Toxicology letters
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Asbestos deposits have been used locally by the rural inhabitants of Central and Southeastern Anatolia for domestic purposes for many years. Mineralogical analysis revealed that tremolite is the most prominent asbestos type found in the region. There is in addition another mineral fiber found particularly in three villages located in the Cappadocian region of Central Anatolia (zeolite villages). ⋯ In zeolite villages malignant mesothelioma is responsible for more than 50% of the total deaths. A recent study showed that simian virus 40 is not a cofactor in the pathogenesis of environmental malignant mesothelioma in Turkey. An additional recent genetic-epidemiological study showed that there are some families, which are genetically predisposed to mesothelioma.
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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) 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.