Toxicology letters
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A number of the autoimmune rheumatic diseases are associated with environmental factors, drugs and chemicals. The often non-specific presentation of these diseases makes early diagnosis difficult. The availability of serological markers such as autoantibodies improves diagnostic ability when taken in context with the presenting clinical features. This review focuses on some of the major autoimmune rheumatic diseases and their associated autoantibody markers.
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One of the major dose-limiting toxicities induced by antimicrotubule antitumor agents such as vinca alkaloids and taxanes is peripheral neuropathy. The neurotoxicity of TZT-1027 (a dolastatin 10 derivative antimicrotubule agent) was thus assessed using the animal models for antimicrotubule agent-induced neurotoxicity. ⋯ Despite the neuropathologic evidence such as myelinated axonal and fiber degeneration in the peripheral nerves and in the sensory tracts of the spinal cord following the treatment with vincristine or paclitaxel, no drug-induced alteration was observed in the TZT-1027 groups. Although there are reports that some other dolastatin derivatives with antimicrotubule activity showed no neurotoxic potential in humans, the present study represents the first demonstration in experimental animals that a dolastatin derivative has no, or at least a lower, neurotoxic potential compared to other antimicrotubule agents.
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Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of colorectal cancer. Moreover, the NSAID sulindac reduces the number and size of polyps in patients with familial adenomatous polyposis. The mechanisms of these effects of NSAIDs are not known but several lines of evidence suggest the involvement of the inhibition of the inducible isoform of prostaglandin H synthase (known as COX-2). Specific COX-2 inhibitors, showing an improved profile of gastrointestinal safety vis-à-vis conventional NSAIDs, provide interesting tools to probe the COX-2 dependence of the apparent protection against colorectal cancer associated with the use of NSAIDs.
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(1) The discovery of the non-anaesthetics has provided a unique opportunity for using novel modelling techniques to study the molecular mechanisms of anaesthesia. (2) We have selected the molecular similarity approach to investigate the importance of three-dimensional molecular fields, such as geometric shape and electrostatic potential, in (a) determining whether an agent exhibits anaesthetic activity and (b) in determining the in vivo potencies of active agents. (3) The results to date are both provocative and highly promising.
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1. General anesthesia is achieved by anesthetic action in the central nervous system (CNS). 2. ⋯ The extent to which anesthetic action in the brain influences the spinal cord probably varies among anesthetics. Furthermore, anesthetics can indirectly influence the brain by their actions within the spinal cord, i.e. by modulating ascending transmission of sensory information.