Toxicology mechanisms and methods
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Toxicol. Mech. Methods · Sep 2011
Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.
Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. ⋯ Vapor concentrations increased with time in the dermal and ocular exposure systems but were stable with varying amounts of applied SM. A dermal deposition estimation study was also conducted. Deposited volumes increased with exposure time.
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Toxicol. Mech. Methods · Oct 2010
Acute secretory cell toxicity and epithelial exfoliation after smoke inhalation injury in sheep: an electron and light microscopic study.
Smoke inhalation injury promotes exfoliation of the upper airway columnar epithelium. Tracheal tissues from sheep 30 min after smoke exposure show intact epithelial areas, areas of epithelial disruption with loss of columnar cells and areas denuded of columnar cells. In intact areas detaching ciliated cells can be seen raised above the apical surface. ⋯ All detaching cells were identified as ciliated cells. These studies show that the acute effects of inhalation injury include selective secretory cell toxicity which is associated with loss of junctional adhesion mechanisms and displacement of ciliated cells. Improved understanding of acute hypersecretory responses and epithelial integrity after exposure to toxic agents may improve understanding of epithelial fragility in airway disease.
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Toxicol. Mech. Methods · Sep 2009
Evaluation of nine oximes on in vivo reactivation of blood, brain, and tissue cholinesterase activity inhibited by organophosphorus nerve agents at lethal dose.
The capability of several oximes (HI-6, HLö7, MMB-4, TMB-4, carboxime, ICD 585, ICD 692, ICD 3805, and 2-PAM) to reactivate in vivo AChE inhibited by the nerve agents sarin, cyclosarin, VX, or VR in blood, brain regions, and peripheral tissues in guinea pigs was examined and compared. Animals were injected subcutaneously with 1.0 LD(50) of sarin, cyclosarin, VR, or VX, and treated intramuscularly 5 min later with one of these compounds. Toxic signs and lethality were monitored, and tissue AChE activities were determined at 60 min after nerve agent. ⋯ There was no difference in the AChE reactivating potency between the dichloride and dimethanesulfonate salts of HI-6. AChE inhibited by sarin was the most and cyclosarin the least susceptible to oxime reactivation. Overall, MMB-4 appeared to be, among all oximes tested, the most effective in vivo AChE reactivator against the broadest spectrum of nerve agents.
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Toxicol. Mech. Methods · Jan 2009
Silica-induced TNF-alpha and TGF-beta1 expression in RAW264.7 cells are dependent on Src-ERK/AP-1 pathways.
The cytokines secreted by lung macrophages have been shown to play a critical role in the pathogenesis of silicosis, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) are prominent cytokines in silicosis, but the underlying mechanism remains to be determined. The aim of the present study was to investigate the roles of Src-mitogen-activated protein kinase (MAPKs)/activator protein-1 (AP-1) signaling pathways in silica-induced TNF-alpha and TGF-beta1 expression in macrophage cells (RAW264.7). It was found that silica activated Src, p38 kinase, and extracellular signal-regulated kinase (ERK) in RAW264.7 cells. ⋯ Dominant negative mutant c-Jun (TAM67) inhibited silica-induced AP-1 DNA binding activity and downregulated the TNF-alpha and TGF-beta1 expression. In addition, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by silica. Based on these findings, it was conclude that Src-ERK/AP-1 signaling pathways are involved in the TNF-alpha and TGF-beta1 expression induced by silica in macrophages.
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Toxicol. Mech. Methods · Jan 2005
Human exposure to selamectin from dogs treated with revolution: methodological consideration for selamectin isolation.
This study was undertaken to determine selamectin residue in dog's blood and in gloves worn while petting dogs after Revolution application. Revolution contains the active ingredient selamectin (a semisynthetic avermectin), which controls endoparasites and ectoparasites, including adult fleas, flea eggs, ticks, heartworms, ear mites, and sarcoptic mange in dogs, for 30 days. Revolution was applied topically on a group of six adult house hold dogs (240 mg selamectin/dog). ⋯ No selamectin residue was detected in the glove extracts after the fifth week. In spite of selamectin's binding to the sebaceous glands of the skin, gloves contained significant transferable residue. Thus, these findings suggest that repeated exposure to selamectin can pose potential health risks, especially to veterinarians, veterinary technologists, dog trainers/handlers, and pet owners.