental compounds that act as endocrine-disrupting chemicals might potentially have adverse effects on hormone-sensitive organs such as the breast. This concern is further fueled by evidence indicating that natural estrogens, specifically 17beta-estradiol, are important factors in the initiation and progression of breast cancer. We have developed an in vitro-in vivo model in which we have demonstrated the carcinogenicity of E2 in human breast epithelial cells MCF-10F. Hypermethylation of NRG1, STXBP6, BMP6, CSS3, SPRY1, and SNIP were found at different progression stages in this model. The use of this powerful and unique model has provided a tool for exploring whether bisphenol A and butyl benzyl phthalate ha... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3030610 Sat, 21 Nov 2009 00:00:00 +0100 3030610 http://www.medworm.com/index.php?rid=3005121&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19920280%26dopt%3DAbstract Authors: Cheng L, Ramesh AV, Flesken-Nikitin A, Choi J, Nikitin AY 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 appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human cancers have been complicated by the use of immunocompromised mice. Genetically defined immunocompetent autochthonous mouse models of human cancer provide a valuable tool to address this problem. Furthermore, they allow for a b... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=3005121 Tue, 17 Nov 2009 00:00:00 +0100 3005121 http://www.medworm.com/index.php?rid=2999900&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19915137%26dopt%3DAbstract Authors: Long GG, Morton D, Peters T, Short B, Skydsgaard M The Carcinogenicity Alternative Mouse Models (CAMM) Working Group of the Society of Toxicologic Pathology (STP) surveyed the membership to define current practices and opinions in industry regarding the use of alternative mouse models for carcinogenicity testing. The results of the survey indicated that CAMM are used most often to fulfill a regulatory requirement (e.g., to replace the two-year mouse bioassay) and are being accepted by regulatory agencies. Alternative models are also sometimes used for internal decision making or to address a mechanistic question. The CAMM most commonly used are the p53+/- and rasH2. The rasH2 appears to be the currently accepted model for general carcinogenicity testing. Problems with study in... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2999900 Fri, 13 Nov 2009 00:00:00 +0100 2999900 http://www.medworm.com/index.php?rid=2989829&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19907054%26dopt%3DAbstract This article presents concepts and strategies to reduce the attrition of small molecule oncology therapeutic drug candidates due to toxicity. PMID: 19907054 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2989829 Wed, 11 Nov 2009 00:00:00 +0100 2989829 http://www.medworm.com/index.php?rid=2971313&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19893055%26dopt%3DAbstract Authors: Storer RD, Sistare FD, Reddy MV, Degeorge JJ International guidelines allow for use of a short-term cancer bioassay (twenty-six weeks) in transgenic mice as a substitute for one of the two required long-term rodent bioassays in the preclinical safety evaluation of pharmaceuticals. The two models that have gained the widest acceptance by sponsors and regulatory authorities are the CB6F1-RasH2 mouse hemizygous for a human H-ras transgene and the B6.129N5-Trp53 mouse heterozygous for a p53 null allele. The p53(+/-) model is of particular value for compounds with residual concern that genotoxic activity may contribute to tumorigenesis. The rasH2 model is an appropriate alternative without regard to evidence of genotoxic potential. Since results from a short-term bioassay can be ob... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2971313 Thu, 05 Nov 2009 00:00:00 +0100 2971313 http://www.medworm.com/index.php?rid=2965321&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19887650%26dopt%3DAbstract Authors: Jacobson-Kram D 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. With improved understanding of oncogene activation and tumor suppressor gene inactivation, a number of animal models have been developed to dramatically reduce latency for chemically induced cancers and has led to the development and use of shorter carcinogenicity assays. Recent studies by a number of investigators suggest that specific gene signature patterns seen after short-term exposure of rats to test chemicals can predict long-term outcomes... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2965321 Tue, 03 Nov 2009 00:00:00 +0100 2965321 http://www.medworm.com/index.php?rid=2959125&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19884653%26dopt%3DAbstract This article summarizes key points from Dr. Bernard Leblanc's presentation European Perspectives on Alternative Mouse Carcinogenicity Models and a distillation of questions and answers from a panel discussion following presentations on Alternative Mouse Models for Carcinogenicity Assessment at the Society of Toxicologic Pathology's annual symposium on June 23, 2009, in Washington, DC. PMID: 19884653 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2959125 Mon, 02 Nov 2009 00:00:00 +0100 2959125 http://www.medworm.com/index.php?rid=2959126&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19880825%26dopt%3DAbstract Authors: Raber J This review summarizes some of the topics discussed at the 28th Annual Symposium of the Society of Toxicologic Pathology. The symposium was held in Washington, DC, in 2009 and dealt with unintended adverse events associated with cranial irradiation as part of cancer therapy. We will discuss the importance of considering genetic susceptibility and sex differences in susceptibility to develop these adverse events. Further, we will discuss potential mechanisms contributing to these events, including alterations in neurogenesis and increased oxidative stress following irradiation and potential alterations in synaptic and dendritic markers. PMID: 19880825 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2959126 Fri, 30 Oct 2009 00:00:00 +0100 2959126 http://www.medworm.com/index.php?rid=2940201&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19858501%26dopt%3DAbstract Authors: Senior JR Chemotherapy is meant to be toxic, but it is particularly aimed at the tumor cells. Collateral damage may occur to normal cells and tissues, especially if they are fairly rapidly regenerating, as is the case for bone marrow cells, intestinal epithelial cells, and liver cells after hepatic injury. The liver has a great capacity to resist injury, overcome it, and to regenerate, even after quite massive injury (resection of 50%-65%, for example). This capacity may make it susceptible to chemotherapeutic toxicity, and a struggle between injury and adaptation, leading to recovery and tolerance or to failure and death. If the chemotherapy is aimed just at delaying progression of the cancer for a few weeks or months, it may not be worth the risk of irreversible liver injury... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2940201 Mon, 26 Oct 2009 00:00:00 +0100 2940201 http://www.medworm.com/index.php?rid=2931862&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854888%26dopt%3DAbstract In conclusion, the increases in cTnI concentrations six hours after the administration of hydralazine were indicative of a myocardial damage that did not consistently have a microscopic correlate. However, the window of increased cTnI concentrations was short, and only microscopic evaluation of the heart detected the damage at twenty-four to forty-eight hours after the episode of acute myocardial necrosis. PMID: 19854888 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2931862 Fri, 23 Oct 2009 00:00:00 +0100 2931862 http://www.medworm.com/index.php?rid=2923512&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19846892%26dopt%3DAbstract Authors: Hoenerhoff MJ, Hong HH, Ton TV, Lahousse SA, Sills RC Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental car... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2923512 Tue, 20 Oct 2009 23:00:00 +0100 2923512 http://www.medworm.com/index.php?rid=2916667&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19843952%26dopt%3DAbstract Authors: Ward JM Cancer in an important disease throughout the world and a major cause of death in both humans and animals. Pathologists play a critical role in cancer research and in the diagnosis, treatment, and prevention of human and animal cancers. They participate in basic and translational research in laboratories of colleges and universities, other research institutes, government research and regulatory agencies, and in the biotech, chemical, and pharmaceutical industries. This introductory review to the 2009 STP Symposium on Cancer will identify and discuss the major roles of pathologists in cancer research. PMID: 19843952 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2916667 Mon, 19 Oct 2009 23:00:00 +0100 2916667 http://www.medworm.com/index.php?rid=2916666&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19843953%26dopt%3DAbstract Authors: Yoshizawa K, Brix AE, Sells DM, Jokinen MP, Wyde M, Orzech DP, Kissling GE, Walker NJ, Nyska A Results from previously published animal studies suggest that prenatal and postnatal exposure to dioxin and dioxin-like compounds (DLCs) may profoundly affect the reproductive system of both sexes via endocrine disruption. In the present work, we evaluate the toxicity and carcinogenicity of various DLCs, with an emphasis on their effect on the reproductive organs, induced by chronic exposure of female adult Harlan Sprague-Dawley rats. This investigation represents part of an initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For fourteen, thirty-one, or fifty-three ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2916666 Mon, 19 Oct 2009 23:00:00 +0100 2916666 http://www.medworm.com/index.php?rid=2916670&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19841129%26dopt%3DAbstract Authors: Bailey K, Xia Y, Ward WO, Knapp G, Mo J, Mumford JL, Owen RD, Thai SF The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in th... