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. Thu, 09 Feb 2012 00:42:22 +0100 http://www.medworm.com/index.php?rid=5630619&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%3D22267650%26dopt%3DAbstract Authors: Dunnick JK, Brix A, Cunny H, Vallant M, Shockley KR Abstract The toxicity of polybrominated diphenyl ethers (PBDEs), flame-retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 and continuing to weaning on postnatal day (PND) 21. Offspring from the dams underwent PBDE direct dosing by gavage at the same dose as their dams from PND 12 to PND 21, and then after weaning for another thirteen weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis (Affymetrix Rat Genome 230 2.0 Array). Treatment with PBDE induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate < 0.01), but onl... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5630619 Fri, 27 Jan 2012 01:54:02 +0100 5630619 http://www.medworm.com/index.php?rid=5630618&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%3D22267651%26dopt%3DAbstract Authors: Bolton S, Hassall D, Hildebrand D, Brück W, Huang JK, Pluchino S, McKevitt T, Parry J, McFarlane M, Fagg R, Roulois A PMID: 22267651 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5630618 Fri, 27 Jan 2012 01:54:02 +0100 5630618 http://www.medworm.com/index.php?rid=5611820&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%3D22252912%26dopt%3DAbstract Authors: Veeramachaneni DN Abstract Conventional light microscopic evaluation of a semen ejaculate does not fully utilize potential indicators of functional impairment in sperm organelles. The technique described here facilitates critical evaluation of morphological features of spermatozoal organelles at an ultrastructural level and helps identify vulnerable targets. Compared with a battery of sperm function assays employed in andrology clinics, this relatively less expensive technique efficiently uses semen as biopsy material and thus serves as a comprehensive means to assess the impact of toxicants on the male reproductive system. PMID: 22252912 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5611820 Tue, 17 Jan 2012 05:00:00 +0100 5611820 http://www.medworm.com/index.php?rid=5611819&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%3D22252913%26dopt%3DAbstract This article will emphasize the critical role played by exposure during the juvenile stage of development. This article will also highlight several key issues that distinguish DIT testing of pharmaceuticals. Representatives from the pharmaceutical, biotechnology, academic, and regulatory sectors (both FDA and EMA) were brought together during a two-day workshop in May 2010 to consider the current state of the science of DIT as it pertains to the testing of pharmaceuticals. It is important to emphasize at the onset that there are currently no regulatory guidelines for either drugs or nondrug chemicals specifically focused on assessment of DIT, although some general guidelines are included in both developmental and reproductive toxicity and general immunotoxicology guidance documents. PM... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5611819 Tue, 17 Jan 2012 05:00:00 +0100 5611819 http://www.medworm.com/index.php?rid=5611821&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%3D22246543%26dopt%3DAbstract Authors: Pinches MD, Betts CJ, Bickerton SJ, Beattie L, Burdett LD, Thomas HT, Derbyshire NA, Moores M Abstract A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. To date, all evaluation studies have been made using 18 to 24 hour collection periods. However, shorter, more welfare friendly, urine collection periods are also used in industry. In this article, we quantify urinary biomarker concentration in serial paired sequential short and long urine collections from male rats administered varying concentrations of cisplatin. We calculate the rate of biomarker excretion in normal animals for both collection periods and the bias and correlation in urinary biomarker concentration between collection periods in d... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5611821 Fri, 13 Jan 2012 05:00:00 +0100 5611821 http://www.medworm.com/index.php?rid=5586790&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%3D22228792%26dopt%3DAbstract Authors: Kawabata TT, Evans EW Abstract The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5586790 Fri, 06 Jan 2012 05:00:00 +0100 5586790 http://www.medworm.com/index.php?rid=5586824&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%3D22222884%26dopt%3DAbstract Authors: Danilenko DM, Wang H Abstract A number of therapeutic immunomodulatory biologics, including antibodies, fusion proteins, and recombinant proteins, have been causally linked with serious adverse effects in humans. In nearly all cases, these serious adverse effects have been directly associated with the immunomodulatory biologic's intended pharmacologic activity or exaggerated pharmacology. Examples of immunomodulatory biologics known to cause serious adverse effects in the clinic ranging from immunostimulation and cytokine release syndrome (e.g., TGN1412) to immunosuppression with increased risk of opportunistic infections (e.g., TNF-α antagonists, anti-integrins) are presented. Specific examples of the nonclinical testing strategy used for the clinical risk assessment of ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5586824 Thu, 05 Jan 2012 05:00:00 +0100 5586824 http://www.medworm.com/index.php?rid=5586813&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%3D22222885%26dopt%3DAbstract Authors: Gilmour MI Abstract Air pollution has long been associated with health risks such as increased susceptibility to respiratory infections and potentiation of asthmatic-type responses. Experimental evidence in rodents indicates that air pollutants including diesel exhaust particles (DEPs), gases, and metals cause lung injury, inflammation, reduce aspects of host defense, and may potentiate allergic airway responses. Here we present evidence that diesel exhaust particles delivered by inhalation or aspiration can exacerbate allergic lung disease depending on the material's chemical properties. Genomic analysis of mouse lungs following instillation or inhalation of DEPs shows an alteration spectrum of pathways associated with immune signaling, cell metabolism, and oxidative stre... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5586813 Thu, 05 Jan 2012 05:00:00 +0100 5586813 http://www.medworm.com/index.php?rid=5586792&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%3D22222886%26dopt%3DAbstract Authors: Snyder PW Abstract The immune system functions primarily as a defense mechanism to provide protective immunity against microbial pathogens and cancer. The resulting protective responses occur through the complex interaction of tissues, cells, proteins, and molecular pathways that act in concert with other systems (e.g., nervous and endocrine) to provide the host with immunologic responses that cause pathologic processes seen primarily as inflammatory reactions. The pathologic responses can be attributed to either normal responses to infectious organisms and cancer cells, misdirected responses as in the case of hypersensitivity or autoimmune diseases, or deficient responses attributable to deficiencies or defects in components of the immune system. Pathologists need to have... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5586792 Thu, 05 Jan 2012 05:00:00 +0100 5586792 http://www.medworm.com/index.php?rid=5586791&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%3D22222887%26dopt%3DAbstract Authors: Peterson RA Abstract Regulatory T-cells (T(REG)) are diverse populations of lymphocytes that regulate the adaptive immune response in higher vertebrates. T(REG) delete autoreactive T-cells, induce tolerance, and dampen inflammation. T(REG) cell deficiency in humans (i.e., IPEX [Immunodysregulation, Polyendocrinopathy and Enteropathy, X-linked syndrome]) and animal models (e.g., "Scurfy" mouse) is associated with multisystemic autoimmune disease. T(REG) in humans and laboratory animal species are similar in type and regulatory function. A molecular marker of and the cell lineage specification factor for T(REG) is FOXP3, a forkhead box transcription factor. CD4(+) T(REG) are either natural (nT(REG)), which are thymus-derived CD4(+)CD25(+)FOXP3(+) T-cells, or inducible (i.e.,... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5586791 Thu, 05 Jan 2012 05:00:00 +0100 5586791 http://www.medworm.com/index.php?rid=5571697&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%3D22215510%26dopt%3DAbstract Authors: Morgan DL, Jokinen MP, Price HC, Gwinn WM, Palmer SM, Flake GP Abstract 2,3-Pentanedione (PD) is a component of artificial butter flavorings. The use of PD is increasing since diacetyl, a major butter flavorant, was associated with bronchiolitis obliterans (BO) in workers and has been removed from many products. Because the toxicity of inhaled PD is unknown, these studies were conducted to characterize the toxicity of inhaled PD across a range of concentrations in rodents. Male and female Wistar-Han rats and B6C3F1 mice were exposed to 0, 50, 100, or 200 ppm PD 6 h/d, 5 d/wk for up to 2 wk. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5, and 10 exposures, and histopathology was evaluated after 12 exposures. MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM wer... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571697 Tue, 03 Jan 2012 05:00:00 +0100 5571697 http://www.medworm.com/index.php?rid=5571696&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%3D22215511%26dopt%3DAbstract Authors: Sanchez-Soria P, Broka D, Monks SL, Camenisch TD Abstract Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571696 Tue, 03 Jan 2012 05:00:00 +0100 5571696 http://www.medworm.com/index.php?rid=5571695&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%3D22215512%26dopt%3DAbstract Authors: Ward JM, Rehg JE, Morse HC Abstract The immune and hematopoietic systems play an important role in the normal homeostasis of blood and blood cells and for immune responses to endogenous and exogenous processes and insults. In order to interpret histopathologic changes in the immune and hematopoietic systems, it is important to understand the normal anatomy and histology of the thymus, spleen, lymph nodes, bone marrow, and other tissues. The thymus, spleen, and lymph nodes can be categorized by anatomical compartments, each of which contributes to specific immune functions. Lesions may be diagnosed by interpretive or descriptive (semiquantitative) methods. The interpretation of these tissues by lesion in anatomical compartments should allow for better understanding of these... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571695 Tue, 03 Jan 2012 05:00:00 +0100 5571695 http://www.medworm.com/index.php?rid=5571694&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%3D22215513%26dopt%3DAbstract Authors: Fagerland JA, Wall HG, Pandher K, Leroy BE, Gagne GD Abstract The first electron microscopic images of biological specimens were made in the 1940s, and the next 30 years comprised an era of descriptive ultrastructure during which transmission electron microscopy (TEM) was integral to an explosion in cellular and molecular biology. However, when questions could no longer be answered by ultrastructural information alone, the use of TEM in biological research declined. Innovative molecular techniques and newer imaging technologies such as confocal fluorescence microscopy filled the gap, providing faster answers with less rigorous training as a prerequisite to data collection. The use of TEM in toxicologic pathology has paralleled the rise and fall of its popularity in other d... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571694 Tue, 03 Jan 2012 05:00:00 +0100 5571694 http://www.medworm.com/index.php?rid=5571693&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%3D22215514%26dopt%3DAbstract Authors: Davis B Abstract Endometrial stromal polyps (ESP) are a common spontaneous reproductive tract lesion in the female rat. However, there is limited information concerning the etiology, biology, and significance of these polyps as an end point in toxicology and carcinogenicity studies. This paper reviews relevant literature to address these aspects of ESP with respect to potential relevance to human uterine tumors. Endometrial stromal polyps in rodents appear as age-related lesions. There are only a few chemicals tested for carcinogenicity in rat and mouse cancer bioassays associated with increased incidence of ESP with no common characteristics or mechanism of action. Uterine endometrial polyps that occur in women and the uterine stromal polyps that occur in rodents have dis... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571693 Tue, 03 Jan 2012 05:00:00 +0100 5571693 http://www.medworm.com/index.php?rid=5571692&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%3D22215515%26dopt%3DAbstract Authors: Ellis JM, Paul DS, Depetrillo MA, Singh BP, Malarkey DE, Coleman RA Abstract The risk of hepatocellular carcinoma increases with the persistence of non-alcoholic fatty liver disease. Triacylglycerol synthesis is initiated by glycerol-3-phosphate acyltransferase (GPAT). Of four isoforms, GPAT1 contributes 30-50% of total liver GPAT activity, and we hypothesized that it might influence liver susceptibility to tumorigenesis. C57Bl/6 mice deficient in GPAT1 were backcrossed 6 times to C3H mice. After exposure to the carcinogen diethylnitrosamine (DEN) and the tumor promoter phenobarbital, male Gpat1(-/-) mice, compared with controls (Gpat1(+/+)), had 93% fewer macroscopically visible nodules per liver at 21 weeks of age and 39% fewer at 34 weeks of age. Microscopically, contro... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5571692 Tue, 03 Jan 2012 05:00:00 +0100 5571692 http://www.medworm.com/index.php?rid=5521307&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%3D22155928%26dopt%3DAbstract Authors: Bradley A, Mukaratirwa S, Petersen-Jones M Abstract The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperpla... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5521307 Fri, 09 Dec 2011 05:00:00 +0100 5521307 http://www.medworm.com/index.php?rid=5484757&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%3D22116770%26dopt%3DAbstract Authors: Maronpot RR PMID: 22116770 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484757 Fri, 09 Dec 2011 02:30:03 +0100 5484757 http://www.medworm.com/index.php?rid=5484756&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%3D22116771%26dopt%3DAbstract Authors: Burkhardt JE, Pandher K, Solter PF, Troth SP, Boyce RW, Zabka TS, Ennulat D Abstract A set of best practices for the conduct of histopathology evaluation in nonclinical safety studies was endorsed by the Society of Toxicologic Pathology (STP) in 2004. These best practices indicate that the study pathologist should have knowledge of the treatment group and access to all available study-related data for the animal from which the tissue was obtained. A new set of best practices for the conduct of histopathology review for safety biomarker qualification for nonclinical studies has been endorsed by the STP and is summarized in this document. These best practices are generally similar to those for nonclinical safety studies, specifically that the pathologist be "unblinded" or ha... