Toxicologic pathology
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Toxicologic pathology · Jan 2012
ReviewEcological impacts of the deepwater horizon oil spill: implications for immunotoxicity.
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. ⋯ The assessment of injuries, damages, and restoration options for the DWH spill is ongoing. Although petroleum and the polycyclic aromatic hydrocarbon component of oils are known to affect the immune systems of aquatic organisms and wildlife, immunotoxicity is not typically assessed during oil spills and has not been a focus of the DHW assessment. The effects of oil spill contaminants on immune responses are variable and often exposure dependent, but immunotoxic effects seem likely from the DHW spill based on the reported effects of a variety of oils on both aquatic and wildlife species.
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Session 1 of the 2010 STP/IFSTP Joint Symposium on Toxicologic Neuropathology, titled "Fundamentals of Neurobiology," was organized to provide a foundation for subsequent sessions by presenting essential elements of neuroanatomy and nervous system function. A brief introduction to the session titled "Introduction to Correlative Neurobiology" was provided by Dr. Greg Hall (Eli Lilly and Company, Indianapolis, IN). Correlative neurobiology refers to considerations of the relationships between the highly organized and compartmentalized structure of nervous tissues and the functioning within this system.
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beta-cyclodextrin (beta-CD) and other cyclodextrins (CDs) have utility for solubilizing and stabilizing drugs; however, some are nephrotoxic when administered parenterally. A number of workers have attempted to identify, prepare, and evaluate various CD derivatives with superior inclusion complexation and maximal in vivo safety for various biomedical uses. A systematic study led to SBE-beta-CD (Captisol), a polyanionic variably substituted sulfobutyl ether of beta-CD, as a non-nephrotoxic derivative and HP-beta-CD, a modified CD developed by Janssen. ⋯ The pharmacokinetics, tissue distribution, and cellular effects of some representative CDs, including SBE-beta-CD and HP-beta-CD, are reviewed. The safety profiles of CDs are discussed, with emphasis on the biological effects of some CDs on the gastrointestinal tract, kidney, and reproduction and development and the carcinogenic potential of CDs. In addition, human experience with CD derivatives, specifically SBE-beta-CD and HP-beta-CD, indicates that these two CDs are well tolerated in humans and have no adverse effects on the kidneys or other organs following either oral or intravenous administration.
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Toxicologic pathology · Jan 1999
ReviewCorrelation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1.
ISIS 2302 is a phosphorothioate oligodeoxynucleotide with a sequence complementary to the mRNA of human intercellular adhesion molecule 1 (ICAM-1). Hybridization of ISIS 2302 to the mRNA inhibits expression of the ICAM-1 protein in response to inflammatory stimuli. A murine active antisense oligonucleotide, ISIS 3082, has been used for in vivo pharmacology studies and has anti-inflammatory activity in models of organ transplant rejection, ulcerative colitis, and collagen-induced arthritis at doses ranging from 0.03 to 5 mg/kg. ⋯ In monkeys, high concentrations of oligonucleotide caused a transient increase in clotting times and activation of the alternative complement pathway. All toxicities associated with ISIS 2302 were reversible and occurred at doses well above those required for pharmacologic activity or currently used in clinical trials. In addition, there has been no evidence of genetic toxicity associated with ISIS 2302, and no changes in reproductive performance, fertility, or fetal development have been noted in animals treated with ISIS 2302 or ISIS 3082.
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Toxicologic pathology · Jan 1996
ReviewStructure and function of sinusoidal lining cells in the liver.
The hepatic sinusoid harbors 4 different cells: endothelial cells (100, 101), Kupffer cells (96, 102, 103), fat-storing cells (34, 51, 93), and pit cells (14, 107, 108). Each cell type has its own specific morphology and functions, and no transitional stages exist between the cells. These cells have the potential to proliferate locally, either in normal or in special conditions, that is, experiments or disease. ⋯ The number and cytotoxicity of pit cells can be considerably enhanced with biological response modifiers, such as Zymosan or interleukin 2 (8). Pit cell proliferation occurs within the liver, but recent evidence indicates that blood large granular lymphocytes develop into pit cells in 2 steps involving high- and low-density pit cells (88). Kupffer cells control the motility, adherence, viability, and cytotoxicity of pit cells (89), whereas cytotoxicity against tumor cells is synergistically enhanced (80, 81).