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2916670 Sun, 18 Oct 2009 23:00:00 +0100 2916670 http://www.medworm.com/index.php?rid=2916669&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19841130%26dopt%3DAbstract The objective of this study was to investigate whether the formation of colon tumors in adult Apc(Min) mice was influenced by the ingestion of different types of fat containing benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon compound. Treatment consisted of 50 and 100 microg B(a)P/kg body weight dissolved in peanut or coconut oil (representatives of unsaturated and saturated fats, respectively) administered daily to six-week-old male Apc(Min) mice via oral gavage for sixty days. At the end of exposure, mice were sacrificed; jejunum and colons were retrieved and preserved in 10% formalin for observation for gross pathological changes. An increased prevalence of adenomas in colons of mice that ingested B(a)P through saturated dietary fat compared to unsaturated fat and controls (p ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2916669 Sun, 18 Oct 2009 23:00:00 +0100 2916669 http://www.medworm.com/index.php?rid=2916668&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19841131%26dopt%3DAbstract Conclusion: The choice of specific synthetic progestins has profound implications on the development of kidney injury and renal gene expression under conditions of elevated aldosterone serum levels and salt intake. PMID: 19841131 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2916668 Sun, 18 Oct 2009 23:00:00 +0100 2916668 http://www.medworm.com/index.php?rid=2903228&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19833912%26dopt%3DAbstract Authors: Wei M, Hamoud AS, Yamaguchi T, Kakehashi A, Morimura K, Doi K, Kushida M, Kitano M, Wanibuchi H, Fukushima S As susceptibility to carcinogens varies considerably among different strains of experimental animals, evaluation of dose-response relationships for genotoxic carcinogen in different strains is indispensable for risk assessment. Potassium bromate (KBrO3) is a genotoxic carcinogen inducing kidney cancers at high doses in male F344 rats, but little is known about its carcinogenic effects in other strains of rats. The purpose of the present study was to determine dose-response relationships for carcinogenic effects of KBrO3 on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced kidney carcinogenesis in male Wistar rats. We found that KBrO3 showed significant enhancement effect... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2903228 Wed, 14 Oct 2009 23:00:00 +0100 2903228 http://www.medworm.com/index.php?rid=2903227&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19833913%26dopt%3DAbstract Authors: Cartwright ME, Petruska J, Arezzo J, Frank D, Litwak M, Morrissey RE, Macdonald J, Davis TE The azole antifungal drug posaconazole caused phospholipidosis in neurons of the central nervous system, dorsal root ganglia of the spinal cord, and myenteric plexus in chronic toxicity studies in dogs. The time of onset, light and electron microscopic features, neurologic and electrophysiologic effects on the central and peripheral nervous systems, and potential for regression were investigated in a series of studies with a duration of up to one year. Nuclei of the medulla oblongata were the prominently affected areas of the brain. Neurons contained cytoplasmic vacuoles with concentrically whorled plasma membrane-like material (i.e., multilamellar bodies) morphologically identical to t... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2903227 Wed, 14 Oct 2009 23:00:00 +0100 2903227 http://www.medworm.com/index.php?rid=2884637&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19820139%26dopt%3DAbstract Authors: Bolon B, Ochoa R, Mann P The June 2009 Town Hall meeting of the Society of Toxicologic Pathology (STP) and a subsequent survey considered whether or not STP should endorse a published proposal (Toxicol Pathol 37: 553-561, 2009) by the International Federation of Societies of Toxicologic Pathologists (IFSTP) to provide global recognition by credential review for toxicologic pathologists engaged in regulatory-type, nonclinical toxicology studies. One-third (374 of 1082) of STP members answered the survey. The majority of respondents rejected the IFSTP proposal (55% against) but favored the concept of global recognition (57% for), if available to both anatomic pathologists and clinical pathologists (67% for). Members preferred recognition by credential review (49% for) or via an ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2884637 Thu, 08 Oct 2009 23:00:00 +0100 2884637 http://www.medworm.com/index.php?rid=2869042&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19805614%26dopt%3DAbstract Authors: Pearse G, Pietersma A, Cunliffe J, Foster JR, Turton J, Derbyshire N, Randall KJ In 2005, the International conference on harmonization (ICH) recommended that all new human pharmaceuticals be tested for unintended immunomodulatory potential via a tiered approach. Included in this approach is a semiquantitative description of changes in the separate compartments of lymphoid tissue (also called enhanced histopathology). Chlorambucil was administered to Hanover Wistar rats at regular time points, followed by a treatment-free (recovery) period. Groups of treated and control animals were sacrificed regularly during both the treatment and recovery periods. Selected tissues were removed, weighed fresh and fixed in formalin, processed, and stained with hematoxylin and eosin. Blood sam... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2869042 Sun, 04 Oct 2009 23:00:00 +0100 2869042 http://www.medworm.com/index.php?rid=2869044&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19801503%26dopt%3DAbstract In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity. PMID: 19801503 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2869044 Thu, 01 Oct 2009 23:00:00 +0100 2869044 http://www.medworm.com/index.php?rid=2869043&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19801504%26dopt%3DAbstract We describe here histopathological findings during dog studies with a fairly selective MMPi AZM551248, that are consistent with these human clinical changes. They were characterized by a dose- and time-dependent formative connective tissue alteration we have termed "fibrodysplasia." The most sensitive site was the subcuticular connective tissue, although musculoskeletal tissues were also extensively involved. In the subcutis, changes occurred initially around pre-existing blood vessels, but then more diffusely. There was proliferation of cells showing myofibroblast differentiation identified by elevated levels of alpha-smooth muscle actin, fibronectin, and transforming growth factor beta, and the deposition of collagen type III with a lesser quantity of collagen type I. On longer-term admi... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2869043 Thu, 01 Oct 2009 23:00:00 +0100 2869043 http://www.medworm.com/index.php?rid=2828679&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19773592%26dopt%3DAbstract Authors: Ochoa R, Rousseaux C PMID: 19773592 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2828679 Thu, 24 Sep 2009 23:12:02 +0100 2828679 http://www.medworm.com/index.php?rid=2828678&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19773593%26dopt%3DAbstract We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2828678 Thu, 24 Sep 2009 23:12:02 +0100 2828678 http://www.medworm.com/index.php?rid=2828677&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19773594%26dopt%3DAbstract Authors: Kalaiselvan P, Mathur KY, Pande VV, Madheswaran R, Bhelonde JJ, Shelar PD, Udupa V, Shingatgeri VM Intralobar nephroblastematosis (ILNB) is a precursor lesion to the development of nephroblastoma (NB) in rats. Unilateral ILNB was observed in the kidney of a nine-week-old female Wistar rat (Crl:WI) from a short-term toxicity study. Clinical pathology and urinalysis did not reveal altered renal function. This microscopic, unencapsulated lesion consisted of basophilic sheets of blastemal cells that did not include a prominent mesenchymal component. These cells expanded in the interstitium, which trapped and compressed few normal renal tubules. The blastemal cells moderately differentiated to form rosettes, primitive tubules, and a glomeruloid body. Multifocally, the lumen of prim... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2828677 Thu, 24 Sep 2009 23:12:02 +0100 2828677 http://www.medworm.com/index.php?rid=2828681&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19770348%26dopt%3DAbstract Authors: Ramot Y, Eliahu SB, Kagan L, Ezov N, Nyska A Olive oil is commonly employed as a solubilizing agent for lipophilic materials in preclinical studies in rodents. Here we report that following subcutaneous (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas formed, which were associated with an unusual location of the same changes in the peritoneum. Macroscopically, multifocal white spots were found over the liver and mesentery. Histologically, lipid granulomas were seen in the SC injection site, as well as on the capsular or serosal surface of the abdominal organs. No abnormal clinical signs were noted except for swelling at the injection site. The olive oil may have reached the peritoneal cavity from the SC tissue passively via the lymphatic vessels... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2828681 Sun, 20 Sep 2009 23:00:00 +0100 2828681 http://www.medworm.com/index.php?rid=2828680&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19770349%26dopt%3DAbstract Authors: Nyska A, Cunningham M, Snell M, Malarkey D, Sutton D, Dunnick J Electron microscopy and light microscopy have been used to evaluate the cardiotoxicity of bis(2-chloroethoxy)methane (CEM) in F344/N rats and B6C3F1 mice. Rats received vehicle control or CEM at 50 mg/kg/day, and mice, vehicle control or CEM at doses up to 100 mg/kg/day, by oral gavage for up to sixteen days. Cardiotoxicity in rats at 50 mg/kg consisted of myocardial degeneration, including myocardial inflammation, myofiber vacuolation, and/or myofiber necrosis. There was no light microscopic evidence for cardiotoxicity in mice even at doses twice that of rats, but cardiotoxic damage was seen after electron microscopic evaluations including mitochondrial disintegration and vacuolation. Mice with mitochondrial dama... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2828680 Sun, 20 Sep 2009 23:00:00 +0100 2828680 http://www.medworm.com/index.php?rid=2738699&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19706931%26dopt%3DAbstract This report documents another spontaneous heart lesion in clinically healthy monkeys for consideration during interpretation of toxicology studies. PMID: 19706931 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2738699 Mon, 24 Aug 2009 23:00:00 +0100 2738699 http://www.medworm.com/index.php?rid=2738698&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19706932%26dopt%3DAbstract Authors: Schafer K, Francke-Carroll S, Hutto D, Neef N, Silverman L, Vahle J, Whitney K PMID: 19706932 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2738698 Mon, 24 Aug 2009 23:00:00 +0100 2738698 http://www.medworm.com/index.php?rid=2733901&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700656%26dopt%3DAbstract In this study, we used an ultrasensitive cTnI immunoassay to quantify hourly concentrations of cTnI in live rats handled under standard laboratory conditions using 15 microL of serum per determination. The baseline reference range (mean 4.94 pg/mL, range 1-15 pg/mL, 99% confidence interval [CI]) of cTnI concentration in rats was consistent with previously reported reference ranges for cTnI in humans (1-12 pg/mL) and with preliminary studies in dogs (1-4 pg/mL) and monkeys (4-5 pg/mL) using the same cTnI assay method. In addition, cTnI concentrations in individual rat serum samples show minimal biological variability over a twenty-four-hour interval when compared to a meaningful reference change value of 193% to 206%. Furthermore, measurements of cTnI concentration were consistent within th... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733901 Thu, 20 Aug 2009 23:00:00 +0100 2733901 http://www.medworm.com/index.php?rid=2733900&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700657%26dopt%3DAbstract Authors: Oslund KL, Hyde DM, Putney LF, Alfaro MF, Walby WF, Tyler NK, Schelegle ES The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP8-37) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP8-37 had signifi... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733900 Thu, 20 Aug 2009 23:00:00 +0100 2733900 http://www.medworm.com/index.php?rid=2733897&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700658%26dopt%3DAbstract Authors: Boobis AR, Cohen SM, Doerrer NG, Galloway SM, Haley PJ, Hard GC, Hess FG, Macdonald JS, Thibault S, Wolf DC, Wright J The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be de... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733897 Thu, 20 Aug 2009 23:00:00 +0100 2733897 http://www.medworm.com/index.php?rid=2733896&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700659%26dopt%3DAbstract Authors: Long GG, Reynolds VL, Dochterman LW, Ryan TE The carcinogenic potential of naveglitazar, a gamma-dominant peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist, was evaluated in a two-year study in F344 rats (0, 0.3, 1.0, or 3.0 mg/kg, males; 0, 0.1, 0.3, or 1.0 mg/kg, females). Increased mortality in male rats of the high-dose group was related to cardiac-associated lesions, neoplasms, and undetermined causes. Degeneration and hypertrophy of the myocardium occurred with dose-responsive increased incidence and severity. Neoplasms with increased incidence included sarcomas in male rats and urinary bladder neoplasms in female rats. Most sarcomas in male rats occurred in the adipose tissue of the subcutis and were diagnosed as fibrosarcomas, with fewer liposa... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733896 Thu, 20 Aug 2009 23:00:00 +0100 2733896 http://www.medworm.com/index.php?rid=2733894&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700660%26dopt%3DAbstract Authors: Sano T, Ozaki K, Kodama Y, Matsuura T, Narama I 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 might also lead to SCC in human oral mucosa. Thus, the present study was conducted to examine the effects of the antifungal agent itraconazole (ITCZ) on proliferative and inflammatory changes of the forestomach in alloxan-induced diabetic WBN/Kob rats. Diabetes was induced by alloxan at fifteen weeks of age. Rats were allocated to three groups at forty-five weeks of age and were given ITCZ by gavage 0 (vehicle contro... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733894 Thu, 20 Aug 2009 23:00:00 +0100 2733894 http://www.medworm.com/index.php?rid=2733893&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19700661%26dopt%3DAbstract Authors: Sharma AK, Searfoss GH, Reams RY, Jordan WH, Snyder PW, Chiang AY, Jolly RA, Ryan TP Mesial temporal lobe epilepsy (MTLE) is a severe neurological condition of unknown pathogenesis for which several animal models have been developed. To obtain a better understanding of the underlying molecular mechanisms and identify potential biomarkers of lesion progression, we used a rat kainic acid (KA) treatment model of MTLE coupled with global gene expression analysis to examine temporal (four hours, days 3, 14, or 28) gene regulation relative to hippocampal histopathological changes. The authors recommend reviewing the companion histopathology paper (Sharma et al. 2008) to get a better understanding of the work presented here. Analysis of filtered gene expression data using Ingenuity P... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2733893 Thu, 20 Aug 2009 23:00:00 +0100 2733893 http://www.medworm.com/index.php?rid=2717033&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19690150%26dopt%3DAbstract Authors: Atalic B, Fatovic-Ferencic S 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 regulations of animal experiments. Although one might assume that the regulation had its origin in the United Nations conventions, the truth is that its origins are a hundred years old. The authors present a case of the nineteenth-century vivisection controversy brought about by the publication of the Handbook for the Physiological Laboratory in 1873, in which John Burdon-Sanderson, Emanuel Edward Klein, Michael Foster, and Thomas Lauder Brunto... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2717033 Mon, 17 Aug 2009 23:00:00 +0100 2717033 http://www.medworm.com/index.php?rid=2717032&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19690151%26dopt%3DAbstract In conclusion, although no clinical signs of renal disease were evident, the use of meglumine antimoniate in the pharmacological treatment approach of CanL-affected dogs should be carefully considered. PMID: 19690151 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2717032 Mon, 17 Aug 2009 23:00:00 +0100 2717032 http://www.medworm.com/index.php?rid=2717031&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19690152%26dopt%3DAbstract Authors: Kawai M, Saegusa Y, Jin M, Dewa Y, Nishimura J, Harada T, Shibutani M, Mitsumori K To clarify the mechanism of piperonyl butoxide (PBO)-induced hepatocarcinogenesis in mice, male mice were subjected to a two-thirds partial hepatectomy, N-diethylnitrosamine (DEN) initiation, and a diet containing 0.6% PBO for eight weeks. The incidence of gamma-glutamyl transpeptidase (GGT)-positive foci and PCNA-positive cells was significantly increased in the DEN + PBO group compared with the DEN-alone group. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis showed up-regulation of genes related to metabolism, such as cytochrome P450 1A1 and 2B10, and metabolic stress, such as Por, Nqo1, Nrf2, abcc3, and abcc4. Early responsive genes downstream of mitogen-activated ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2717031 Mon, 17 Aug 2009 23:00:00 +0100 2717031 http://www.medworm.com/index.php?rid=2702591&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19679887%26dopt%3DAbstract This study was performed to examine the carcinogenic effects of benzo[a]pyrene (B[a]P) and manufactured gas plant (MGP) residues on the hamster cheek pouch (HCP). Syrian hamsters were treated topically with a suspension of 2%, 10%, or 20% B[a]P or 50% or 100% MGP-7 (a mixture of residues from 7 MGP sites) in mineral oil for eight (short-term study) and sixteen, twenty, twenty-eight, and thirty-two weeks (long-term study). The short-term study showed that B[a]P induced p53 protein accumulation, indicative of genotoxic damage, as well as increased cell proliferation, hyperplasia, and inflammation, which is usually associated with promotional activity. In contrast, the MGP-7 presented only marginal p53 accumulation and induction of BrdU incorporation. In the long-term experiments, animals tre... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2702591 Wed, 12 Aug 2009 23:00:00 +0100 2702591 http://www.medworm.com/index.php?rid=2658232&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19638439%26dopt%3DAbstract Authors: Alden CL PMID: 19638439 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2658232 Fri, 31 Jul 2009 18:34:02 +0100 2658232 http://www.medworm.com/index.php?rid=2658231&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19638440%26dopt%3DAbstract Authors: 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-Calderon R, Patel SA, Kumarathasan P, Vincent R, Henríquez-Roldán C, Torres-Jardón R, Maronpot RR 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 ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2658231 Fri, 31 Jul 2009 18:34:02 +0100 2658231 http://www.medworm.com/index.php?rid=2658230&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19638441%26dopt%3DAbstract Authors: Keenan C, Elmore S, Francke-Carroll S, Kerlin R, Peddada S, Pletcher J, Rinke M, Schmidt SP, Taylor I, Wolf DC PMID: 19638441 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2658230 Fri, 31 Jul 2009 18:34:02 +0100 2658230 http://www.medworm.com/index.php?rid=2658229&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19638442%26dopt%3DAbstract Authors: Vahle J, Bradley A, Harada T, Herbert R, Kaufmann W, Kellner R, Mann P, Pyrah I, Rittinghausen S, Tanaka T PMID: 19638442 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2658229 Fri, 31 Jul 2009 18:34:02 +0100 2658229 http://www.medworm.com/index.php?rid=2584642&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19581239%26dopt%3DAbstract Authors: Mowat V, Turton J, Stewart J, Lui KC, Pilling AM Capillaria hepatica is a nematode parasite of wild rodents and other mammals. Adult worms inhabit the liver. Recently, during the necropsy examination of a group of 160 rabbits from a commercial supplier, firm pale or cystic areas (1-5 mm) were noted on the liver in thirteen animals. On further investigation, these animals were found to be infected with C. hepatica. The histopathological features of the infection in the rabbit are described for the first time and diagnostic features recorded. Lesions were identified predominantly in portal tracts consisting of dilated bile ducts with luminal debris, peribiliary inflammatory cell infiltrates, and fibrosis. Large granulomas (macrogranulomas) were evident in portal areas and involv... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2584642 Tue, 30 Jun 2009 23:00:00 +0100 2584642 http://www.medworm.com/index.php?rid=2538944&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19359541%26dopt%3DAbstract Authors: Savolainen SM, Foley JF, Elmore SA In humans, congenital heart diseases are common. Since the rapid progression of transgenic technologies, the mouse has become the major animal model of defective cardiovascular development. Moreover, genetically modified mice frequently die in utero, commonly due to abnormal cardiovascular development. A variety of publications address specific developmental stages or structures of the mouse heart, but a single reference reviewing and describing the anatomy and histology of cardiac developmental events, stage by stage, has not been available. The aim of this color atlas, which demonstrates embryonic/fetal heart development, is to provide a tool for pathologists and biomedical scientists to use for detailed histological evaluation of hematoxyl... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538944 Sat, 27 Jun 2009 21:38:06 +0100 2538944 http://www.medworm.com/index.php?rid=2538943&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380838%26dopt%3DAbstract Authors: Foster JR PMID: 19380838 [PubMed - indexed for MEDLINE] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538943 Sat, 27 Jun 2009 21:38:06 +0100 2538943 http://www.medworm.com/index.php?rid=2538941&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380839%26dopt%3DAbstract Authors: Boudonck KJ, Mitchell MW, Német L, Keresztes L, Nyska A, Shinar D, Rosenstock M Drug-induced nephrotoxicity is a major concern, since many pharmacological compounds are filtered through the kidneys for excretion into urine. To discover biochemical biomarkers useful for early identification of nephrotoxicity, metabolomic experiments were performed on Sprague-Dawley Crl:CD (SD) rats treated with the nephrotoxins gentamicin, cisplatin, or tobramycin. Using a combination of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), a global, nontargeted metabolomics analysis was performed on urine and kidney samples collected after one, five, and twenty-eight dosing days. Increases in polyamines and amino acids were observed in urine fro... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538941 Sat, 27 Jun 2009 21:38:06 +0100 2538941 http://www.medworm.com/index.php?rid=2538939&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380840%26dopt%3DAbstract Authors: Tannehill-Gregg SH, Dominick MA, Reisinger AJ, Moehlenkamp JD, Waites CR, Stock DA, Sanderson TP, Cohen SM, Arnold LL, Schilling BE In carcinogenicity studies with PPAR gamma and alpha/gamma agonists, urinary bladder tumors have been reported in Harlan Sprague-Dawley (HSD) and Charles River Sprague-Dawley (SD) but not Wistar (WI) rats, with urolithiasis purported to be the inciting event. In two 3-month studies, the authors investigated strain-related differences in urine composition by sampling urine multiple times daily. Urine pH, electrolytes, creatinine, protein, citrate and oxalate levels, and serum citrate were assessed; urine sediment was analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. HSD rats had significantly higher urine calcium th... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538939 Sat, 27 Jun 2009 21:38:06 +0100 2538939 http://www.medworm.com/index.php?rid=2538937&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380841%26dopt%3DAbstract Authors: Kambara T, McKevitt TP, Francis I, Woodfine JA, McCawley SJ, Jones SA, Pilling AM, Lewis DJ, Williams TC Large eosinophilic cytoplasmic inclusions (ECIs) are occasionally seen in untreated rat Clara cells. Following inhalation exposure to a corticosteroid, the number of ECIs was increased. This is the first histopathological description of rat ECIs and attempted characterization by immunohistochemistry, in situ hybridization, and electron microscopy. ECIs were strongly positive for surfactant protein D (SP-D) and weakly positive for Clara cell specific protein (CCSP). Clara cell cytoplasm was positive for CCSP mRNA regardless of ECIs, but not within ECIs. Corticosteroid treatment and ECI presence did not affect the immunohistochemistry and in situ hybridization staining intens... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538937 Sat, 27 Jun 2009 21:38:06 +0100 2538937 http://www.medworm.com/index.php?rid=2538934&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380842%26dopt%3DAbstract Authors: Herculiani PP, Pires-Neto RC, Bueno HM, Zorzetto JC, Silva LC, Santos AB, Garcia RC, Yonamine M, Detregiachi CR, Saldiva PH, Mauad T Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronch... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538934 Sat, 27 Jun 2009 21:38:06 +0100 2538934 http://www.medworm.com/index.php?rid=2538932&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380843%26dopt%3DAbstract This report provides additional histopathological evidence of peripheral nerve neoplasms in mice. PMID: 19380843 [PubMed - indexed for MEDLINE] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538932 Sat, 27 Jun 2009 21:38:06 +0100 2538932 http://www.medworm.com/index.php?rid=2538931&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380844%26dopt%3DAbstract Authors: Radi ZA, Metz A A well-circumscribed, expansile, and nonencapsulated cardiac rhabdomyoma composed of tightly arranged, large, variably sized, ovoid to irregular, swollen myocytes with deeply eosinophilic cytoplasm and varying degrees of cytoplasmic vacuolation was detected in an eight- to nine-month-old female beagle dog in a routine toxicology study. By histochemistry, the neoplasm was periodic acid-Schiff positive. By immunohistochemistry (IHC), neoplastic cells were positive for desmin and myoglobin and negative for vimentin and smooth muscle actin. Spontaneous lesions in the heart of young beagle dogs are rare in drug safety studies. On the basis of histopathology, histochemistry, and IHC findings, a diagnosis of cardiac rhabdomyoma was made. Cardiac rhabdomyoma is one of ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538931 Sat, 27 Jun 2009 21:38:06 +0100 2538931 http://www.medworm.com/index.php?rid=2538930&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380845%26dopt%3DAbstract Authors: Howroyd P, Allison N, Foley JF, Hardisty J Rare tumors were observed in chronic studies in F-344 rats that were purely or largely free in the mediastinal cavity, yet had the histological architecture of alveolar bronchiolar tumors. They had originally been diagnosed as either pulmonary alveolar bronchiolar tumors, mediastinal mesotheliomas, or thymomas. The authors described these tumors, estimated the fraction of thoracic tumors that they represented, and carried out a preliminary immunohistochemical investigation of whether they were of pulmonary or mesothelial origin. Sections of 715 thoracic tumors originally diagnosed as alveolar bronchiolar tumors, mesotheliomas, or thymomas from control or treated F-344 rats in NTP two-year studies were reviewed. Thirty (4%) were found ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538930 Sat, 27 Jun 2009 21:38:06 +0100 2538930 http://www.medworm.com/index.php?rid=2538929&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380846%26dopt%3DAbstract Authors: Cockerell G, Meuten D, Ochoa R PMID: 19380846 [PubMed - indexed for MEDLINE] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538929 Sat, 27 Jun 2009 21:38:06 +0100 2538929 http://www.medworm.com/index.php?rid=2538928&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380847%26dopt%3DAbstract Authors: Green JD PMID: 19380847 [PubMed - indexed for MEDLINE] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538928 Sat, 27 Jun 2009 21:38:06 +0100 2538928 http://www.medworm.com/index.php?rid=2538927&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19387086%26dopt%3DAbstract Authors: Wang A, Wolf DC, Sen B, Knapp GW, Holladay SD, Huckle WR, Caceci T, Robertson JL Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeare... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538927 Sat, 27 Jun 2009 21:38:06 +0100 2538927 http://www.medworm.com/index.php?rid=2538926&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19387087%26dopt%3DAbstract Authors: Bruner RH, Novilla MN, Picut CA, Kirkpatrick JB, O'Neill TP, Scully KL, Lawrence WB, Goodman DG, Saladino BH, Peters DG, Parker GA Hibernomas are rare neoplasms originating in brown adipose tissue of humans and other animal species, including laboratory animals. Background incidence values for these tumors in all common strains of laboratory rats are generally accepted as being <0.1%. Between April 2000 and April 2007, however, sixty-two hibernomas (an overall prevalence of 3.52%) were observed in a total of 1760 Sprague-Dawley rats assigned to three carcinogenesis bioassays at two separate research laboratories. All rats were obtained from Charles River's breeding facilities in either Portage, Michigan, or Raleigh, North Carolina. Tumors (twenty-nine benign and thirty-thre... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538926 Sat, 27 Jun 2009 21:38:06 +0100 2538926 http://www.medworm.com/index.php?rid=2538925&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19387088%26dopt%3DAbstract Authors: Grim KC, Wolfe M, Braunbeck T, Iguchi T, Ohta Y, Tooi O, Touart L, Wolf DC, Tietge J In support of an Organization for Economic Cooperation and Development (OECD) Amphibian Metamorphosis Assay (AMA) Test Guideline for the detection of substances that interact with the hypothalamic-pituitary-thyroid axis, a document was developed that provides a standardized approach for evaluating the histology/histopathology of thyroid glands in metamorphosing Xenopus laevis tadpoles. Here, a consolidated description of histology evaluation practices, core diagnostic criteria and severity grading schemes for the AMA, an atlas of the normal architecture of amphibian thyroid glands over the course of metamorphosis, and the core diagnostic criteria with examples of severity grades is provided. C... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538925 Sat, 27 Jun 2009 21:38:06 +0100 2538925 http://www.medworm.com/index.php?rid=2538924&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19387089%26dopt%3DAbstract The objective of this study was to understand the role of alcohol in altering estrogen levels in females by examining the effect of ethanol (EtOH) on the estrous cycle and then investigate the potential relationship between estradiol (E2) and hepatobiliary OPN expression in a female rat ASH model. Ovariectomized (OVX) and E2-implanted OVX rats in the ASH group were evaluated for OPN mRNA and protein expression. Low doses of E2 resulted in significant down-regulation of OPN protein and mRNA as compared to the OVX group. However, with increasing doses of E2, there was up-regulation of both OPN mRNA and protein. Osteopontin was localized primarily to the biliary epithelium. Liver injury assessed by serum ALT and histopathology revealed a pattern similar to OPN expression. In all groups, hepat... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538924 Sat, 27 Jun 2009 21:38:06 +0100 2538924 http://www.medworm.com/index.php?rid=2538923&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19389872%26dopt%3DAbstract Authors: Mori Y, Izawa T, Takenaka S, Kuwamura M, Yamate J Macrophages are crucial in hepatic fibrogenesis. In acute hepatic necrosis induced in rats by a single injection of 300 mg/kg body weight (BW) of thioacetamide (TAA), macrophage properties were investigated using single or double immunohistochemistry. Macrophages reacting with anti-CD68, anti-CD163, or major histocompatibility complex (anti-MHC) class II antibody appeared in injured centrilobular areas on days 1-5 after injection. Increased expression of CD68 and CD163 reflect phagocytosis and production of pro-inflammatory factors, respectively. There were also macrophages double-positive to CD68/CD163, CD68/MHC class II, or CD163/MHC class II; of these, macrophages double-positive to CD68/MHC class II were most frequent, indi... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538923 Sat, 27 Jun 2009 21:38:06 +0100 2538923 http://www.medworm.com/index.php?rid=2538922&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19389873%26dopt%3DAbstract Authors: Dewa Y, Nishimura J, Jin M, Kawai M, Saegusa Y, Harada T, Shibutani M, Mitsumori K The present study was performed to characterize molecular expression levels of preneoplastic and neoplastic lesions induced by beta-naphthoflavone (BNF), an aryl hydrocarbon receptor (AhR) agonist in rat hepatocarcinogenesis. Male F344 rats were initiated with an intraperitoneal injection of 200 mg/kg N-diethylnitrosamine, and two weeks later, they were fed a diet containing 0% or 1% BNF for twenty-eight weeks. All animals were subjected to a two-thirds partial hepatectomy at week 3 and sacrificed at week 30. Histopathologically, BNF increased the incidence and multiplicity of altered foci (1.7-fold and 3.3-fold) and hepatocellular adenomas (HCAs) (4.0-fold and 4.7-fold). Immunohistochemically, ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538922 Sat, 27 Jun 2009 21:38:06 +0100 2538922 http://www.medworm.com/index.php?rid=2538921&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19389874%26dopt%3DAbstract Authors: Wagner JG, Harkema JR, Jiang Q, Illek B, Ames BN, Peden DB Compared to healthy subjects, individuals with allergic airway disease (e.g., asthma, allergic rhinitis) have enhanced inflammatory responses to inhaled ozone. We created a rodent model of ozone-enhanced allergic nasal responses in Brown Norway rats to test the therapeutic effects of the dietary supplement gamma-tocopherol (gammaT). Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0% or 0.5% OVA (in saline) on Days 1 and 2, and then exposed to 0 or 1 ppm ozone (eight hours/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT (p.o., in corn oil) on days 2 through 5, beginning twelve hours after the last OVA challenge. On Day 6, nasal tissues were collected for histological evaluation and mor... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538921 Sat, 27 Jun 2009 21:38:06 +0100 2538921 http://www.medworm.com/index.php?rid=2538920&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19395589%26dopt%3DAbstract Authors: Okada M, Sano F, Ikeda I, Sugimoto J, Takagi S, Sakai H, Yanai T Morphological changes and mRNA expression levels in type-1 predominant soleus and type-2 predominant tensor fasciae latae muscles of rats treated with fenofibrate were investigated. After fenofibrate by oral gavage at 300 mg/kg/day for 28 days, degeneration/necrosis and regeneration of muscle fibers, cellular infiltration, and fibrosis were seen in soleus muscle. Additionally, expression of PDK4, CPT1-M, CPT2, and FACO mRNAs was increased. In contrast, no morphological changes or mRNA induction were apparent in tensor fasciae latae muscle. These data suggest that sensitivity to fenofibrate-induced muscle toxicity differs among muscles, with only type-1 fibers being susceptible. The up-regulation of PDK4, CPTs and... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538920 Sat, 27 Jun 2009 21:38:06 +0100 2538920 http://www.medworm.com/index.php?rid=2538919&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19395590%26dopt%3DAbstract Authors: Morrison JP, Ton TV, Collins JB, Switzer RC, Little PB, Morgan DL, Sills RC Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible lesions in the central nervous system. In the present study, the time course for the development of the neurotoxicological lesions was defined and the gene expression changes occurring in the posterior colliculus upon exposure to COS were characterized. Fischer 344 rats were exposed to 0 or 500 ppm COS for one, two, three, four, five, eight, or ten days, six hours per day. On days 1 and 2, no morphological changes were detected; on day 3, 10/10 (100%) rats had necrosis in the posterior colliculi; and on day 4 and later, necrosis was observed in numerous areas of the brain. Important gene expression changes occurring in the post... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538919 Sat, 27 Jun 2009 21:38:06 +0100 2538919 http://www.medworm.com/index.php?rid=2538918&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19395591%26dopt%3DAbstract In this study, we directly evaluate the role of IL-10 in liver injury by a pretreatment with anti-IL-10 neutralizing antibody (IL-10Ab). Rats were given goat IgG or IL-10Ab before being treated with CHX (CHX group or IL-10Ab/CHX group). In the CHX group, the CHX treatment markedly induced hepatic mRNA and serum protein levels of IL-10. The up-regulation of IL-10 was significantly suppressed in the IL-10Ab/CHX group. Blocking IL-10 in the IL-10Ab/CHX group led to greater increases in hepatic mRNA and serum levels of proinflammatory cytokines, such as TNF-alpha and IL-6. The IL-10Ab/CHX group developed more severe hepatocellular apoptosis, neutrophil transmigration, and necrotic change of hepatocytes compared with the CHX group. The caspase activities and mRNA levels of Cc120, LOX-1, and E-s... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538918 Sat, 27 Jun 2009 21:38:06 +0100 2538918 http://www.medworm.com/index.php?rid=2538916&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19458388%26dopt%3DAbstract This report demonstrates that the cellular composition, morphology, and immunohistochemical staining profile of normal metrial glands are similar to reported granular cell neoplasms in rats and mice. The possibility of a non-neoplastic lesion involving the metrial gland should be considered when proliferative lesions involving granulated cells are observed in the uterus of mice and rats from nonclinical toxicity studies. Positive immunohistochemical staining for perforin and S100 would assist in the classification of such lesions as a reactive metrial gland or decidual reaction. PMID: 19458388 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538916 Sat, 27 Jun 2009 21:38:06 +0100 2538916 http://www.medworm.com/index.php?rid=2538915&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19458389%26dopt%3DAbstract Authors: De Feo F, Jacobson S, Nyska A, Pagani P, Traverso CE The purpose of this study was to evaluate the histological biocompatibility of a stainless steel miniature glaucoma drainage device. Twenty-four months before death due to heart failure, this seventy-three-year-old female patient underwent filtration surgery for primary open-angle glaucoma uncontrolled in the right eye. The device was implanted at the limbus under a scleral flap. For histopathological evaluation, two corneoscleral specimens were embedded in methacrylate blocks sectioned to a thickness of 50 microns, polished and stained with periodic acid schiff. Some sections included a longitudinal cross-section of the implant. At the interface between the spur and the flange of the device and the cornea, there was a small... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538915 Sat, 27 Jun 2009 21:38:06 +0100 2538915 http://www.medworm.com/index.php?rid=2538914&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19458390%26dopt%3DAbstract Authors: Ohta T, Masutomi N, Tsutsui N, Sakairi T, Mitchell M, Milburn MV, Ryals JA, Beebe KD, Guo L Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying pharmacology and hepatotoxicology, Fischer 344 male rats were dosed with 300 mg/kg/day of fenofibrate for 14 days and the urine and plasma were analyzed on days 2 and 14. A combination of liquid and gas chromatography mass spectrometry returned the profiles of 486 plasma and 932 urinary metabolites. Aside from known pharmacological effects, such as accelerated fatty acid b... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538914 Sat, 27 Jun 2009 21:38:06 +0100 2538914 http://www.medworm.com/index.php?rid=2538913&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19458391%26dopt%3DAbstract Authors: Ettlin RA, Bolon B, Pyrah I, Konishi Y, Black HE Recent international summits of the International Federation of Societies of Toxicologic Pathologists have debated the desirability and potential means by which the proficiency of an individual toxicologic pathologist might be recognized and communicated throughout the world. The present article describes the advantages and disadvantages of implementing such a global recognition system by any means and provides a proposal whereby recognition might be accorded via rigorous credential review of a practitioner's education and experience. PMID: 19458391 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538913 Sat, 27 Jun 2009 21:38:06 +0100 2538913 http://www.medworm.com/index.php?rid=2538905&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19549929%26dopt%3DAbstract Authors: Engle SK, Jordan WH, Pritt ML, Chiang AY, Davis MA, Zimmermann JL, Rudmann DG, Heinz-Taheny KM, Irizarry AR, Yamamoto Y, Mendel D, Schultze AE, Cornwell PD, Watson DE Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, as... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538905 Mon, 22 Jun 2009 23:00:00 +0100 2538905 http://www.medworm.com/index.php?rid=2538907&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535489%26dopt%3DAbstract Authors: Zhang J, Goering PL, Espandiari P, Shaw M, Bonventre JV, Vaidya VS, Brown RP, Keenan J, Kilty CG, Sadrieh N, Hanig JP The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, ma... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538907 Tue, 16 Jun 2009 23:00:00 +0100 2538907 http://www.medworm.com/index.php?rid=2538906&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535490%26dopt%3DAbstract Authors: Golomb E, Nyska A, Schwalb H 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. Ischemic tolerance is modulated by ubiquitous signal transduction pathways, transcription factors and cellular enzymes, converging on the mitochondria as the main end effector. Therefore, drugs and toxins affecting these pathways may impair cardiac ischemic tolerance without affecting myocardial integrity or function in oxygenated conditions. Such effect would not be detected by current toxicological studies but would considerably influence t... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538906 Tue, 16 Jun 2009 23:00:00 +0100 2538906 http://www.medworm.com/index.php?rid=2538908&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19516052%26dopt%3DAbstract This article presents some possible ways of incorporating the HCD when analyzing data from a rodent cancer bioassay. Specifically, exploratory (informal) and formal statistical procedures for analyzing such data are reviewed. The boxplot is presented as an exploratory tool that describes the current data in the context of the distribution of the HCD. It will also identify potential outliers that would not be otherwise be flagged using standard methods such as the mean, standard deviation, and range. The various options for the statistical analysis of HCD presented here do not necessarily represent standard practice. PMID: 19516052 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538908 Tue, 09 Jun 2009 23:00:00 +0100 2538908 http://www.medworm.com/index.php?rid=2538910&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19487255%26dopt%3DAbstract Authors: Yee KK, Pribitkin EA, Cowart BJ, Vainius AA, Klock CT, Rosen D, Hahn CG, Rawson NE Few studies have examined the induction of squamous metaplasia in human olfactory nasal tissue caused by tobacco use and the implications it may have for olfaction, particularly when there are pre-existing insults, such as chronic rhinosinusitis (CRS). Quantitative histopathological analyses were performed on Alcian blue- and H&E-stained sections of nasal biopsies taken from the upper aspect of the middle turbinate of CRS patients. Chronic rhinosinusitis patients who were current smokers had a predominance of squamous metaplasia in the olfactory sensory epithelium, whereas CRS patients who were nonsmokers and were not exposed to secondhand cigarette smoke had a prevalence of goblet cell hype... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538910 Sun, 31 May 2009 23:00:00 +0100 2538910 http://www.medworm.com/index.php?rid=2538909&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19487256%26dopt%3DAbstract Authors: Nagatani M, Ando R, Yamakawa S, Saito T, Tamura K Among spontaneous neoplasms of the rat central nervous system, the discrimination between astrocytoma and malignant reticulosis (MR) is sometimes difficult because of their similar cell morphology and infiltration patterns. In the present study, we carried out histological and immunohistochemical analyses on a total of sixty-four cases in Sprague-Dawley and F344 rats. These cases were diagnosed as benign/malignant astrocytoma containing no neoplastic oligodendroglial elements or MR according to the diagnostic criteria of the World Health Organization International Classification of Rodent Tumors (Mohr et al. 1994). Astrocytomas were divided into three types and MR into two types based on the number of lesions, cellularity and i... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538909 Sun, 31 May 2009 23:00:00 +0100 2538909 http://www.medworm.com/index.php?rid=2538911&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19478280%26dopt%3DAbstract Authors: Ramot Y, Meiron M, Toren A, Steiner M, Nyska A The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolated from full-term human placentae, cultured on carriers, and expanded in a bioreactor called the PluriX. These cells can be expanded in vitro without phenotypic or karyotypic changes. We studied the safety and biodistribution properties of PLX-PAD cells following intramuscular administration in NOD/SCID mice. No significant clinical signs, hematological and biochemical parameters, or major pathological changes were fo... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538911 Wed, 27 May 2009 23:00:00 +0100 2538911 http://www.medworm.com/index.php?rid=2538912&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19474416%26dopt%3DAbstract We examined whether high incidence rates (18%-56%) of inflammation in the root of the aorta detected in a Balb/c mouse model for hind limb ischemia were related to the surgical procedure. Twenty mice underwent ligation of the femoral artery; incidences of aortic root inflammation were compared to those observed in controls. We used a multiple-section sampling method to increase the sensitivity of the diagnostic rates. Although a cumulative incidence of 12.5% was found, no difference was seen in the overall incidence rates between the control and the surgically treated groups. Evaluation of blood levels of inflammatory cytokines showed that ligation of the femoral artery produced higher levels of interleukin-6 in the surgically transected group of mice. The development of spontaneous arteri... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538912 Tue, 26 May 2009 23:00:00 +0100 2538912 http://www.medworm.com/index.php?rid=2538917&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454599%26dopt%3DAbstract Authors: Keenan C, Elmore S, Francke-Carroll S, Kemp R, Kerlin R, Peddada S, Pletcher J, Rinke M, Schmidt SP, Taylor I, Wolf DC PMID: 19454599 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2538917 Mon, 18 May 2009 23:00:00 +0100 2538917 http://www.medworm.com/index.php?rid=2315806&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332660%26dopt%3DAbstract Authors: Molyneux G, Rizzo S, Turton J, Phul P, Gibson F In vitro techniques for the culture of hemopoietic stem cells and committed hemopoietic progenitor cells in rat bone marrow have not been adequately described in the literature. In the present investigations, and using commercially available hemopoietic cytokines and growth factors, the conditions required to perform long-term bone marrow culture (LTBMC) using rat femoral bone marrow were studied, in conjunction with the colony-forming unit cell assay (CFU-C), to quantify the number of progenitor cells. CFU-C production by LTBMCs, set up using Iscove's modified Dulbecco's medium supplemented with fetal calf serum and horse serum, ceased after week 2 of culture. However, the duration of CFU-C production was significantly increased... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315806 Thu, 09 Apr 2009 16:10:17 +0100 2315806 http://www.medworm.com/index.php?rid=2315801&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332661%26dopt%3DAbstract Authors: Cardoso JF, Mendes FA, Amadeu TP, Romana-Souza B, Valença SS, Porto LC, Abreu JG, Monte-Alto-Costa A Cigarette smoke has been associated with poor healing in several studies, but the precise mechanisms involving this impairment are still not elucidated. The aim of this work was to investigate cigarette smoke exposure effects on initial phases of cutaneous healing in mice, focusing mainly on gene expression of two molecules involved in wound repair (Ccn2/Ctgf and Tgfb1) and to study if these effects are strain dependent. Mice were exposed to the smoke of nine cigarettes per day, three times per day, for ten days. In the eleventh day an excisional wound was made. The control group was sham-exposed. The cigarette smoke exposure protocol was performed until euthanasia, seven ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315801 Thu, 09 Apr 2009 16:10:17 +0100 2315801 http://www.medworm.com/index.php?rid=2315797&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332662%26dopt%3DAbstract Authors: Fujimoto K, Kumagai K, Ito K, Arakawa S, Ando Y, Oda S, Yamoto T, Manabe S Recently, it was reported that the intraperitoneal administration of 30 mg/kg/day troglitazone to heterozygous superoxide dismutase 2 gene knockout (Sod2+/-) mice for twenty-eight days caused liver injury, manifested by increased serum ALT activity and hepatic necrosis. Therefore, we evaluated the reproducibility of troglitazone-induced liver injury in Sod2+/- mice, as well as their validity as an animal model with higher sensitivity to mitochondrial toxicity by single-dose treatment with acetaminophen in Sod2+/- mice. Although we conducted a repeated dose toxicity study in Sod2+/- mice treated orally with 300 mg/kg/day troglitazone for twenty-eight days, no hepatocellular necrosis was observed in our s... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315797 Thu, 09 Apr 2009 16:10:17 +0100 2315797 http://www.medworm.com/index.php?rid=2315792&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332663%26dopt%3DAbstract In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated i... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315792 Thu, 09 Apr 2009 16:10:17 +0100 2315792 http://www.medworm.com/index.php?rid=2315787&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332664%26dopt%3DAbstract In conclusion, estrogen was shown to inhibit the development of pancreatic islet lesions toward inflammation and fibrosis but did not inhibit the occurrence of hemorrhagic lesions. PMID: 19332664 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315787 Thu, 09 Apr 2009 16:10:17 +0100 2315787 http://www.medworm.com/index.php?rid=2315782&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332665%26dopt%3DAbstract This report provides additional histopathological evidence of malignant hepatic nonepithelial tumors in mice. PMID: 19332665 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315782 Thu, 09 Apr 2009 16:10:17 +0100 2315782 http://www.medworm.com/index.php?rid=2315777&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19332666%26dopt%3DAbstract CONCLUSIONS: Taken together, these results indicate that in utero and postnatal ETS exposure is associated with altered parenchymal lung development. PMID: 19332666 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315777 Thu, 09 Apr 2009 16:10:17 +0100 2315777 http://www.medworm.com/index.php?rid=2315766&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19346503%26dopt%3DAbstract In this study, we examined the translocation pathway of intratracheally instilled C60 fullerene particles from the lung into the blood circulation in the mouse. Using light microscopy, aggregated particles of fullerene were observed in the capillary lumen in the lung and the pulmonary lymph nodes immediately after instillation. Electron microscopic analysis demonstrated an increased number of pinocytotic vesicles (caveolae) of various sizes in the type 1 alveolar epithelial cells (AEC) and endothelial cells; occasional caveolae containing some particulate substances were observed. In addition, particles of various sizes were observed throughout the structure of the air-blood barrier (ABB). These findings suggest that fullerene particles may pass the ABB by both diffusion and caveolae-media... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315766 Fri, 03 Apr 2009 04:00:00 +0100 2315766 http://www.medworm.com/index.php?rid=2315771&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19336671%26dopt%3DAbstract Authors: Shimo T, Ashizawa N, Moto M, Matsumoto K, Iwanaga T, Nagata O The present studies were performed to investigate the possible mechanism of marked species differences on nephropathy found in the long-term toxicity study of FYX-051, a xanthine oxidoreductase inhibitor. In the twenty-six-week dose toxicity study in the rat, in which FYX-051 was administered by oral gavage at 0.04, 0.2, and 1 mg/kg, xanthine-mediated nephropathy was seen only at 1 mg/kg, despite the presence of xanthine crystals in urine at 0.2 mg/kg and more; however, in the fifty-two-week dose toxicity study in the monkey, in which FYX-051 was administered by oral gavage at 30, 100, and 300 mg/kg, no toxicities were seen, even at 300 mg/kg. These outcomes showed there would be 1500-fold or more differences in the... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2315771 Tue, 31 Mar 2009 04:00:00 +0100 2315771 http://www.medworm.com/index.php?rid=2237815&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19258306%26dopt%3DAbstract Authors: Cullen JM, Brown DL, Kissling GE, Foley JF, Rizzo J, Marion PL, Parron VI, French JE The authors investigated the spectrum of tumors and Trp53 mutations in genetically engineered models using the FVB/N mouse that expressed the hepatitis B virus genome and/or carried a Trp53 null and wildtype allele and/or were exposed to aflatoxin B1. Liver tumor incidence was increased when all three risk factors were present. Without aflatoxin B1 exposure, neither Trp53 haploinsufficiency nor HBV expression affected liver tumor development. Liver tumor prevalence increased with aflatoxin B1 exposure (p < .001), as thirteen of fourteen mice with liver tumors were initiated with aflatoxin B1. Liver tumors were more frequent in males (12/190) than females (2/170). Seventy-three mice develope... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2237815 Mon, 02 Mar 2009 05:00:00 +0100 2237815 http://www.medworm.com/index.php?rid=2230136&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19252180%26dopt%3DAbstract Authors: Mioko Yoshizaki Akinaga L, Lichtenfels AJ, Carvalho-Oliveira R, Caldini EG, Dolhnikoff M, Ferraz Silva LF, Bueno HM, Pereira LA, Saldiva PH, Bueno Garcia ML To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles </= 0.3 microm) placed 20 m from a street with heavy traffic in downtown Sao Paulo, twenty-four hours per day for four months. Fine particle (PM2.5) concentration was determined gravimetrically; hearts were analyzed by morphometry. There was a reduction of the PM2.5 inside the filtered chamber (filtered = 8.61+/-0.79 microg/m(3), nonfiltered = 18.05+/-1.25 microg/m(3), p < .001). Coronary arteries showed no evidence o... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2230136 Fri, 27 Feb 2009 05:00:00 +0100 2230136 http://www.medworm.com/index.php?rid=2214380&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19234234%26dopt%3DAbstract Authors: Radi ZA Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandins (PGs), which play a significant role in health and disease in the gastrointestinal tract (GI) and in the renal, skeletal, and ocular systems. COX-1 is constitutively expressed and found in most normal tissues, whereas COX-2 can be expressed at low levels in normal tissues and is highly induced by pro-inflammatory mediators. Inhibitors of COX activity include: (1) conventional nonselective, nonsteroidal anti-inflammatory drugs (ns-NSAIDs) and (2) COX-2 selective nonsteroidal anti-inflammatory drugs (COX-2 s-NSAIDs). Inhibition of COX-1 often elicits GI toxicity in animals and humans. Therefore, COX-2 s-NSAIDs were developed to provide a selective COX-2 agent, while minimizing the atten... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2214380 Thu, 26 Feb 2009 10:21:35 +0100 2214380 http://www.medworm.com/index.php?rid=2214379&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19234235%26dopt%3DAbstract Authors: Vickers AE Impairment of liver mitochondrial beta-oxidation is an important mechanism of drug-induced liver injury. Four inhibitors of fatty acid oxidation were compared in short-term rat in vivo studies in which the rats were administered one or four doses. The hepatocellular vacuolation represented ultra-structural mitochondrial changes. Urine nuclear magnetic resonance (NMR) spectroscopy revealed that both FOX988 and SDZ51-641 induced a persistent dicarboxylic aciduria, suggesting an inhibition of mitochondrial beta-oxidation and incomplete fatty acid metabolism. Etomoxir caused minimal mitochondrial ultrastructural changes and induced only transient dicarboxylic aciduria. CPI975 served as a negative control, in that there were no significant perturbations to the mitochondr... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2214379 Thu, 26 Feb 2009 10:21:35 +0100 2214379 http://www.medworm.com/index.php?rid=2159108&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19188468%26dopt%3DAbstract Authors: Mackie JT, Atshaves BP, Payne HR, McIntosh AL, Schroeder F, Kier AB Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARalpha-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catala... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2159108 Mon, 02 Feb 2009 05:00:00 +0100 2159108 http://www.medworm.com/index.php?rid=2159107&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19188469%26dopt%3DAbstract Authors: Wells MY, Voute H, Lonchampt MO, Fisch C, Boulifard V, Picaut P The somatostatin analog octreotide was administered to male and female Sprague-Dawley rats by subcutaneous injection for thirteen weeks at 0 (saline control), 0 (placebo control [mannitol and lactic acid; pH 4.2]), 1.25 mg/kg/day and 2.5 mg/kg/day to explore its potential effect on cutaneous vascular morphology. The placebo caused an increase in the incidence of intimal hyperplasia compared to saline controls in female rats; octreotide increased the incidence and severity of intimal hyperplasia in males and females. Intimal hyperplasia consisted of increased numbers of cells located between the endothelial cell layer and the internal elastic lamina. Severity was based on the degree of compromise of the vascular lu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2159107 Mon, 02 Feb 2009 05:00:00 +0100 2159107 http://www.medworm.com/index.php?rid=2155233&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19182213%26dopt%3DAbstract Authors: Ivetic Tkalcevic V, Cuzic S, Parnham MJ, Pasalic I, Brajsa K The full-thickness wound in the genetically diabetic (db/db) mouse is a commonly used model of impaired wound healing. We investigated delayed healing of non-occluded, excisional, full-thickness, dermal wounds in db/db mice in comparison to their normal littermate controls and refined methods for monitoring skin wound re-epithelialization, contraction, granulation tissue formation, and inflammation. We have confirmed with a computer-assisted planimetry method the results of previous studies showing that healing of non-occluded full excision wounds in db/db mice does not occur by contraction as much as in healthy mice. In addition, we have developed separate histological methods for the assessment of re-epithelializat... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2155233 Mon, 02 Feb 2009 05:00:00 +0100 2155233 http://www.medworm.com/index.php?rid=2155235&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19181629%26dopt%3DAbstract Authors: Pearse G, Frith J, Randall KJ, Klinowska T Unexpected deaths occurred in studies involving a nude mouse model of mammary cancer that required subcutaneous implantation of 0.5 mg twenty-one-day release estrogen pellets for growth of the estrogen-dependent mammary tumor xenograft BT474c. Early deaths occurred in female nude mice and were associated with urinary retention, frequently with cystitis. Drug treatment had no effect on the incidence or severity of cystitis. Histological findings did not alter significantly over various time points following pellet implantation. Changes were not seen in males or in females receiving lower doses of estradiol even when the duration of administration was prolonged, suggesting that a threshold level was required for the onset of urinary ret... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2155235 Thu, 29 Jan 2009 05:00:00 +0100 2155235 http://www.medworm.com/index.php?rid=2155234&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19181630%26dopt%3DAbstract Authors: Meyerholz DK, Griffin MA, Castilow EM, Varga SM A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was evaluated in tissue sections of neutrophilic soft tissue lesions and bone marrow from respective animals. Eosinophils had granular red to orange-red cytoplasmic staining, depending on the method, whereas neutrophils had, when stained, a more homogenous cytoplasmic pattern. Nonspecific background staining of similar coloration was variably seen in vascular walls and erythrocytes. Astra Blue/Vital New Red, Congo Red, Lu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2155234 Thu, 29 Jan 2009 05:00:00 +0100 2155234 http://www.medworm.com/index.php?rid=2140134&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171926%26dopt%3DAbstract Authors: Watterson C, Lanevschi A, Horner J, Louden C Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140134 Mon, 26 Jan 2009 05:00:00 +0100 2140134 http://www.medworm.com/index.php?rid=2140133&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171927%26dopt%3DAbstract Authors: Ju C ABSTRACTIdiosyncratic drug reactions (IDR) account for approximately 6%-10% of all adverse drug reactions. The unpredictable and serious nature of these reactions makes them a significant economic burden and safety concern to the health care community and the pharmaceutical industry. Clinical and laboratory evidence suggests that adverse immune responses against drug-protein adducts play a role in the pathogenesis of IDR. However, it remains unclear why only a small percentage of patients are susceptible to developing these reactions. We hypothesized that most patients develop immunological tolerance against drug-protein adducts as a default mechanism, and that IDRs can only occur when this tolerance is deficient or abrogated in susceptible individuals. Using a murine mod... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140133 Mon, 26 Jan 2009 05:00:00 +0100 2140133 http://www.medworm.com/index.php?rid=2140132&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171928%26dopt%3DAbstract Authors: Flint OP, Noor MA, Hruz PW, Hylemon PB, Yarasheski K, Kotler DP, Parker RA, Bellamine A ABSTRACT Metabolic complications associated with HIV infection and treatment frequently present as a relative lack of peripheral adipose tissue associated with dyslipidemia and insulin resistance. In this review we explain the connection between abnormalities of intermediary metabolism, observed either in vitro or in vivo, and this group of metabolic effects. We review molecular mechanisms by which the HIV protease inhibitor (PI) class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage. We then propose that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse e... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140132 Mon, 26 Jan 2009 05:00:00 +0100 2140132 http://www.medworm.com/index.php?rid=2140131&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171929%26dopt%3DAbstract Authors: Ponce R, Miller D ABSTRACT Atacicept, a fully human recombinant fusion protein that blocks the activity of BLyS (B-Lymphocyte Stimulator) and APRIL (a proliferation-inducing ligand), is undergoing clinical evaluation in B-cell-mediated diseases, including autoimmune disorders. Nonclinical studies in mice and cynomolgus monkeys demonstrate dose-dependent, reversible decreases in circulating Ig concentrations and reductions in mature B cells in the peripheral blood and lymphoid tissues. However, the combination of atacicept with purine synthesis inhibitors (e.g., mycophenolate mofetil [MMF]) and anti-B-cell monoclonal therapy (e.g., rituximab) has not been evaluated. Atacicept does not augment hematological toxicities associated with MMF, including anemia or thrombocytopenia. Co... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140131 Mon, 26 Jan 2009 05:00:00 +0100 2140131 http://www.medworm.com/index.php?rid=2140130&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171930%26dopt%3DAbstract Authors: Calderon-Garciduenas L, Macias-Parra M, Hoffmann HJ, Valencia-Salazar G, Henriquez-Roldan C, Osnaya N, Camacho-Del-Monte O, Barragan-Mejia G, Villarreal-Calderon R, Romero L, Granada-Macias M, Torres-Jardon R, Medina-Cortina H, Maronpot RR Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with th... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140130 Mon, 26 Jan 2009 05:00:00 +0100 2140130 http://www.medworm.com/index.php?rid=2140129&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19171931%26dopt%3DAbstract Authors: McBurney RN, Hines WM, von Tungeln LS, Schnackenberg LK, Beger RD, Moland CL, Han T, Fuscoe JC, Chang CW, Chen JJ, Su Z, Fan XH, Tong W, Booth SA, Balasubramanian R, Courchesne PL, Campbell JM, Graber A, Guo Y, Juhasz PJ, Li TY, Lynch MD, Morel NM, Plasterer TN, Takach EJ, Zeng C, Beland FA ABSTRACT Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2140129 Mon, 26 Jan 2009 05:00:00 +0100 2140129 http://www.medworm.com/index.php?rid=2111735&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19147833%26dopt%3DAbstract In this study, the complex mixture behaved in a doseadditive manner. Our results indicate that compounds that act by disparate mechanisms of toxicity display cumulative, dose-additive effects when present in combination. PMID: 19147833 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2111735 Thu, 15 Jan 2009 05:00:00 +0100 2111735 http://www.medworm.com/index.php?rid=2058377&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19098117%26dopt%3DAbstract Authors: Handelsman Y ABSTRACTMetabolic syndrome is a relatively new definition, designed to help the health care practitioner to easily identify people at risk for the development of cardiovascular disease and diabetes. With the obesity epidemic, we are witnessing an epidemic of multiple-risk patients. Insulin resistance is the perceived pathophysiology of metabolic syndrome and defines its clinical presentation. Hypertension, dyslipedemia, polycystic ovarian syndrome, fatty liver disease, pre-diabetes, sleep and breathing disorder, certain cancers, and cognitive impairment are many of the presentations of the syndrome; patients with any of these conditions are at a high risk of developing cardiovascular disease and diabetes. The metabolic syndrome helps identify people at risk to all... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2058377 Fri, 19 Dec 2008 05:00:00 +0100 2058377 http://www.medworm.com/index.php?rid=2058376&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19098118%26dopt%3DAbstract Authors: Teicher BA ABSTRACTPredicting whether a potential new anticancer agent will have a positive therapeutic index in patients remains a challenge. This brief review provides examples of preclinical in vivo/ex vivo and in situ assays used to assess the therapeutic potential of experimental anticancer therapeutics. Excision assays involving removal of tumor, bone marrow, and other tissues from the host after treatment to determine the effects of therapy in ex vivo assays are important preclinical tools. The survival of malignant cells from tumors treated in vivo and then excised is often determined by colony formation (CFU) in culture. When mice bearing in vivo alkylating agent-resistant tumors were treated with anticancer drugs such as cyclophosphamide, the survival pattern of bone... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2058376 Fri, 19 Dec 2008 05:00:00 +0100 2058376 http://www.medworm.com/index.php?rid=2044628&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075043%26dopt%3DAbstract Authors: Wang N, Symons JD, Zhang H, Jia Z, Gonzalez FJ, Yang T Thiazolidinediones (TZDs) are peroxisome proliferators-activated receptor gamma (PPARgamma) activators that exhibit antihypertensive and vasculoprotective effects. Here we describe the use of Tie2Cre/flox and SM22Cre/flox mice, which respectively lacked PPARgamma in the endothelium and the smooth muscle, to study vascular function of PPARgamma. Rosiglitazone (RGZ) induced a similar blood pressure (BP)-lowering effect in deoxycorticosterone acetate (DOCA) salt-treated PPARgamma(f/f ) and SM22Cre/flox mice, whereas Tie2Cre/flox mice were completely resistant to this effect. The femoral arteries lacking endothelial PPARgamma exhibited increased reactivity to various vasoconstrictors without a significant alteration in acetylc... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2044628 Mon, 15 Dec 2008 05:00:00 +0100 2044628 http://www.medworm.com/index.php?rid=2044627&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075044%26dopt%3DAbstract Authors: Anderson RM, Shanmuganayagan D, Weindruch R It is widely accepted that caloric restriction (CR) without malnutrition delays the onset of aging and extends lifespan in diverse animal models including yeast, worms, flies, and laboratory rodents. The mechanism underlying this phenomenon is still unknown. We have hypothesized that a reprogramming of energy metabolism is a key event in the mechanism of CR (Anderson and Weindruch 2007). Data will be presented from studies of mice on CR, the results of which lend support to this hypothesis. Effects of long-term CR (but not short-term CR) on gene expression in white adipose tissue (WAT) are overt. In mice and monkeys, a chronic 30% reduction in energy intake yields a decrease in adiposity of approximately 70%. In mouse epididymal WAT,... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=2044627 Mon, 15 Dec 2008 05:00:00 +0100 2044627 http://www.medworm.com/index.php?rid=1978721&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19020336%26dopt%3DAbstract Authors: Keller JM, Zelditch ML, Huet YM, Leamy LJ The contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant and teratogen that has been shown to alter craniofacial development. Differences in sensitivity to TCDD are attributed primarily to differences in alleles at the Ahr locus coding for the aryl-hydrocarbon receptor (AHR) that binds TCDD and mediates its effects by altering gene expression. The authors used geometric morphometric methods to evaluate differences in the effects of small in utero exposures of TCDD on adult mandible size and shape in five different inbred mouse strains with the same Ahr alleles. Because of the known effects of this toxicant on bone and craniofacial structures, the authors hypothesized that TCDD would decrease mandible siz... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=1978721 Wed, 19 Nov 2008 05:00:00 +0100 1978721 http://www.medworm.com/index.php?rid=1937023&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981453%26dopt%3DAbstract Authors: Patyna S, Arrigoni C, Terron A, Kim TW, Heward JK, Vonderfecht SL, Denlinger R, Turnquist SE, Evering W Sunitinib malate (SUTENT) is a multitargeted receptor tyrosine kinase (RTK) inhibitor that is approved multinationally for the treatment of imatinibresistant/-intolerant gastrointestinal stromal tumor and advanced renal cell carcinoma. This paper characterizes the organ toxicity of sunitinib in Sprague-Dawley rats and cynomolgus monkeys, and the reversibility of any treatment-induced effects. Rats and monkeys received sunitinib (0-15 and 0-20 mg/kg/day, respectively) orally on a consecutive daily dosing schedule for thirteen weeks or on an intermittent daily dosing schedule for up to nine months. Clinical observations and laboratory parameters were recorded. Necropsy was con... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=1937023 Mon, 03 Nov 2008 05:00:00 +0100 1937023 http://www.medworm.com/index.php?rid=1932475&cid=s_28424_32_f&fid=28424&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18978307%26dopt%3DAbstract Authors: Kawai M, Jin M, Nishimura J, Dewa Y, Saegusa Y, Matsumoto S, Taniai E, Shibutani M, Mitsumori K Fenofibrate (FF) has previously been shown to induce hepatocellular neoplasia in a conventional mouse bioassay (NDA 1993), but there has been no report to examine the carcinogenic susceptibility of rasH2 mice to this chemical. In the present study, male rasH2 mice were subjected to a two-thirds partial hepatectomy (PH), followed by an N-diethylnitrosamine (DEN) initiation twenty-four hours after PH, and given a diet containing 0, 1200, or 2400 ppm FF for seven weeks. The incidences of preneoplastic foci were significantly increased in mice from the FF-treated groups. Immunohistochemistry revealed that significant increases in proliferating cell nuclear antigen (PCNA)-positive cells ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=1932475 Fri, 31 Oct 2008 04:00:00 +0100 1932475