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484756 Fri, 09 Dec 2011 02:30:03 +0100 5484756 http://www.medworm.com/index.php?rid=5484755&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%3D22116772%26dopt%3DAbstract Authors: Levin S PMID: 22116772 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484755 Fri, 09 Dec 2011 02:30:03 +0100 5484755 http://www.medworm.com/index.php?rid=5484754&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%3D22116773%26dopt%3DAbstract Authors: Krinke GJ PMID: 22116773 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484754 Fri, 09 Dec 2011 02:30:03 +0100 5484754 http://www.medworm.com/index.php?rid=5484753&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%3D22131108%26dopt%3DAbstract In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver. PMID: 22131108 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484753 Wed, 30 Nov 2011 05:00:00 +0100 5484753 http://www.medworm.com/index.php?rid=5484760&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%3D22109712%26dopt%3DAbstract Authors: Dewitt JC, Peden-Adams MM, Keller JM, Germolec DR Abstract Perfluorinated compounds (PFCs) are environmentally widespread, persistent, and bioaccumulative chemicals with multiple toxicities reported in experimental models and wildlife, including immunomodulation. The two most commonly detected compounds, which also generally occur in the highest concentrations in environmentally exposed organisms, are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). PFOA and PFOS have been reported to alter inflammatory responses, production of cytokines, and adaptive and innate immune responses in rodent models, avian models, reptilian models, and mammalian and nonmammalian wildlife. Mounting evidence suggests that immune effects in laboratory animal models occur at ser... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484760 Tue, 22 Nov 2011 05:00:00 +0100 5484760 http://www.medworm.com/index.php?rid=5484759&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%3D22109713%26dopt%3DAbstract Authors: Dewitt JC, Peden-Adams MM, Keil DE, Dietert RR Abstract Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to adulthood, including chemical, biological, physical, or physiological factors, alters immune system development. DIT may elicit suppression, hyperactivation, or misregulation of immune responses and therefore may present clinically as decreased resistance to pathogens, allergic and autoimmune diseases, and inflammatory diseases. When evaluating DIT in an animal model, specific endpoints are assessed, which can reveal the potential for a risk factor to alter immune system development. However, linking DIT evaluation in an animal model with clinical realities observed in human populations requires that DIT testing regimens eva... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484759 Tue, 22 Nov 2011 05:00:00 +0100 5484759 http://www.medworm.com/index.php?rid=5484758&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%3D22109714%26dopt%3DAbstract Authors: Song WC Abstract The complement system and toll-like receptors (TLRs) are two components of innate immunity that are critical for first-line host defense. Many pathogen-associated molecular patterns activate both complement and TLRs, and recent studies in animal models have revealed a marked synergistic interaction between the two systems. In mice deficient in a membrane complement regulator, prototypical TLR ligands such as LPS, zymosan, and polyI:C caused increased systemic complement activation, which in turn led to a profound elevation of proinflammatory cytokine biosynthesis. This phenotype required interaction between complement and TLRs because complement activation alone by cobra venom factor without TLR engagement did not lead to appreciable cytokine production. T... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484758 Tue, 22 Nov 2011 05:00:00 +0100 5484758 http://www.medworm.com/index.php?rid=5484766&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%3D22105644%26dopt%3DAbstract In conclusion, the fatty accumulation observed in BALB/c mice may be caused, at least in part, by up-regulation of fatty acid uptake and biosynthesis. Cd36, Acaca, Acly and Fasn may be involved in these metabolic processes. PMID: 22105644 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484766 Mon, 21 Nov 2011 05:00:00 +0100 5484766 http://www.medworm.com/index.php?rid=5484765&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%3D22105645%26dopt%3DAbstract Authors: McDonald B, Kubes P Abstract The liver is a target of many inflammatory pathologies of both infectious and noninfectious etiology. As key effectors of the innate immune system, neutrophils are critical for defense against microbial infections but are often the source of profound collateral damage to host tissues during disease states. In this article based on the authors' presentation at the 2011 Society of Toxicologic Pathology Annual Symposium, they review the molecular mechanisms of neutrophil recruitment to the liver in response to sepsis/endotoxemia, as well as sterile inflammation, and discuss variations in the molecular choreography of neutrophil trafficking in response to these different insults. Furthermore, the authors discuss the functional contributions of neut... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484765 Mon, 21 Nov 2011 05:00:00 +0100 5484765 http://www.medworm.com/index.php?rid=5484764&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%3D22105646%26dopt%3DAbstract Authors: Luebke R Abstract Current immunotoxicity testing guidance for drugs, high production-volume chemicals, and pesticides specifies the use of animal models to assess potential biomarkers of immune system effects (e.g., lymphoid organ and bone marrow indices, histopathology) or actual measures of immune function (e.g., responses to challenge with antigens or pathogens). These assays are resource intensive and often require special training or experience to ensure reliable results. Alternative in vitro assays to detect immunosuppression and allergic hypersensitivity have the potential to reduce animal use and testing costs and increase immunotoxicity screening and prioritization efforts. Alternative models to detect immunosuppression tend to address broad modes of action becaus... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484764 Mon, 21 Nov 2011 05:00:00 +0100 5484764 http://www.medworm.com/index.php?rid=5484763&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%3D22105647%26dopt%3DAbstract Authors: Barron MG Abstract The Deepwater Horizon (DWH) oil spill was the largest environmental disaster and response effort in U.S. history, with nearly 800 million liters of crude oil spilled. Vast areas of the Gulf of Mexico were contaminated with oil, including deep-ocean communities and over 1,600 kilometers of shoreline. Multiple species of pelagic, tidal, and estuarine organisms; sea turtles; marine mammals; and birds were affected, and over 20 million hectares of the Gulf of Mexico were closed to fishing. Several large-scale field efforts were performed, including assessments of shoreline and wildlife oiling and of coastal waters and sediments. The assessment of injuries, damages, and restoration options for the DWH spill is ongoing. Although petroleum and the polycyclic ar... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484763 Mon, 21 Nov 2011 05:00:00 +0100 5484763 http://www.medworm.com/index.php?rid=5484762&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%3D22105648%26dopt%3DAbstract Authors: Bolon B Abstract Autoimmune disease (AIDx) results from failure to sustain tolerance to self molecules. Dozens of AIDx involving one or multiple organ systems afflict 3% or more of people worldwide (>75% women). Predisposing factors for AIDx include genetic background, hormonal status, pathogens, and xenobiotic exposures. The incidence of AIDx is higher in individuals living in developed nations, including recent immigrants. Patients may have several AIDx simultaneously. Certain AIDx can prevent other AIDx. A history of AIDx raises the risk for developing hematopoietic neoplasia. Some common mechanisms for losing self-tolerance include reduced deletion or enhanced activation of autoreactive CD4(+) T-helper (Th) lymphocytes, defective immunomodulation by CD4(+) regulator... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484762 Mon, 21 Nov 2011 05:00:00 +0100 5484762 http://www.medworm.com/index.php?rid=5484761&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%3D22105649%26dopt%3DAbstract Authors: Weaver JL Abstract The first effective immunosuppressive drug (ISD) was azathioprine, approved in 1968. Early experience with this drug suggested that patients might have an excess risk of tumors including lymphoma and skin tumors. Comparison among various registries has shown that the cumulative risk of tumors increases over time. The risk is additionally increased by the more intense immunosuppressive regimens needed for lung or heart-lung transplants. The link between immunosuppression and tumorigenesis was further reinforced by the high concordance of tumor types between transplant and HIV patients. The role of the immune system in tumor defense includes both direct tumor surveillance and immunity against oncogenic viruses. In transplant patients, at least two-thirds o... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5484761 Mon, 21 Nov 2011 05:00:00 +0100 5484761 http://www.medworm.com/index.php?rid=5430588&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%3D22089838%26dopt%3DAbstract Authors: Janssen WJ, Henson PM Abstract In simple terms, inflammation can be defined as a beneficial, nonspecific response of tissues to injury that generally leads to restoration of normal structure and function. In this concept, resolution of the inflammatory response, once it has achieved its protective and pro-immunogenic functions, becomes a critical determinant of what might be considered the paradox of inflammation. On one hand, inflammation is essential to resolve tissue injury and maintain homeostasis. On the other, inflammation is a key participant in the great majority of human diseases. Accordingly, to achieve complete resolution of inflammation, it is necessary to both turn off inflammatory mediator production and inflammatory cell accumulation and to remove inflammato... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430588 Wed, 16 Nov 2011 05:00:00 +0100 5430588 http://www.medworm.com/index.php?rid=5430587&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%3D22089839%26dopt%3DAbstract This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430587 Wed, 16 Nov 2011 05:00:00 +0100 5430587 http://www.medworm.com/index.php?rid=5430586&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%3D22089840%26dopt%3DAbstract Authors: Kerkvliet NI Abstract I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my research career that has spanned the past 40 years as well. An initial focus on the immunotoxicity of pentachlorophenol led my laboratory into the aryl hydrocarbon receptor (AHR) field and the study of its most potent ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). My research career has been devoted to trying to elucidate the immunological basis of TCDD's profound immunosuppressive activity that is mediated by activation of AHR. In re... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430586 Wed, 16 Nov 2011 05:00:00 +0100 5430586 http://www.medworm.com/index.php?rid=5430585&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%3D22089841%26dopt%3DAbstract Authors: Menke A, Wolterbeek A, Snel C, Bruijntjes J, de Groot D, van Oostrum L, Waalkens I, Kuper CF Abstract Characteristic susceptibility to environmental and pharmaceutical exposure may occur during periods in life of marked histophysiological changes of the immune system. Perinatal development is such a period; pregnancy followed by lactation is potentially another one. Here, we explored the influence of pregnancy and lactation on the model immunotoxic compound di-n-octyltin dichloride (DOTC) in rats using clinical and histopathological parameters. Female rats were exposed to 0, 3, 10, or 30 mg DOTC/kg feed during pregnancy and up to 20 (at weaning) or 56 days after delivery. Age-matched nonmated females were exposed during the same time periods. DOTC at the level of 10 and 30... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430585 Wed, 16 Nov 2011 05:00:00 +0100 5430585 http://www.medworm.com/index.php?rid=5430584&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%3D22089842%26dopt%3DAbstract Authors: Parker GA, Picut CA Abstract The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are impo... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430584 Wed, 16 Nov 2011 05:00:00 +0100 5430584 http://www.medworm.com/index.php?rid=5430583&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%3D22089843%26dopt%3DAbstract Authors: Elmore SA Abstract Enhanced histopathology (EH) of the immune system is a tool that the pathologist can use to assist in the detection of lymphoid organ lesions when evaluating a suspected immunomodulatory test article within a subchronic study or as a component of a more comprehensive, tiered approach to immunotoxicity testing. There are three primary points to consider when performing EH: (1) each lymphoid organ has separate compartments that support specific immune functions; (2) these compartments should be evaluated individually; and (3) semiquantitative descriptive rather than interpretive terminology should be used to characterize any changes. Enhanced histopathology is a screening tool that should be used in conjunction with study data including clinical signs, gro... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430583 Wed, 16 Nov 2011 05:00:00 +0100 5430583 http://www.medworm.com/index.php?rid=5430582&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%3D22089844%26dopt%3DAbstract Authors: Schuh JC, Pearse G Abstract Session 3 of the Toxicologic Pathology and the Immune System Symposium, presented as part of the 30th Annual Symposium of the Society of Toxicologic Pathology in 2011, focused on the biological advances in control of selected cellular and secretory components of acquired immunity. Acquired immunity goes beyond innate immunity to provide controlled recognition and memory for specific antigenic challenges. Predominately involving activation of T and B lymphocytes, the resulting cellular- and secretory-mediated activity provides immediate and long-term host defenses to antigenic challenge. This session highlighted the biological advances in function and dysfunction of acquired immunity through regulatory T cells, the pathophysiology of effector cel... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430582 Wed, 16 Nov 2011 05:00:00 +0100 5430582 http://www.medworm.com/index.php?rid=5430592&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%3D22083583%26dopt%3DAbstract Authors: Sharma MR, Dworakowski W, Shapiro BH Abstract Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2-which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450-were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430592 Mon, 14 Nov 2011 05:00:00 +0100 5430592 http://www.medworm.com/index.php?rid=5430591&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%3D22083584%26dopt%3DAbstract In this study, the incidence of peritoneal sarcomatosis arising secondary to surgically implanted telemetry devices (< 15% of implanted Sprague Dawley rats) is considered to represent a significant issue for both animal welfare and data validity in affected animals. Macroscopically, the telemetry-associated fibrosarcomas spread along the visceral and parietal peritoneum and mesentery surrounding abdominal organs. The histologic morphology of these sarcomas was typically an undifferentiated sarcoma, although well-differentiated fibrosarcomas and telangiectatic and pleomorphic variants were noted. Using special stains such as Masson's Trichrome demonstrated a collagenous extracellular matrix in 50% of these rats, which is consistent with a fibroblastic origin. Immunohistochemical studies ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430591 Mon, 14 Nov 2011 05:00:00 +0100 5430591 http://www.medworm.com/index.php?rid=5430590&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%3D22083585%26dopt%3DAbstract Authors: Ramot Y, Rosenstock M, Klinger E, Bursztyn D, Nyska A, Shinar DM Abstract Glatiramer acetate (GA), the active ingredient in Copaxone®, is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, witho... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430590 Mon, 14 Nov 2011 05:00:00 +0100 5430590 http://www.medworm.com/index.php?rid=5430589&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%3D22083586%26dopt%3DAbstract Authors: Haley PJ Abstract As the molecular pathobiology of immunologically based diseases, such as rheumatoid arthritis, has become clearer, pharmaceutical researchers have responded with highly efficacious and selective biological compounds. In contrast to older, nonspecific small-molecule therapeutics, the exquisite species sensitivity of monoclonal antibodies has introduced new challenges to preclinical safety studies. Repeated exposure of animals to biopharmaceutical compounds tends to be restricted in the species in which these compounds have pharmacological action, and it tends to stimulate antidrug immune responses with acceleration of clearance, thereby limiting the duration of repeat-dose studies and potentially resulting in hypersensitivity reactions. Thus, the safety te... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5430589 Mon, 14 Nov 2011 05:00:00 +0100 5430589 http://www.medworm.com/index.php?rid=5364719&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%3D22033502%26dopt%3DAbstract Authors: Clark SM, Narayanan PK, Fort MM Abstract Regulatory T cells (Tregs) are a rare subset of lymphocytes that inhibit the activation and effector functions of T cells and are important regulators of immune responses. Although Tregs are well characterized in humans and rodents, little is known about their immunophenotyping (IP) profile in cynomolgus macaques (Macaca fascicularis), which is an important species for pharmacological and toxicological evaluation of potential immune modulators because of their similar physiologic, genetic, and metabolic response patterns to humans. The authors have developed an immunophenotyping panel using a high-throughput 96-well microtiter plate-based assay to detect circulating Tregs (CD3(+)CD4(+)CD25(hi)FoxP3(+)) and have determined the normal... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364719 Thu, 27 Oct 2011 04:00:00 +0100 5364719 http://www.medworm.com/index.php?rid=5364723&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%3D22021165%26dopt%3DAbstract This study was designed to investigate the toxico-pathological effects of in ovo inoculation of ochratoxin A (OTA) in chicken embryos and subsequently in the hatching chicks. Nine hundred fertile white leghorn (WL) layer breeder eggs were divided into eight groups (A-H). Group A was maintained as untreated control, whereas group B was kept as sham control (10 µL of 0.1 M NaHCO(3 )solution). Before incubation, groups C, D, E, F, G, and H were injected with 0.01, 0.03, 0.05, 0.10, 0.50, and 1.00 µg OTA/egg, respectively. At 53 hrs of incubation, crown to rump length, optic cups, and eye lens diameters were significantly (p ≤ .05) lower, whereas neural tube closure defects were higher in the OTA-treated embryos. Teratogenic defects (studied at day 9 of incubation) and embryonic mortalitie... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364723 Fri, 21 Oct 2011 04:00:00 +0100 5364723 http://www.medworm.com/index.php?rid=5364722&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%3D22021166%26dopt%3DAbstract Authors: Berman-Booty LD, Sargeant AM, Rosol TJ, Rengel RC, Clinton SK, Chen CS, Kulp SK Abstract The transgenic adenocarcinoma of the mouse prostate (TRAMP) model is well established and offers several advantages for the study of chemopreventive agents, including its well-defined course of disease progression and high incidence of poorly differentiated carcinomas within a relatively short length of time. However, there is no consensus on the grading of prostatic lesions in these mice. In particular, agreement is lacking on the criteria for differentiating prostatic intraepithelial neoplasia (PIN) from well-differentiated adenocarcinoma, specifically as it relates to evidence of invasion. This differentiation is critical for evaluating the effects of putative chemopreventive agents... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364722 Fri, 21 Oct 2011 04:00:00 +0100 5364722 http://www.medworm.com/index.php?rid=5364721&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%3D22021167%26dopt%3DAbstract This study investigated the effect of bark extract of Bathysa cuspidata on hepatic oxidative damage and blood glucose kinetics in rats exposed to paraquat. Wistar rats were exposed to a single dose of paraquat (30 mg/kg, i.p.) and treated with an ethanolic extract of Bathysa cuspidata (200 and 400 mg/kg). Analyses were conducted of liver edema, blood glucose, serum transaminases, alkaline phosphatase, collagen, malondialdehyde, catalase, superoxide dismutase, and histomorphometry. In the animals intoxicated with paraquat and treated with 400 mg/kg of extract, edema, hypertrophy of the nucleus of hepatocytes, serum transaminases, alkaline phosphatase, and malondialdehyde levels decreased significantly (p < .05). Catalase and superoxide dismutase activity, the number of hepatocytes per un... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364721 Fri, 21 Oct 2011 04:00:00 +0100 5364721 http://www.medworm.com/index.php?rid=5364720&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%3D22021168%26dopt%3DAbstract Authors: Wood CE, Stavisky RC, Nowak J, Kaplan JR Abstract Here, we report the effects of estrogen and the selective estrogen receptor modulator (SERM) levormeloxifene on adrenocortical measures in ovariectomized female cynomolgus monkeys (Macaca fascicularis). Animals were randomized into one of five treatment groups, each containing 23 to 26 animals: (1) placebo, (2) 0.016 mg/kg 17β-estradiol (E(2)), (3) 0.5 mg/kg levormeloxifene (L(1)), (4) 1.0 mg/kg levormeloxifene (L(2)), and (5) 5.0 mg/kg levormeloxifene (L(3)). Treatments were administered orally each day for 18 mo. All doses of levormeloxifene resulted in adrenal weights at least 50% greater than placebo (p < .0001 for all). The target dose of levormeloxifene (L(2)) resulted in higher serum concentrations of cortisol (+... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364720 Fri, 21 Oct 2011 04:00:00 +0100 5364720 http://www.medworm.com/index.php?rid=5364725&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%3D22006284%26dopt%3DAbstract Authors: Bauchet AL, Masson R, Guffroy M, Slaoui M Abstract Kidney is a major target organ in preclinical studies. In recent years, intense research has been undertaken to characterize novel renal toxicity biomarkers. In this context, we studied nephron segment specific antibodies against aquaporin-1 (AQP-1), α-glutathione-S-transferase (alpha-GST), Tamm-Horsfall protein (TH), calbindin-D(28K) (CalD), and aquaporin-2 (AQP-2), using an immunoperoxidase method on formalin-fixed paraffin-embedded kidney tissues of dogs, rats, mice, and Cynomolgus monkeys. AQP-1 was specific for proximal tubules and thin descending limbs of Henle's loops and AQP-2 for connecting and collecting ducts in dogs, rats, mice, and Cynomolgus monkeys. Alpha-GST stained the straight part of proximal tubules in... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364725 Mon, 17 Oct 2011 04:00:00 +0100 5364725 http://www.medworm.com/index.php?rid=5364724&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%3D22006285%26dopt%3DAbstract Authors: Rousseau I, Galleano M, Puntarulo S Abstract The hypothesis of this study was that alterations in Fe distribution triggered by lipopolysaccharide (LPS) administration were affected in vivo by Fe overload. Lipopolysaccharide treatment by itself significantly decreased Fe content in serum and increased the blood NO-hemoglobin (NO-Hb) EPR signal and nitrotyrosine protein content in liver, as compared to values in control animals. Fe overload (produced by Fe-dextran ip administration) caused an increase, as compared to values in control animals, in Fe content in serum, and a significant enhancement in ferritin (Ft) content, Fe content in Ft, the labile Fe pool (LIP), and the protein carbonyl content in the liver. The simultaneous administration of LPS and Fe-dextran lead to a ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5364724 Mon, 17 Oct 2011 04:00:00 +0100 5364724 http://www.medworm.com/index.php?rid=5287977&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%3D21859882%26dopt%3DAbstract Authors: Schultze AE, Reddy VR, Donnelly KB, Berridge BR Abstract The global practice of drug development is expanding into many different continents and countries. India, in particular, is rapidly emerging as an economic force in this arena by offering ever-expanding opportunities for pharmaceutical market expansion as well as productive drug development partnerships. The key to the country's current socioeconomic success appears to be education, particularly the development of higher and professional education. Also, recent modifications to India's patent laws offer greater protections and incentives for international investment. Increasing numbers of competent contract research organizations create attractive opportunities for large Western pharmaceutical companies with a desire... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287977 Thu, 06 Oct 2011 15:45:02 +0100 5287977 http://www.medworm.com/index.php?rid=5287976&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%3D21859885%26dopt%3DAbstract Authors: Houle CD Abstract The identification of neurotoxicity is a critical issue in drug development, and toxicologic pathologists play an important role in this effort. Neuropathology is a specialized area of toxicologic pathology in which a substantial number of nonroutine techniques and methods have been developed, and there are undoubtedly many instances in which these specialized procedures have helped characterize a neuropathologic lesion. Routine histopathologic methods employed in general toxicologic pathology studies are needed to identify the complete range of possible neuropathologic changes; once identified, many of these changes can be better defined by specialized techniques, such as immunohistochemistry, to confirm cell types involved. Sometimes, when neurotoxicity... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287976 Thu, 06 Oct 2011 15:45:02 +0100 5287976 http://www.medworm.com/index.php?rid=5287974&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%3D21971933%26dopt%3DAbstract Authors: Treumann S, Schneider S, Gröters S, Moore NP, Boor PJ Abstract Dissecting aortic aneurysms, generally involving the thoracic aorta, have been shown to be caused by specific aliphatic amines in developing rats. Whether such lesions might occur spontaneously in control rats is not known. Therefore, in this study, 1,016 four-day-old, untreated rats culled from ongoing scheduled breeding studies were subjected to gross and histopathological examination in order to create a background control data base on the incidence of spontaneous aortic dissecting aneurysms. Two animals (0.2%) were found to have small dissecting aortic aneurysms, and an additional 2 (0.2%) had only hemorrhagic lesions. All of these lesions were limited to the region of the ductus arteriosus. An additional ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287974 Thu, 06 Oct 2011 15:45:02 +0100 5287974 http://www.medworm.com/index.php?rid=5287973&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%3D21971934%26dopt%3DAbstract Authors: Dunstan RW, Wharton KA, Quigley C, Lowe A Abstract A morphology-based assay such as immunohistochemistry (IHC) should be a highly effective means to define the expression of a target molecule of interest, especially if the target is a protein. However, over the past decade, IHC as a platform for biomarkers has been challenged by more quantitative molecular assays with reference standards but that lack morphologic context. For IHC to be considered a "top-tier" biomarker assay, it must provide truly quantitative data on par with non-morphologic assays, which means it needs to be run with reference standards. However, creating such standards for IHC will require optimizing all aspects of tissue collection, fixation, section thickness, morphologic criteria for assessment, stai... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287973 Thu, 06 Oct 2011 15:45:02 +0100 5287973 http://www.medworm.com/index.php?rid=5287972&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%3D21971935%26dopt%3DAbstract Authors: Irizarry Rovira AR, Foley GL, Clemo FA PMID: 21971935 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287972 Thu, 06 Oct 2011 15:45:02 +0100 5287972 http://www.medworm.com/index.php?rid=5287971&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%3D21971936%26dopt%3DAbstract Counterpoint to "Analysis of Unbiased Histopathology Data from Rodent Toxicity Studies (or, Are These Groups Different Enough to Ascribe to Treatment?)". Toxicol Pathol. 2011;39(6):1017-9 Authors: Wolf JC PMID: 21971936 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287971 Thu, 06 Oct 2011 15:45:02 +0100 5287971 http://www.medworm.com/index.php?rid=5287970&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%3D21971937%26dopt%3DAbstract Authors: Harvey PW PMID: 21971937 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5287970 Thu, 06 Oct 2011 15:45:02 +0100 5287970 http://www.medworm.com/index.php?rid=5251653&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%3D21937740%26dopt%3DAbstract Authors: Kakiuchi-Kiyota S, Arnold LL, Yokohira M, Koza-Taylor P, Suzuki S, Varney M, Pennington KL, Cohen SM Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists are used in the treatment of type 2 diabetes mellitus and hyperlipidemias. In carcinogenicity studies, some of these agonists induced hemangiomas/hemangiosarcomas in mice, but not in rats. We hypothesized that increased endothelial cell (EC) proliferation may be involved in the mechanism of PPAR agonist-induced vascular tumors in mice. We previously showed that the sarcomagenic PPARγ agonist troglitazone (TG) increased EC proliferation in brown and white adipose tissue and liver in mice at sarcomagenic doses (400 and 800 mg/kg) after four weeks of treatment. In vitro, TG... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251653 Wed, 21 Sep 2011 04:00:00 +0100 5251653 http://www.medworm.com/index.php?rid=5251652&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%3D21937741%26dopt%3DAbstract Authors: Herman EH, Knapton A, Rosen E, Thompson K, Rosenzweig B, Estis J, Agee S, Lu QA, Todd JA, Lipshultz S, Hasinoff B, Zhang J Abstract Cardiotoxicity was an unanticipated side effect elicited by the clinical use of imatinib (Imb). This toxicity has been examined in only a limited number of experimental studies. The present study sought, by a variety of approaches, to identify important characteristics of Imb-induced cardiac alterations. Male spontaneously hypertensive rats (SHRs) received oral doses of 10, 30, or 50 mg/kg Imb or water daily for 10 d. Cardiac lesions, detected at all doses, were characterized by cytoplasmic vacuolization and myofibrillar loss. In a second experiment, cardiac lesions were found in Sprague Dawley (SD) and SHR rats given 50 or 100 mg/kg Imb for 1... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251652 Wed, 21 Sep 2011 04:00:00 +0100 5251652 http://www.medworm.com/index.php?rid=5251651&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%3D21937742%26dopt%3DAbstract In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels. PMID: 21937742 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251651 Wed, 21 Sep 2011 04:00:00 +0100 5251651 http://www.medworm.com/index.php?rid=5251657&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%3D21934138%26dopt%3DAbstract Authors: Takahashi N, Yoshida T, Ohnuma A, Horiuchi H, Ishitsuka K, Kashimoto Y, Kuwahara M, Nakashima N, Harada T Abstract Dimethylarsinic acid (DMA(V)), the major excreted metabolite of inorganic arsenic, is carcinogenic to the rat urinary bladder. Oxidative stress has been proposed as one possible mechanism of DMA(V)-induced carcinogenesis. The authors determined whether the antioxidant N-acetylcysteine (NAC) modifies DMA(V)-induced urinary bladder injury in rats. The treatment solutions-DMA(V) at 10 mg/kg, NAC at 90 or 1.6 mg/kg (high or low dose, respectively), and their combination-were intravesically instilled into female F344 rats over two hours under pentobarbital anesthesia. The treatment was conducted twice with an interval of three days. All animals were euthanized one ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251657 Tue, 20 Sep 2011 04:00:00 +0100 5251657 http://www.medworm.com/index.php?rid=5251656&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%3D21934139%26dopt%3DAbstract Authors: Suzuki S, Pitchakarn P, Takeshita K, Asamoto M, Takahashi S, Sato S, Shirai T Abstract In a previous study, to identify genes of importance for hepatocellular carcinogenesis, and especially for processes involved in malignant transformation, the authors investigated differences in gene expression between adenomas and carcinomas by DNA microarray. In the present study, the authors investigated AW434047, one of the sequences that was upregulated in carcinomas. The investigation led to the identification of a novel gene, which the authors named hepatocyte malignant transforming factor (HMTF), of unknown function whose expression was increased in hepatocellular carcinomas. Northern blot and in situ hybridization also demonstrated high levels of HMTF in rat hepatocellular carci... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251656 Tue, 20 Sep 2011 04:00:00 +0100 5251656 http://www.medworm.com/index.php?rid=5251655&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%3D21934140%26dopt%3DAbstract The objective of the present work was to evaluate in vivo osteal development in GJA1-deficient fetal mice through determination of the histological and molecular alterations induced by partial or total deletion of the GJA1 gene. Heterozygous C57BL/6 mice (HT) harboring a null mutation of the GJA1 gene were mated, and pregnant females were submitted to euthanasia and Caesarean section from 12.5 to 19.5 days post coitum (dpc). HT (GJA1(+/-)) and homozygous (GJA1(-/- )) knockout (KO) mutants and wild-type (WT) fetuses were identified by polymerase chain reaction (PCR), and development curves were constructed on the basis of fetus weight and crown-rump length. Histopathological, histochemical, and real-time PCR analyses were performed in order to assess the expression of markers associated wit... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251655 Tue, 20 Sep 2011 04:00:00 +0100 5251655 http://www.medworm.com/index.php?rid=5251654&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%3D21934141%26dopt%3DAbstract Authors: Gao X, Anderson DR, Brown AW, Lin H, Amnuaysirikul J, Chua AL, Holmes WW, Ray P Abstract Macrolide antibiotics have been shown to protect airway epithelial cells and macrophages from sulfur mustard (SM)-induced cytotoxicity. In the current study, the efficacy of roxithromycin in ameliorating SM-induced respiratory injury was further evaluated in a rat model. Anesthetized rats (N = 8/group) were intratracheally exposed to SM by vapor inhalation. For the drug treatment groups, rats were orally given 10, 20, or 40 mg/kg roxithromycin one hr prior to exposure and every twenty-four hr thereafter. After one, three, or seven days of treatment, sections of the lung were examined and scored for histopathological parameters. Treatment with roxithromycin ameliorated many of the sympt... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5251654 Tue, 20 Sep 2011 04:00:00 +0100 5251654 http://www.medworm.com/index.php?rid=5207247&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%3D21885873%26dopt%3DAbstract Authors: McKevitt TP, Giffen P, Woodfine JA, McCawley SJ, Papworth SA, McGill P, Osborne J, Beard P, Williams TC, Klapwijk J, Lewis DJ Abstract The purpose of this study was to compare the toxicity of three marketed corticosteroid receptor agonists (mometasone furoate, budesonide, or flunisolide) to the stomach of female CD-1 mice following oral administration via the diet for up to 52 weeks, with a 16-week recovery period (budesonide and flunisolide). A range of tissues was examined by light microscopy, accompanied by clinical pathology measurements to assess anticipated corticosteroid effects as a surrogate marker of systemic drug exposure. Microscopic changes seen in the stomach with each corticosteroid included pyloric hyalinization. This previously unreported finding was inves... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5207247 Thu, 01 Sep 2011 04:00:00 +0100 5207247 http://www.medworm.com/index.php?rid=5207246&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%3D21885874%26dopt%3DAbstract Authors: de David C, Rodrigues G, Bona S, Meurer L, González-Gallego J, Tuñón MJ, Marroni NP Abstract In hepatic toxicity induced in rats by two injections of thioacetamide (TAA, 350 mg/kg with an interval of 8 hr), the action of quercetin was investigated. After 96 hr, TAA administration resulted in hepatic necrosis, significant increases in serum transaminase activity, and increases in hepatic lipoperoxidation. Thioacetamide-induced hepatotoxicity also showed changes in antioxidant enzymes in the liver of rats, with alterations in p-ERK 1/2 (phosphorylated extracellular-signal related kinase 1/2) as well as an imbalance between proapototic protein Bax and anti-apoptotic protein Bcl-2 expression. With administration of the flavonoid quercetin (50 mg/Kg i.p.) for four consecutiv... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5207246 Thu, 01 Sep 2011 04:00:00 +0100 5207246 http://www.medworm.com/index.php?rid=5182661&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%3D21878552%26dopt%3DAbstract Authors: Carll AP, Haykal-Coates N, Winsett DW, Hazari MS, Nyska A, Richards JH, Willis MS, Costa DL, Farraj AK Abstract Spontaneously hypertensive heart failure rats (SHHFs) take longer to develop compensated heart failure (HF) and congestive decompensation than common surgical models of HF. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loading in hypertensive rats induces cardiac fibrosis, hypertrophy, and-in a minority-congestive HF. By combining ISO with dietary salt loading in young SHHFs, the authors sought a nonsurgical model that is more time- and resource-efficient than any of these factors alone. The authors hypothesized that salt loading would enhance ISO-accelerated cardiomyopathy, promoting fibrosis, hypertrophy, and bioc... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5182661 Mon, 29 Aug 2011 23:00:00 +0100 5182661 http://www.medworm.com/index.php?rid=5182660&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%3D21878553%26dopt%3DAbstract Authors: Kouchi M, Toyosawa K, Matsumoto I, Michimae Y, Tochitani T, Koujitani T, Okimoto K, Funabashi H, Seki T Abstract Hyaline glomerulopathy with tubulo-fibrillary deposits was observed in two young female ddY mice. One of the mice showed gross systemic edema and bilateral enlargement and pale color of the kidneys, whereas no significant gross findings were noted in the other mouse. Microscopically, a large number of the glomeruli in both mice were enlarged because of diffuse and global deposition of amorphous eosinophilic materials. The deposits were negatively stained with Congo red and positively stained with IgG, IgM, IgA, C3, and periodic acid-Schiff. Electron microscopic examination revealed microtubular and fibrillary deposits with diameters of 80-100 and 9-16 nm, respec... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5182660 Mon, 29 Aug 2011 23:00:00 +0100 5182660 http://www.medworm.com/index.php?rid=5169329&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%3D21859882%26dopt%3DAbstract Authors: Schultze AE, Reddy VR, Donnelly KB, Berridge BR Abstract The global practice of drug development is expanding into many different continents and countries. India, in particular, is rapidly emerging as an economic force in this arena by offering ever-expanding opportunities for pharmaceutical market expansion as well as productive drug development partnerships. The key to the country's current socioeconomic success appears to be education, particularly the development of higher and professional education. Also, recent modifications to India's patent laws offer greater protections and incentives for international investment. Increasing numbers of competent contract research organizations create attractive opportunities for large Western pharmaceutical companies with a desire... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169329 Sun, 21 Aug 2011 23:00:00 +0100 5169329 http://www.medworm.com/index.php?rid=5169328&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%3D21859883%26dopt%3DAbstract Authors: Morgan DL, Nyska A, Harbo SJ, Grumbein SL, Dill JA, Roycroft JH, Kissling GE, Cesta MF Abstract Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169328 Sun, 21 Aug 2011 23:00:00 +0100 5169328 http://www.medworm.com/index.php?rid=5169327&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%3D21859884%26dopt%3DAbstract Authors: Anderton MJ, Mellor HR, Bell A, Sadler C, Pass M, Powell S, Steele SJ, Roberts RR, Heier A Abstract Aberrant signaling by transforming growth factor-β (TGF-β) and its type I (ALK5) receptor has been implicated in a number of human diseases and this pathway is considered a potential target for therapeutic intervention. Transforming growth factor-β signaling via ALK5 plays a critical role during heart development, but the role of ALK5 in the adult heart is poorly understood. In the current study, the preclinical toxicology of ALK5 inhibitors from two different chemistry scaffolds was explored. Ten-week-old female Han Wistar rats received test compounds by the oral route for three to seven days. Both compounds induced histopathologic heart valve lesions characterized by he... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169327 Sun, 21 Aug 2011 23:00:00 +0100 5169327 http://www.medworm.com/index.php?rid=5169326&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%3D21859885%26dopt%3DAbstract Authors: Houle CD Abstract The identification of neurotoxicity is a critical issue in drug development, and toxicologic pathologists play an important role in this effort. Neuropathology is a specialized area of toxicologic pathology in which a substantial number of nonroutine techniques and methods have been developed, and there are undoubtedly many instances in which these specialized procedures have helped characterize a neuropathologic lesion. Routine histopathologic methods employed in general toxicologic pathology studies are needed to identify the complete range of possible neuropathologic changes; once identified, many of these changes can be better defined by specialized techniques, such as immunohistochemistry, to confirm cell types involved. Sometimes, when neurotoxicity... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169326 Sun, 21 Aug 2011 23:00:00 +0100 5169326 http://www.medworm.com/index.php?rid=5169325&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%3D21859886%26dopt%3DAbstract Authors: Bodié K, Gagne GD, Sramek MK, Desmond DJ, Abel SJ, Fagerland JA Abstract During baseline evaluation prior to a preclinical safety study, a 10-month-old male pure-bred Beagle dog was found to have marked thrombocytopenia (6 × 103 platelets [PLT]/µL) associated with a mean platelet volume (MPV) of 17.9 fL. Tests for Rickettsia rickettsii, Ehrlichia canis, and Borrelia burgdorferi were negative. Buccal bleeding time was normal. Over 3 months, PLT were 4 to 141 × 103 PLT/µL, and MPV was 11.4 to 25.1 fL; however, PLT were <50 × 103 PLT/µL and MPV was >16 fL during most of this period. Antinuclear antibody (ANA) and anti-PLT antibody tests were negative. Genotyping for the presence of a beta 1-tubulin mutation demonstrated the normal wild-type gene. Treatment with p... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169325 Sun, 21 Aug 2011 23:00:00 +0100 5169325 http://www.medworm.com/index.php?rid=5169324&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%3D21859887%26dopt%3DAbstract Authors: Ponce R Abstract International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S9 is the first international regulatory guidance document devoted to a specific therapeutic area, highlighting its importance in harmonizing regulatory expectations for the nonclinical development of therapeutics designed to treat advanced cancer. ICH S9 successfully outlines the core requirements for the nonclinical development of novel oncology therapeutics, and the unique risk-benefit considerations for expediting drug development to treat these most grievous diseases. However, development companies and regulatory agencies have had limited opportunity to apply this guidance, so our collective experience in developing therapeutics ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5169324 Sun, 21 Aug 2011 23:00:00 +0100 5169324 http://www.medworm.com/index.php?rid=5078841&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%3D21768270%26dopt%3DAbstract This study shows that macrophages exhibiting different immunophenotypes and distributions participate in post-BD injury fibrosis associated with myofibroblasts expressing various mesenchymal cytoskeletons. PMID: 21768270 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5078841 Sun, 17 Jul 2011 23:00:00 +0100 5078841 http://www.medworm.com/index.php?rid=5078840&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%3D21768271%26dopt%3DAbstract Authors: Song Y, Li X, Wang L, Rojanasakul Y, Castranova V, Li H, Ma J Nanomaterials are increasingly being used for commercial purposes. However, concerns about the potential risks of exposure to humans have been raised. We previously reported unusual pulmonary disease and death in a group of patients with occupational exposure to spray paint. However, the nanoparticle and chemical composition of the exposure was not fully described. The present study aimed to isolate and identify the nanoparticles observed in the patients' biopsies and report the potential deleterious effects to human lungs using electron microscopy. Using electron microscopy and energy dispersive x-ray analysis, silica nanoparticles were identified and characterized mainly in macrophages, pulmonary microvessels, vas... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5078840 Sun, 17 Jul 2011 23:00:00 +0100 5078840 http://www.medworm.com/index.php?rid=5029579&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%3D21747121%26dopt%3DAbstract Authors: Jokinen MP, Lieuallen WG, Boyle MC, Johnson CL, Malarkey DE, Nyska A The heart is increasingly recognized as a target for toxicity. As studies in laboratory rodents are commonly used to investigate the potential toxicity of various agents, the identification and characterization of lesions of cardiotoxicity is of utmost importance. Although morphologic criteria have been established for degenerative myocardial lesions in rats and mice, differentiation of spontaneously occurring lesions from toxin-induced or toxin-related lesions remains difficult. A retrospective light microscopic evaluation was performed on the hearts of F344 rats and B6C3F(1) mice from National Toxicology Program (NTP) studies of six chemicals identified in the NTP database in which treatment-induced myocard... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5029579 Sun, 10 Jul 2011 23:00:00 +0100 5029579 http://www.medworm.com/index.php?rid=5029578&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%3D21747122%26dopt%3DAbstract Authors: Yoshida M, Takahashi M, Inoue K, Hayashi S, Maekawa A, Nishikawa A Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus-pituitary-gonadal axis and reproductive system in females. Some lesions are noted after maturation as delayed adverse effects. We investigated the characteristics and dose dependence of delayed effects using female rats neonatally exposed to diethylstilbestrol (DES). Female Donryu rats were subcutaneously injected with a single dose of DES of 0 (control), 0.15, 1.5, 15, 150, or 1,500 µg/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 µg/kg and some at 150 µg/kg showed abnormal morphologies in the genital tract, indicating they were androgenized befor... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5029578 Sun, 10 Jul 2011 23:00:00 +0100 5029578 http://www.medworm.com/index.php?rid=5029581&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%3D21734250%26dopt%3DAbstract Authors: Whitney KM, Schwartz Sterman AJ, O'Connor J, Foley GL, Garman RH Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparations of sciatic nerve from eighty-one control dogs in toxicity studies ranging from ten days to three months in duration. Spontaneous background changes included digestion chambers, foci of vacuolation, nerve fibers circumscribed by proliferating Schwann cells (bands of Büngner), and small foci of myelin aggregation. The latter accounted for 91% of the microscopic changes and were noted in all sections... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5029581 Tue, 05 Jul 2011 23:00:00 +0100 5029581 http://www.medworm.com/index.php?rid=5029580&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%3D21734251%26dopt%3DAbstract Authors: McKee JS, Gass JH Four groups of ten male and ten female rats each were treated intravenously with saline, 400 mg/kg/day of a commercially available injectable acetaminophen formulation, or 400 mg/kg/day of a new injectable acetaminophen formulation with (aged) or without (fresh) impurities daily for fourteen days. Gross observations of the mucosal surface of the stomachs from treated rats included multifocal to diffuse pale, elevated foci confined to the nonglandular region of the stomach. Treatment-related histologic observations consisted of epithelial hyperplasia and hyperkeratosis of the nonglandular mucosa of the stomach. The epithelial hyperplasia was characterized by a thickened epithelium, frequently accompanied by the development of undulations at the basement membra... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=5029580 Tue, 05 Jul 2011 23:00:00 +0100 5029580 http://www.medworm.com/index.php?rid=4984867&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%3D21705744%26dopt%3DAbstract Authors: Gill S, Kavanagh M, Barker M, Weld M, Vavasour E, Hou Y, Cooke GM Furan is a heterocyclic organic compound formed during heat treatment for processing and preservation of various types of food. Rodent studies have previously shown that furan is a hepatocarcinogen. Those studies were conducted over a high dose range, which induced tumors at nearly 100% incidence at all doses. This ninety-day gavage study in mice was conducted to extend the dose to a lower range (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg body weight [bw] per day) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects, including those affecting clinical biochemistry, hematology, tissue morphology, and histopathology. The liver was the primary target organ with ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984867 Thu, 23 Jun 2011 23:00:00 +0100 4984867 http://www.medworm.com/index.php?rid=4984868&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%3D21677315%26dopt%3DAbstract Authors: Wisler JA, Afshari C, Fielden M, Zimmermann C, Taylor S, Carnahan J, Vonderfecht S Seven novel and potent Raf small molecule kinase inhibitors (C1-7) were evaluated in seven-day oral repeat dose rat toxicity studies. All compounds tested induced hyperplasia in multiple tissues. Consistently affected was stratified squamous epithelium at a number of sites and transitional epithelium of urinary bladder and kidney. A seven-day time course study in rats showed morphologic evidence of epithelial proliferation in the nonglandular stomach within four to five hours after a single dose of C-1. Similar indications of cellular proliferation were observed in the urinary bladder by day 2 and in the heart, kidney, and liver by day 3. Transcriptional evidence of proliferation in the urinary ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984868 Tue, 14 Jun 2011 23:00:00 +0100 4984868 http://www.medworm.com/index.php?rid=4984870&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%3D21670166%26dopt%3DAbstract Authors: Arias-Loza PA, Hu K, Frantz S, Dienesch C, Bayer B, Wu R, Ertl G, Pelzer T The role of estrogens during myocardial ischemia has been extensively studied. However, effects of a standard hormone replacement therapy including 17β-estradiol (E2) combined with medroxyprogesterone acetate (MPA) have not been assessed, and this combination could have contributed to the negative outcomes of the clinical studies on hormone replacement. We hypothesized that adding MPA to an E2 treatment would aggravate chronic heart failure after experimental myocardial infarction (MI). To address this issue, we evaluated clinical signs of heart failure as well as left ventricular (LV) dysfunction and remodeling in ovariectomized rats subjected to chronic MI receiving E2 or E2 plus MPA. After eight wee... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984870 Sun, 12 Jun 2011 23:00:00 +0100 4984870 http://www.medworm.com/index.php?rid=4984869&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%3D21670167%26dopt%3DAbstract Authors: Ogata K, Kushida M, Miyata K, Sukata T, Yamada T, Uwagawa S, Kawamura S Teratomas commonly occur in the testis and ovary, whereas in the uterus they are rare. The authors report findings for a mass detected in the uterus of a 26-week-old mouse in a colony of C57BL/6 bred in their laboratory. The mass was located in the endometrium and protruded into the lumen. Histopathologically, it consisted of abnormal diploblastic or triploblastic tissues. Bone with a growth plate and myeloid cells, as well as cartilage, was mainly observed. It also included melanocytes, exocrine gland-like cells, striated muscle, and neuron-like cells. While these tissues were accompanied by extensive necrosis, all of them were well differentiated and lacked features of malignancy, such as invasion and me... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984869 Sun, 12 Jun 2011 23:00:00 +0100 4984869 http://www.medworm.com/index.php?rid=4984874&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%3D21636695%26dopt%3DAbstract Authors: Menke AL, Spitsbergen JM, Wolterbeek AP, Woutersen RA The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals s... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984874 Wed, 01 Jun 2011 23:00:00 +0100 4984874 http://www.medworm.com/index.php?rid=4984873&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%3D21666102%26dopt%3DAbstract Authors: Morton D, Alden CL PMID: 21666102 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984873 Tue, 31 May 2011 23:00:00 +0100 4984873 http://www.medworm.com/index.php?rid=4984872&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%3D21666103%26dopt%3DAbstract Authors: Sistare FD, Morton D, Alden C, Christensen J, Keller D, Jonghe SD, Storer RD, Reddy MV, Kraynak A, Trela B, Bienvenu JG, Bjurström S, Bosmans V, Brewster D, Colman K, Dominick M, Evans J, Hailey JR, Kinter L, Liu M, Mahrt C, Marien D, Myer J, Perry R, Potenta D, Roth A, Sherratt P, Singer T, Slim R, Soper K, Fransson-Steen R, Stoltz J, Turner O, Turnquist S, van Heerden M, Woicke J, Degeorge JJ Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result amon... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984872 Tue, 31 May 2011 23:00:00 +0100 4984872 http://www.medworm.com/index.php?rid=4984871&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%3D21666104%26dopt%3DAbstract Authors: Ward JM, Thoolen B PMID: 21666104 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4984871 Tue, 31 May 2011 23:00:00 +0100 4984871 http://www.medworm.com/index.php?rid=4885241&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%3D21628716%26dopt%3DAbstract Authors: Kushida M, Kamendulis LM, Peat TJ, Klaunig JE The C57BL/6 mouse strain (or derivation of this strain) is used as a background for many transgenic mouse models. This strain has a relatively low susceptibility to chemically induced hepatocarcinogenesis compared with other commonly used experimental mouse strains. In the present study, the authors treated C57BL/6 mice with 25, 50, and 75 mg/kg of diethylnitrosamine (DEN) for 4 or 8 weeks by intraperitoneal injection to investigate the dose-response pattern of preneoplastic and neoplastic lesion formation in the liver. DEN induced preneoplastic lesions and cytokeratin 8/18-positive foci in a dose-dependent manner. In the 75 mg/kg for 8 weeks treatment group, hepatocellular adenoma, cholangioma and hemangioma, and cytokeratin 19-po... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4885241 Mon, 30 May 2011 23:00:00 +0100 4885241 http://www.medworm.com/index.php?rid=4885240&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%3D21628717%26dopt%3DAbstract Authors: Pereira ME, Macri NP, Creasy DM The rabbit is occasionally used for inhalation and intranasal safety assessment studies, but there are no detailed descriptions of the anatomy or histology of the rabbit nose. To address this deficit, the nasal cavities of thirty-two control adult rabbits were sectioned and examined to provide mapping of the main epithelial types and histological structures present within the cavity and turbinates. Four levels of the nasal cavity were prepared and examined using anatomic landmarks. Level I was sectioned immediately posterior to the incisors, Level II at the first palatal ridge, Level III immediately anterior to the first upper premolar teeth, and Level IV immediately anterior to the first upper molar. Level I was lined predominantly by squamous ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4885240 Mon, 30 May 2011 23:00:00 +0100 4885240 http://www.medworm.com/index.php?rid=4885239&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%3D21628718%26dopt%3DAbstract Authors: Felice BR, Wright TL, Boyd RD, Butt MT, Pfeifer RW, Pan J, Ruiz JA, Heartlein MW, Calias P Recombinant human idursulfase, an intravenous enzyme replacement therapy indicated for treatment of somatic symptoms of mucopolysaccharidosis II (Hunter syndrome), is anticipated to have minimal benefit for the cognitive impairment associated with the severe phenotype. Because intrathecal (IT) administration of enzyme replacement therapy for other lysosomal enzyme disorders has shown efficacy in animal models, an IT formulation of idursulfase (idursulfase-IT) and a drug-delivery device (subcutaneous port connected to a lumbar IT catheter) were developed for treating central nervous system (CNS) involvement. In this chronic safety study, cynomolgus monkeys were dosed weekly with IV idursu... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4885239 Mon, 30 May 2011 23:00:00 +0100 4885239 http://www.medworm.com/index.php?rid=4885238&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%3D21628719%26dopt%3DAbstract Authors: Vezzali E, Manno RA, Salerno D, Oberto G, Nyska A, Ramot Y The Göttingen minipig is one of the nonrodent species recommended by various regulatory authorities for safety assessment of drugs in preclinical studies. In such studies, knowledge of background pathology is critical in order to evaluate the potential renal toxicity. In the present study, the authors report 4 cases of glomerulonephritis out of 154 microbiologically defined Göttingen minipigs microscopically evaluated in preclinical studies. One animal required early sacrifice because of general poor health, and an additional animal died spontaneously. Histopathological evaluation revealed renal lesions in all 4 animals, exhibiting membranous or membranoproliferative glomerulonephritis at different stages, accompanie... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4885238 Mon, 30 May 2011 23:00:00 +0100 4885238 http://www.medworm.com/index.php?rid=4833844&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%3D21571946%26dopt%3DAbstract Authors: Hoenerhoff MJ, Pandiri AR, Lahousse SA, Hong HH, Ton TV, Masinde T, Auerbach SS, Gerrish K, Bushel PR, Shockley KR, Peddada SD, Sills RC Hepatocellular carcinoma (HCC) is an important cause of morbidity and mortality worldwide. Although the risk factors of human HCC are well known, the molecular pathogenesis of this disease is complex, and in general, treatment options remain poor. The use of rodent models to study human cancer has been extensively pursued, both through genetically engineered rodents and rodent models used in carcinogenicity and toxicology studies. In particular, the B6C3F1 mouse used in the National Toxicology Program (NTP) two-year bioassay has been used to evaluate the carcinogenic effects of environmental and occupational chemicals, and other compounds. Th... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833844 Thu, 12 May 2011 23:00:00 +0100 4833844 http://www.medworm.com/index.php?rid=4833849&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%3D21558466%26dopt%3DAbstract Authors: Holland T, Holland C It is a common problem to distinguish a minor treatment change from background variation, especially when establishing no observed effect levels. Toxicological histopathologists use a wide range of methods at the microscope for comparing groups to help them form their opinions. Although the data produced by these methods can be subjective, all of these methods produce data that can be formally analyzed to give an objective, probabilistic result, provided the observations are unbiased. Other important experimental disciplines make extensive use of completely subjective data to produce objective results, for example, clinical trials using patients' symptoms. It is argued here that pathological experimental data too should be analyzed before an expert opinion... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833849 Mon, 09 May 2011 23:00:00 +0100 4833849 http://www.medworm.com/index.php?rid=4833848&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%3D21558467%26dopt%3DAbstract In conclusion, the no-observed adverse effect level for FOB and general toxicity was 200 mg/kg following gavage administration of ST-20 for up to 15 consecutive days. PMID: 21558467 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833848 Mon, 09 May 2011 23:00:00 +0100 4833848 http://www.medworm.com/index.php?rid=4833847&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%3D21558468%26dopt%3DAbstract Authors: Herman E, Knapton A, Rosen E, Zhang J, Estis J, Agee SJ, Lu QA, Todd JA, Lipshultz SE Cardiac troponins have proved to be reliable blood biomarkers for identifying a variety of myocardial alterations in humans and animals. Recently, an ultrasensitive cTnI assay (Erenna IA) has been used to demonstrate increases in baseline cTnI resulting from drug-induced myocardial injury in rats, dogs, and monkeys, as well as to document baseline cTnI ranges in Sprague-Dawley (SD) rats. The present study was initiated to use the Erenna cTnI assay to further document baseline cTnI concentrations in normal control animals from multiple strains, including SD, Spontaneous Hypertensive (SHR), Wistar, Wistar-Kyoto (WKY), and Fisher strains. Baseline cTnI concentrations were quantified in all rats ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833847 Mon, 09 May 2011 23:00:00 +0100 4833847 http://www.medworm.com/index.php?rid=4833846&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%3D21558469%26dopt%3DAbstract Authors: Schwartz JA, Solomon JA, Henkelman K, Leininger JR, Iverson WO A single, solid, yellow-white thymic mass was found at necropsy of a two-year-old female cynomolgus macaque from a four-week, repeat-dose toxicity and immunogenicity study. Microscopically, the mass was multilobular and well encapsulated, surrounded by a thick connective tissue capsule, and composed of dense sheets of elongate or spindle-shaped cells and large cystic cavities separated by thick connective tissue stroma. Normal thymus was adjacent to the mass, but it was compressed. Within the mass were abundant interspersed Hassall's corpuscles; individual and small clusters of mature, small lymphocytes; scattered eosinophils; large areas of necrosis; focal mineralization; and cholesterol clefts. An interesting fea... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833846 Mon, 09 May 2011 23:00:00 +0100 4833846 http://www.medworm.com/index.php?rid=4833845&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%3D21558470%26dopt%3DAbstract Authors: Hvid H, Fels JJ, Kirk RK, Thorup I, Jensen HE, Hansen BF, Oleksiewicz MB High doses of insulin and the insulin analog AspB10 have been reported to increase mammary tumor incidence in female rats likely via receptor-mediated mechanisms, possibly involving enhanced IGF-1 receptor activation. However, insulin and IGF-1 receptor functionality and intracellular signaling in the rat mammary gland in vivo is essentially unexplored. The authors investigated the effect of a single subcutaneous dose of 600 nmol/kg human insulin or IGF-1 on Akt and ERK1/2 phosphorylation in rat liver, colon, and mammary gland. Rat tissues were examined by Western blotting and immunohistochemistry by phosphorylation-specific antibodies. Insulin as well as IGF-1 caused Akt phosphorylation in mammary epithe... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833845 Mon, 09 May 2011 23:00:00 +0100 4833845 http://www.medworm.com/index.php?rid=4833851&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%3D21551027%26dopt%3DAbstract Authors: Tsubota K, Kanki M, Noto T, Shiraki K, Takeuchi A, Nakatsuji S, Seki J, Oishi Y, Matsumoto M, Nakayama H Evaluation of ovarian toxicity requires an understanding of the physiological changes related to the estrous cycle in the ovary. The authors investigated the transitional gene expression profile of ovulatory follicles in rats that show normal estrous cyclicity. Ovaries were collected at 10:00 and 22:00 on the proestrus day and at 10:00 on the estrus day. Ovarian follicles or early corpora lutea were isolated using laser microdissection, and extracted total RNA was analyzed using microarray technology. Clustering analysis revealed four different expression patterns: transient up- or down-regulation only at 22:00 on the proestrus day (pattern 1), up- or down-regulation only a... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833851 Wed, 04 May 2011 23:00:00 +0100 4833851 http://www.medworm.com/index.php?rid=4833850&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%3D21551028%26dopt%3DAbstract Authors: Zabka TS, Fielden MR, Garrido R, Tao J, Fretland AJ, Fretland JL, Albassam MA, Singer T, Kolaja KL During routine safety evaluation of RO2910, a non-nucleoside reverse transcriptase inhibitor for HIV infection, histopathology findings concurrent with robust hepatocellular induction occurred in multiple organs, including a unique, albeit related, finding in the pituitary gland. For fourteen days, male and female rats were administered, by oral gavage vehicle, 100, 300, or 1000 mg/kg/day of RO2910. Treated groups had elevated serum thyroid-stimulating hormone and decreased total thyroxine, and hypertrophy in the liver, thyroid gland, and pituitary pars distalis. These were considered consequences of hepatocellular induction and often were dose dependent and more pronounced in ma... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4833850 Wed, 04 May 2011 23:00:00 +0100 4833850 http://www.medworm.com/index.php?rid=4781074&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%3D21519041%26dopt%3DAbstract Authors: Yokouchi Y, Imaoka M, Sayama A, Sanbuissho A A seven-year-old female cynomolgus monkey had a mass in the left ovary with metastasis to the lung and the right ovary. The mass of these organs showed three different characteristics, and its immunohistochemical profiles were consistent with embryonal carcinoma (EC), choriocarcinoma (CC), and epithelioid trophoblastic tumor (ETT). The EC was characterized with sheets and glandlike structures with large pleomorphic, single-nucleated epithelial cells that were immunohistochemically positive for α-fetoprotein, octamer-4, and CD30, and with multinucleated giant cells resembling syncytiotrophoblasts. The CC also represented biphasic proliferation of the cytotrophoblast positive for cytokeratin 7 (CK7), which showed negative immunoreact... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4781074 Wed, 04 May 2011 20:45:02 +0100 4781074 http://www.medworm.com/index.php?rid=4781075&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%3D21498792%26dopt%3DAbstract In conclusion, ENU induces retinal degeneration in adult mice that is characterized by photoreceptor cell apoptosis. PMID: 21498792 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4781075 Thu, 14 Apr 2011 23:00:00 +0100 4781075 http://www.medworm.com/index.php?rid=4676421&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%3D21422259%26dopt%3DAbstract Authors: Hubbs AF, Mercer RR, Benkovic SA, Harkema J, Sriram K, Schwegler-Berry D, Goravanahally MP, Nurkiewicz TR, Castranova V, Sargent LM Advances in chemistry and engineering have created a new technology, nanotechnology, involving the tiniest known manufactured products. These products have a rapidly increasing market share and appear poised to revolutionize engineering, cosmetics, and medicine. Unfortunately, nanotoxicology, the study of nanoparticulate health effects, lags behind advances in nanotechnology. Over the past decade, existing literature on ultrafine particles and respirable durable fibers has been supplemented by studies of first-generation nanotechnology products. These studies suggest that nanosizing increases the toxicity of many particulates. First, as size decre... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676421 Tue, 05 Apr 2011 10:15:08 +0100 4676421 http://www.medworm.com/index.php?rid=4676420&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%3D21422260%26dopt%3DAbstract Authors: Damsch S, Eichenbaum G, Looszova A, Lammens L, Feyen B, Bulck KV, Knight E, Kelley M, Tonelli A In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation. Since posterior nasal regions were most affected, with food material present within the inflammatory exudates, reflux and retrograde aspiration of irritant material (possibly stomach contents with test formulation) into the nasal cavity were suspected. Lowering the dose volume ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676420 Tue, 05 Apr 2011 10:15:08 +0100 4676420 http://www.medworm.com/index.php?rid=4676419&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%3D21422261%26dopt%3DAbstract Authors: Damsch S, Eichenbaum G, Tonelli A, Lammens L, Bulck KV, Feyen B, Vandenberghe J, Megens A, Knight E, Kelley M After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing. The absence of clear guidance and criteria for the identification and management of reflux-induced effects can limit the ability to properly interpret toxicity study results. The review presented herein includes an overview of experimental data from gavage studies in rats, in which reflux was observed, and provides a comprehensive analysis of the literature on r... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676419 Tue, 05 Apr 2011 10:15:08 +0100 4676419 http://www.medworm.com/index.php?rid=4676418&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%3D21422262%26dopt%3DAbstract This article describes how the integrated use of investigational tools represents a powerful approach for the early identification and characterization of cardiotoxicity in preclinical development. Cardiac changes were observed in the dog after long-term oral administration of casopitant, a neurokinin 1 receptor antagonist, developed for the treatment of depression and anxiety. Different approaches and sensitive biomarkers were used in a time-course study to investigate the onset, progression, and reversibility of the lesion. The integrated evaluation of cardiovascular parameters, electron microscopy, troponin I, and natriuretic peptide results highlighted any minimal early changes, allowing the full and deep characterization of the lesion. The outcome of this study was the driver for drug... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676418 Tue, 05 Apr 2011 10:15:08 +0100 4676418 http://www.medworm.com/index.php?rid=4676417&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%3D21422263%26dopt%3DAbstract In this study, we characterized the histopathological features of corpora lutea (CL) from EGME-treated rats and compared them with normal CL formation and regression. Normally cycling female Sprague-Dawley rats were treated with 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally on the morning of estrus and their ovaries were examined 1 (metestrus), 4 (estrus), 8 (estrus), or 12 (estrus) days later to observe the transition of BrdU-labeled cells within in the CL. CL at each time point of estrus stage were classified into 4 types: Type I (newly formed CL), Type II (mature CL), Type III (regressing CL), and Type IV (residual CL). CL almost fully regressed within 4 estrus cycles. In contrast, in female rats given EGME orally (30, 100, or 300 mg/kg for 2 or 4 weeks), luteal cells were hypertroph... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676417 Tue, 05 Apr 2011 10:15:08 +0100 4676417 http://www.medworm.com/index.php?rid=4676416&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%3D21422264%26dopt%3DAbstract Authors: Travlos GS, Hard GC, Betz LJ, Kissling GE The occurrence and severity of spontaneous chronic progressive nephropathy (CPN) in control male F344 rats as well as the frequency of treatment-related CPN exacerbation were histopathologically reevaluated. A series of 43 National Toxicology Program (NTP) 90-day toxicity studies comparing the influence of NIH-07 or NTP-2000 diets was examined. Relationships between the histopathologic findings at 90 days and renal tubule proliferative lesions recorded in subsequent 2-year bioassays for 24 chemicals were statistically analyzed. CPN lesions were observed in 100% of the control male rats regardless of diet, but CPN was more severe in control rats fed NIH-07. Approximately one-third of the 90-day studies demonstrated a treatment-related e... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676416 Tue, 05 Apr 2011 10:15:08 +0100 4676416 http://www.medworm.com/index.php?rid=4676415&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%3D21422265%26dopt%3DAbstract Authors: Holland T There are substantial differences between the information required in a diagnostic histopathology report and an experimental pathology report. A diagnostic report rests on the authority of the person issuing it, so there is less emphasis on the data and analysis on which the diagnosis is based being in the report. By contrast, an experimental report gains its authority from the integrity of the data and the objective analysis of that data. It is recommended that the current diagnostic reporting of the histopathology component of toxicological studies be changed to a more experimental report approach. PMID: 21422265 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676415 Tue, 05 Apr 2011 10:15:08 +0100 4676415 http://www.medworm.com/index.php?rid=4676414&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%3D21422266%26dopt%3DAbstract Authors: Schafer KA PMID: 21422266 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676414 Tue, 05 Apr 2011 10:15:08 +0100 4676414 http://www.medworm.com/index.php?rid=4676413&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%3D21422267%26dopt%3DAbstract Authors: Jortner B, Rogers-Cotrone T PMID: 21422267 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676413 Tue, 05 Apr 2011 10:15:08 +0100 4676413 http://www.medworm.com/index.php?rid=4676409&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%3D21444746%26dopt%3DAbstract In this report we outline the rationale for setting up this workshop series, summarize our experience, and suggest approaches for optimizing histopathology phenotyping for gene function discovery. PMID: 21444746 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676409 Sun, 27 Mar 2011 23:00:00 +0100 4676409 http://www.medworm.com/index.php?rid=4676411&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%3D21441227%26dopt%3DAbstract Authors: Stoltz JH, Huang Q, Stern J, Seidler R, Pack F, Knight B BILN 2061 is a potent, reversible inhibitor of hepatitis C virus NS3/NS4A serine protease. Early clinical proof of principle with the drug was offset by the results of subsequent safety studies in Rhesus monkeys revealing cardiotoxicity that featured myocardial vacuolation corresponding to mitochondrial swelling. Here we describe an investigation into the nature, onset, and reversibility of the lesion, and an assessment of potentially predictive biomarkers for the change. Rhesus monkeys were orally administered 1,000 mg/kg/day BILN 2061 and either necropsied after one, three, fourteen, or twenty-eight doses or afforded a ten-week recovery period. The results of electrocardiographic and plasma troponin I and T measurement... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676411 Fri, 25 Mar 2011 00:00:00 +0100 4676411 http://www.medworm.com/index.php?rid=4676410&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%3D21441228%26dopt%3DAbstract Authors: Holt SV, Wyspianska B, Randall KJ, James D, Foster JR, Wilkinson RW Autophagy is believed to be an important process during tumorgenesis, and in recent years it has been shown to be modulated in response to a number of conventional anticancer agents. Furthermore, the development of targeted small molecule inhibitors, such as those to the PI3K-AKT-mTOR pathway, has presented a molecular link between the disruption of this signalling cascade and the process of autophagy. The cellular consequence of stimulating or inhibiting autophagy in cancer cells is not completely understood, so it is important that this process be monitored, along with antiproliferative and apoptotic biomarkers, in the preclinical setting. The field of autophagy is still evolving, and there is a constantly c... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676410 Thu, 24 Mar 2011 00:00:00 +0100 4676410 http://www.medworm.com/index.php?rid=4676412&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%3D21430177%26dopt%3DAbstract This article outlines the changes and underlying rationale for modifications to the histopathological evaluation of the nervous system during toxicology and carcinogenesis studies conducted by the National Toxicology Program (NTP). In the past, routine evaluation of the nervous system was mostly limited to three sections of brain, and occasionally the spinal cord and peripheral nerves. Factors such as the increasing occurrence of human neurological diseases and associated economical cost burden, the role of unidentified environmental stressors in neurodegenerative disorders, multiple therapeutic drug-induced neuropathies noted in human clinical trials, and the exponential use of environmental chemicals with unknown neurotoxic potential necessitate a more extensive evaluation of the nervous... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4676412 Wed, 23 Mar 2011 00:00:00 +0100 4676412 http://www.medworm.com/index.php?rid=4615795&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%3D21378207%26dopt%3DAbstract This article reviews the neuroanatomical domains affected by several model neurotoxicants to illustrate the need for more comprehensive neurohistological evaluation during nonclinical development of novel compounds. The article also describes an easily executed, cost-effective method that uses a set number of evenly spaced coronal (cross) sections to accomplish this comprehensive brain assessment during nonclinical safety studies performed in rodents, dogs, and nonhuman primates. PMID: 21378207 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615795 Tue, 22 Mar 2011 05:30:03 +0100 4615795 http://www.medworm.com/index.php?rid=4615794&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%3D21378208%26dopt%3DAbstract Authors: Bradley AE, Keane K General session 4 of a 2010 scientific symposium sponsored jointly by the Society of Toxicologic Pathology and the International Federation of Societies of Toxicologic Pathologists considered the problem of primary neoplasms of the nervous system, especially the brain and spinal cord. Primary tumors of the nervous system account for a small but persistent fraction of cancers, occur disproportionately in juveniles, and are notoriously difficult to treat. This session explored new ideas and techniques with respect to the etiopathogenesis, diagnosis, and treatment of neural tumors with an emphasis on the translation of animal models of brain neoplasia and toxicology investigations for candidate therapeutic agents to the human situation. Additionally, this sess... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615794 Tue, 22 Mar 2011 05:30:03 +0100 4615794 http://www.medworm.com/index.php?rid=4615793&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%3D21378209%26dopt%3DAbstract Authors: Martin LJ Researchers used transgenic mice expressing enhanced-green fluorescent protein (eGFP) driven by either the glycine transporter-2 gene promoter to specifically visualize glycinergic interneurons or the homeobox-9 (Hb9) gene promoter to visualize motoneurons for assessing their vulnerabilities to excitotoxins in vivo. Stereotaxic excitotoxic lesions were made in adult male and female mouse lumbar spinal cord with the specific N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid (QA) and the non-NMDA ion channel glutamate receptor agonist kainic acid (KA). QA and KA induced large-scale degeneration of glycinergic interneurons in spinal cord. Glycinergic interneurons were more sensitive than motoneurons to NMDA receptor-mediated and non-NMDA glutamate receptor-me... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615793 Tue, 22 Mar 2011 05:30:03 +0100 4615793 http://www.medworm.com/index.php?rid=4615792&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%3D21378210%26dopt%3DAbstract Authors: PMID: 21378210 [PubMed - in process] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615792 Tue, 22 Mar 2011 05:30:03 +0100 4615792 http://www.medworm.com/index.php?rid=4615789&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%3D21411719%26dopt%3DAbstract Authors: Goulet F, Vachon P, Hélie P Eugenol has been shown to induce anesthesia in African clawed frogs (Xenopus laevis). The toxicity of eugenol, administered at anesthetic doses, was evaluated in Xenopus frogs with an average body weight of 28.2 ± 13.7 g. Frogs were immersed in 250 mL of an aqueous solution containing 350 µl/L of eugenol for ten minutes and received a single administration (group 1, twelve animals) or three consecutive daily administrations (group 2, twelve animals). In each group, six frogs were scheduled to be euthanized the following day (subgroup A) and the other six were scheduled to be euthanized after a one-week recovery period (subgroup B). Morphologic changes consistent with renal tubular apoptosis affecting distal tubules in the medulla were observed in... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615789 Wed, 16 Mar 2011 00:00:00 +0100 4615789 http://www.medworm.com/index.php?rid=4615788&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%3D21411720%26dopt%3DAbstract The objective was to determine the respiratory toxicity of MAP0004, orally inhaled dihydroergotamine (DHE), via inhalation for six months. Forty beagle dogs (twenty females, twenty males) were treated by nose-only inhalation for 182 days. Groups 2 through 5 received MAP0004 (mean doses: 0.045, 0.154, 0.44, 0.825 mg/kg); Group 1 received vehicle only. Groups 1 through 4 received single thirty-minute exposures, whereas Group 5 was exposed twice daily for thirty minutes. Toxicity was assessed from clinical observations, objective evaluations, and clinical and anatomical pathology. Systemic effects were scabbing of ear tips in Groups 3, 4, and 5 and excessive salivation and emesis, observed in Group 5. No changes were observed in the lungs in any dose group. Minimal treatment-related microscop... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615788 Wed, 16 Mar 2011 00:00:00 +0100 4615788 http://www.medworm.com/index.php?rid=4615787&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%3D21411721%26dopt%3DAbstract Authors: Aleem E, Nehrbass D, Klimek F, Mayer D, Bannasch P The molecular mechanisms underlying the development of hepatocellular carcinoma (HCC) are not yet fully understood. Preneoplastic foci of altered hepatocytes regularly precede HCC in various species. The predominant earliest type of foci of altered hepatocytes, the glycogen storage focus (GSF), shows an excess of glycogen (glycogenosis) in the cytoplasm. During progression from GSF to HCC, the stored glycogen is gradually reduced, resulting in complete loss in basophilic HCC. We have previously shown that in N-nitrosomorpholine-induced hepatocarcinogenesis, insulin receptor substrate (IRS-1) is strongly expressed in GSF and reduced during progression to HCC, thus correlating with the glycogen content. In the present study, we ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615787 Wed, 16 Mar 2011 00:00:00 +0100 4615787 http://www.medworm.com/index.php?rid=4615786&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%3D21411722%26dopt%3DAbstract In this study, we determine the effects of the hormonally active compounds, conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, and tamoxifen (TAM) on the myometrium of ovariectomized macaques. Immunoexpression of estrogen receptor-α (ERα), progesterone receptor (PR), and Ki-67 in the myometrium is assessed. We found no significant difference in ERα myometrial expression in the CEE, MPA, and CEE + MPA treatment groups, but there was a significant decrease in expression in animals administered TAM versus controls. Conjugated equine estrogen-, TAM-, and CEE + MPA-treated animals had significantly increased expression of PR in myometrial cells and there was no difference in PR expression in cells from MPA-treated animals versus control animals. Myometrial cell ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615786 Wed, 16 Mar 2011 00:00:00 +0100 4615786 http://www.medworm.com/index.php?rid=4615785&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%3D21411723%26dopt%3DAbstract Authors: Brechbiel JL, Ng JM, Curran T The advent of molecular targeted therapies offers the hope of therapeutic advance in the fight against cancer. However, this hope is tempered by recent findings that certain targeted therapies may have unique side effects. The Hedgehog (HH) pathway is a potential target for treatment of several cancers, including basal cell carcinoma and a subset of medulloblastoma. Recent clinical trials in adults have shown responses to HH pathway inhibition in both basal cell carcinoma and medulloblastoma. However, concerns have been raised about the use of HH pathway inhibitors in children because of the role the HH pathway plays in development. Indeed, young mice treated with the HH pathway inhibitor HhAntag developed severe bone defects, including premature ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615785 Wed, 16 Mar 2011 00:00:00 +0100 4615785 http://www.medworm.com/index.php?rid=4615791&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%3D21398559%26dopt%3DAbstract In conclusion, T-2 toxin exposure in rats induced degenerative lesions in articular cartilage similar to spontaneous OA, lending support to an etiologic role of mycotoxins in Kaschin-Beck Disease. T-2 toxin-induced degenerative joint disease may be a useful model of metabolic polyarticular OA. PMID: 21398559 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615791 Fri, 11 Mar 2011 00:00:00 +0100 4615791 http://www.medworm.com/index.php?rid=4615790&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%3D21398560%26dopt%3DAbstract This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expre... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4615790 Fri, 11 Mar 2011 00:00:00 +0100 4615790 http://www.medworm.com/index.php?rid=4500559&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%3D21300790%26dopt%3DAbstract Authors: Dunnick JK Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous background tumors including mammary gland tumors in female rats and liver tumors in male mice. Increased tumorigenicity in rodents exposed to goldenseal root powder may be due in part to the topoisomerase inhibition properties of berberine, a major alkaloid constituent in goldenseal, or its metabolite, berberrubine. In the clinic, use of topoisomerase-inhibiting agents has been associated with secondary tumor formation and inhibition in DNA repair processes. In ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4500559 Mon, 07 Feb 2011 00:00:00 +0100 4500559 http://www.medworm.com/index.php?rid=4500558&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%3D21300791%26dopt%3DAbstract Authors: Wancket L, Quist E, Net JL, Guzman R, Muravnick KB Amylase-resistant, periodic acid-Schiff (PAS)-positive inclusions were identified in the skeletal muscle of four of twenty-four purpose-bred beagle dogs from a routine toxicology study. Affected myofibers contained amorphous material filling up to 20% of the sarcoplasm that stained lightly basophilic with hematoxylin and eosin and was strongly PAS-positive with amylase resistance. Transmission electron micrographic examination of the inclusions revealed granular, non-membrane-bound, electron-dense material, consistent with polysaccharide. Although skeletal muscle inclusions with similar features have been reported in dogs in conjunction with systemic metabolic disorders and less often in muscle adjacent to nonmyogenic sarcomas... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4500558 Mon, 07 Feb 2011 00:00:00 +0100 4500558 http://www.medworm.com/index.php?rid=4500557&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%3D21300792%26dopt%3DAbstract Authors: Reagan WJ, Irizarry A, Bounous D, Walker D, Travlos G, Ramaiah S, Bolliger AP, Poitout-Belissent F, Walter G This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant-induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used succes... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4500557 Mon, 07 Feb 2011 00:00:00 +0100 4500557 http://www.medworm.com/index.php?rid=4500560&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%3D21297067%26dopt%3DAbstract Authors: Young JK, Hall R, Strauss V, O'Brien P The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4500560 Fri, 04 Feb 2011 00:00:00 +0100 4500560 http://www.medworm.com/index.php?rid=4442309&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%3D21270422%26dopt%3DAbstract Authors: Jamadagni S, Jamadagni P, Upadhyay S, Gaidhani S, Hazra J A unilateral non-metastatic embryonal carcinoma and teratoma of the testis was observed in a 12-week-old Swiss Albino mouse at the end of a 28-day repeated dose toxicity study. The teratocarcinoma almost completely replaced the parenchyma of the left testis. The tumor was composed of sheets and rosettes of primitive embryonal cells, anaplastic cells, skeletal muscle tissue, sebaceous gland tissue, keratinized stratified squamous epithelium, and ciliated cuboidal epithelium. The histomorphological characteristics of the tumor were reviewed and presented in this report. To the best of the authors' knowledge, this is the first report of spontaneous teratocarcinoma of testis in the Swiss Albino strain of mice. PMID: 212... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4442309 Wed, 26 Jan 2011 00:00:00 +0100 4442309 http://www.medworm.com/index.php?rid=4442308&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%3D21270423%26dopt%3DAbstract This article provides observations on the features of sponsor-contract research organization communication that will achieve the best quality pathology report based on our collective experience. Information on the test article and any anticipated findings should be provided, and initial slide examination should be done with knowledge of treatment group (but may be followed by blinded review of target tissues to determine no-effect levels). Only a pathologist should write or revise the pathology report or the pathology section of the overall study report. To address concerns related to undue sponsor influence, comments by sponsors should be presented as suggestions rather than directives. Adversity should be defined for each finding by the study pathologist, but the no-observed adverse effe... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4442308 Wed, 26 Jan 2011 00:00:00 +0100 4442308 http://www.medworm.com/index.php?rid=4442307&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%3D21270424%26dopt%3DAbstract Authors: Glinghammar B, Andersson U, Hellmold H The dual peroxisome-proliferator-activated receptor (PPAR) α/γ agonist tesaglitazar has been shown to produce fibrosarcomas in rats. Here, the authors studied morphology, proliferation, differentiation, and inflammation markers in adipose tissue from rats exposed to 1, 3, or 10 µmol/kg tesaglitazar for 2 or 12 weeks, including recovery groups (12 weeks treatment followed by 12 weeks recovery), and 3 or 10 µmol/kg tesaglitazar for 24 weeks. Subcutaneous white and brown fat revealed reversible dose-related histopathological alterations and after 12 and 24 weeks developed areas of thickened skin (fatty lumps). There was a dose-dependent increase in proliferation of interstitial cells in white and brown fat as shown by increased mitotic i... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4442307 Wed, 26 Jan 2011 00:00:00 +0100 4442307 http://www.medworm.com/index.php?rid=4442310&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%3D21257999%26dopt%3DAbstract In conclusion, P407 is taken up by the liver mostly through endocytosis by LSECs and Kupffer cells. PMID: 21257999 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4442310 Fri, 21 Jan 2011 00:00:00 +0100 4442310 http://www.medworm.com/index.php?rid=4378201&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%3D21212254%26dopt%3DAbstract Authors: Hale SL, Andrews-Jones L, Jordan WH, Jortner BS, Boyce RW, Boyce JT, Switzer RC, Butt MT, Garman RH, Jensen K, Krinke G, Little PB This session at the 2010 joint symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) explored modern neuropathology methods for assessing the neurotoxicologic potential of xenobiotics. Conventional techniques to optimally prepare and evaluate the central and peripheral neural tissues while minimizing artifact were reviewed, and optimal schemes were set forth for evaluation of the nervous system during both routine (i.e., general toxicity) studies and enhanced (i.e., specialized neurotoxicity) studies. Stereology was introduced as the most appropriate means of examin... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4378201 Thu, 06 Jan 2011 00:00:00 +0100 4378201 http://www.medworm.com/index.php?rid=4378202&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%3D21196527%26dopt%3DAbstract Authors: Weber K, Garman R, Germann PG, Hardisty JF, Krinke G, Millar P, Pardo I Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granula... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4378202 Fri, 31 Dec 2010 00:00:00 +0100 4378202 http://www.medworm.com/index.php?rid=4378204&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%3D21189316%26dopt%3DAbstract Authors: Johanson C, Stopa E, McMillan P, Roth D, Funk J, Krinke G Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway ("nexus") of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolatio... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4378204 Tue, 28 Dec 2010 00:00:00 +0100 4378204 http://www.medworm.com/index.php?rid=4378203&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%3D21189317%26dopt%3DAbstract Authors: Willis CL The blood-brain barrier (BBB) is the regulated interface that mediates selective transcellular transport of nutrients and essential components from the blood into the brain parenchyma. Many neurodegenerative diseases including stroke, multiple sclerosis, rheumatoid arthritis, and AIDS dementia exhibit loss of BBB integrity. Despite the increasing body of evidence for the involvement of glia in maintaining the BBB, few studies have addressed glial/endothelial/extracellular matrix interactions. A chemically induced astrocyte lesion provides a noninvasive model to study reversible BBB dysfunction in vivo. Blood-brain barrier integrity was assessed with fluorescent dextran tracers (3-70 kDa) and magnetic resonance imaging, in parallel with confocal and electron microscop... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4378203 Tue, 28 Dec 2010 00:00:00 +0100 4378203 http://www.medworm.com/index.php?rid=4289522&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%3D21177526%26dopt%3DAbstract Authors: Montine TJ Diseases that commonly cause dementia in the general population are Alzheimer's disease, microvascular brain injury, and Lewy body disease. Each of these is a chronic disease with latent, prodromal, and dementia stages. Here I present outcomes from validated neuropathologic assessments and cerebrospinal fluid biomarkers to estimate the prevalence of the latent stage of diseases that commonly contribute to the dementia syndrome. The latent stage of diseases that commonly cause dementia is highly prevalent in the adult population, highlighting the need for prevention strategies and longitudinal studies. PMID: 21177526 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4289522 Tue, 21 Dec 2010 00:00:00 +0100 4289522 http://www.medworm.com/index.php?rid=4289507&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%3D21177527%26dopt%3DAbstract This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an over... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4289507 Tue, 21 Dec 2010 00:00:00 +0100 4289507 http://www.medworm.com/index.php?rid=4237538&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%3D21131603%26dopt%3DAbstract Authors: Baker DC, Brassard J The continuing education course "Hemostasis" provided a comprehensive review of hemostasis and selected perturbations of the underlying processes as well as an assessment of hemostasis in animal models and preclinical testing environments. The session began with a review of the current state of understanding of hemostasis and how the waterfall or cascade of activation has transformed to the current cell-based, membrane-associated sequence of highly regulated events. The specific mechanisms of drug-induced thrombocytopenia were then presented, followed by a discussion of the relationships of coagulation and platelets in inflammation and cancer metastasis and platelet activity. Evaluation of hemostasis and platelet function in animals and especially in the e... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237538 Fri, 03 Dec 2010 00:00:00 +0100 4237538 http://www.medworm.com/index.php?rid=4237544&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%3D21119050%26dopt%3DAbstract Authors: Arezzo JC, Litwak MS, Zotova EG The evaluation of neurotoxic damage involves a unique set of challenges. Vulnerable structures, such as neocortex, hippocampus, spinal cord, and peripheral nerve are complex and sharply differentiated; deficits can result from insults to one or more element(s) in the system (e.g., myelin, axon, soma, synapse, or glia). In-life assessment of neurotoxic damage is complicated by the relative inaccessibility of structures in the brain and spinal cord, and recovery is severely limited. Histopathology and electrophysiology represent two of the most commonly used and valuable techniques in this field. This review outlines the strengths and limitations of these procedures and focuses on circumstances in which findings from these measures are dissociated... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237544 Tue, 30 Nov 2010 00:00:00 +0100 4237544 http://www.medworm.com/index.php?rid=4237543&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%3D21119051%26dopt%3DAbstract Authors: Garman RH The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cy... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237543 Tue, 30 Nov 2010 00:00:00 +0100 4237543 http://www.medworm.com/index.php?rid=4237542&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%3D21119052%26dopt%3DAbstract Authors: Johnson GA, Badea A, Jiang Y Magnetic resonance imaging (MRI), now common in the clinical domain, has been adapted for use by the neuropathologist by increasing the spatial resolution over 100,000 times what is common in human clinical imaging. This increase in spatial resolution has been accomplished through a variety of technical advances-higher magnetic fields, more sensitive receivers, and clever encoding methods. Magnetic resonance histology (MRH), that is, the application of MRI to study tissue specimens, now makes three-dimensional imaging of the fixed brain in the cranium routine. Active staining (perfusion fixation with a paramagnetic contrast agent) has allowed us to reduce the scan time by more than 8 times over earlier methods. The result is a three-dimensional iso... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237542 Tue, 30 Nov 2010 00:00:00 +0100 4237542 http://www.medworm.com/index.php?rid=4237541&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%3D21119053%26dopt%3DAbstract The objective was to consider issues that dictate the choice of animal models for neuropathology-based studies used to investigate neurological diseases and novel therapeutic agents to treat them. In some cases, no animal model exists that recapitulates the attributes of the human disease (e.g., fibromyalgia syndrome). Alternatively, numerous animal models are available for other conditions, so an essential consideration is selecting the most appropriate experimental system (e.g., Alzheimer's disease). New technologies (e.g., genetically engineered rodent models) promise the opportunity to generate suitable animal models for syndromes that currently lack any in vivo animal model, while in vitro models offer the opportunity to evaluate xenobiotic effects in specific neural cell populations.... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237541 Tue, 30 Nov 2010 00:00:00 +0100 4237541 http://www.medworm.com/index.php?rid=4237540&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%3D21119054%26dopt%3DAbstract Authors: Gale AJ The goal of this review is to briefly summarize the two primary pathways of hemostasis, primary hemostasis and secondary hemostasis, as well as to summarize anticoagulant mechanisms and fibrinolysis. In addition, this review will discuss pathologies of hemostasis and the mechanisms of the various drugs that are available to impact these pathways to prevent either thrombosis or bleeding. While many of the main drugs that are used to treat disorders of hemostasis have been used for decades, greater understanding of hemostasis has led to development of various new drugs that have come onto the market recently or are close to coming onto the market. Thus, improved understanding of hemostasis continues to lead to benefits for patients. PMID: 21119054 [PubMed - as suppli... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237540 Tue, 30 Nov 2010 00:00:00 +0100 4237540 http://www.medworm.com/index.php?rid=4237539&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%3D21119055%26dopt%3DAbstract Authors: Bolon B, Bradley A, Butt M, Jensen K, Krinke G, Mellon R Neuropathology analyses as end points during nonclinical efficacy and toxicity studies are challenging and require trained personnel and particular equipment to achieve optimal results. Accordingly, many regulatory agencies have produced explicit guidelines for designing and performing neuropathology assessments for nonclinical studies. This compilation of international regulatory guidance for toxicologic neuropathology end points represents a set of criteria recommended for general toxicity studies and specialized neurotoxicity studies that should facilitate the efforts of individuals who plan, perform, analyze, and report neuropathology evaluations in nonclinical toxicity studies. PMID: 21119055 [PubMed - as suppli... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4237539 Tue, 30 Nov 2010 00:00:00 +0100 4237539 http://www.medworm.com/index.php?rid=4176952&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%3D21078918%26dopt%3DAbstract Authors: Jones TS, Holland EC Malignant glial tumors are the most aggressive and difficult to treat neoplasms arising in the brain. More than 22,000 people in the United States are diagnosed with a malignant glioma annually, and most will die within the first two years from diagnosis. Traditionally, gliomas have been categorized based solely on tumor histological features. However, expression studies have found that molecular signatures can be used to categorize these tumors into subclasses that more effectively predict patient outcome. The heterogeneity between tumors as well as within individual tumors makes understanding the molecular aspects of tumorigenesis extremely important. Several genetically engineered mouse models (GEMMs) of glioma have been developed that recapitulate the ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4176952 Mon, 15 Nov 2010 00:00:00 +0100 4176952 http://www.medworm.com/index.php?rid=4176951&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%3D21078919%26dopt%3DAbstract Introduction and Commentary: "Toxicologic Neuropathology"--and a Whole Lot More! The 2010 Joint STP/IFSTP International Symposium on Toxicologic Pathology. Toxicol Pathol. 2010 Nov 15; Authors: Bolon B, Funk K, Sills R PMID: 21078919 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4176951 Mon, 15 Nov 2010 00:00:00 +0100 4176951 http://www.medworm.com/index.php?rid=4176950&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%3D21078920%26dopt%3DAbstract Authors: Bolon B, Bradley A, Garman R, Krinke G Investigations in toxicologic neuropathology are complex undertakings because of the intricate spatial and temporal diversity in the anatomic, functional, and molecular organization of the central and peripheral nervous systems. This compilation of toxicologic neuropathology resources has been designed to consolidate a broad range of useful neurobiology, neuropathology, and neurotoxicology resources in a single reference. This collection will increase familiarity with the basic knowledge, skills, and tools required for the proficient practice of toxicologic neuropathology and should help to improve the analysis and interpretation of pathology data sets from neural tissues in toxicology studies. PMID: 21078920 [PubMed - as supplied by ... Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4176950 Mon, 15 Nov 2010 00:00:00 +0100 4176950 http://www.medworm.com/index.php?rid=4176949&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%3D21078921%26dopt%3DAbstract This article is from a presentation at the 2010 STP/IFSTP Symposium on Neuropathology. The organization and basic structure of the peripheral nervous system is reviewed. Examples of toxicant-induced peripheral nerve injury such as neuronopathy, axonopathy, and myelinapathy are discussed, as are contemporary methods for examination of these tissues. PMID: 21078921 [PubMed - as supplied by publisher] (Source: Toxicologic Pathology) Toxicologic Pathology journals http://www.medworm.com/rss/comments.php?id=4176949 Mon, 15 Nov 2010 00:00:00 +0100 4176949