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. 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.
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(1) Considerable evidence has accumulated that the molecular target of general anesthetics in the central nervous system is the GABA(A) receptor, the major mediator of inhibitory synaptic transmission. This receptor is actually a family of ligand-gated chloride channel proteins, each a heteropentameric membrane-spanning structure. (2) Regional variation in anesthetic actions on the central nervous system may parallel a corresponding regional variation in pharmacological subtypes of GABA(A) receptors. These result from differential regional expression of approximately 18 subunit genes. (3) Receptors of varying subunit composition show differential sensitivity to GABA, modulatory drugs, and biological regulatory mechanisms. Regional variation in allosteric modulation of GABA(A) receptor binding and function can be reconstituted in certain recombinant receptor subunit combinations expressed in heterologous cells. (5) Differential sensitivity to anesthetics for various GABA(A) receptor subunits also allows the use of the chimeric and site-directed mutagenesis approach in attempting to define domains of the protein which participate in the binding and actions of anesthetics.