Simple procedure for measuring the pharmacodynamics and analgesic potential of lipoxygenase inhibitors.

A model is described for determining the pharmacodynamics of inhibitors of arachidonate metabolism in mice. Bioavailability and selectivity were assessed by ex vivo RIA of TXB2, LTB4, and 12-HETE from ionophore-challenged blood. Inhibition of LTB4 and 12-HETE was measured using a single LTB4 RIA, following extraction and separation of these eicosanoids from plasma. Separation on cyanopropyl mini-columns yielded hexane/ether and methanol fractions, which contained 12-HETE and LTB4, respectively. Analgesic efficacy was measured by inhibition of phenylbenzoquinone-induced abdominal constriction. The NSAIDs, indomethacin ibuprofen, flurbiprofen, and benoxaprofen, were analgesic and selective cyclo-oxygenase inhibitors. BW775C was also analgesic, but inhibited cyclo-oxygenase, 5-lipoxygenase and 12-HETE formation. Other in vitro 5-lipoxygenase inhibitors, NDGA, quercetin, and nafazatrom, were inactive in vivo, although NDGA reduced abdominal constrictions. The results indicate that this model has utility in determining the mechanism/selectivity of action and analgesic potential of 5-lipoxygenase inhibitors.

Investigating the MESA (multipoint electrotactile speech aid): the transmission of segmental features of speech.

Four normal-hearing young adults have been extensively trained in the use of a tactile speech-transmission system. Subjects were tested in the recognition of various phonetic elements including vowels, and stop, nasal, and fricative consonants under three receiving conditions; visual reception alone (lipreading), tactile reception alone, and tactile plus visual reception. Subjects were artificially deafened using earplugs and white noise and all speech tokens were presented live voice. Analysis of the data demonstrates that the tactile transform enables receivers to achieve excellent recognition of vowels in CVC context and the consonantal features of voicing and nasality. This, in combination with high recognition of vowels and the consonantal feature place of articulation through visual receptors, leads to recognition performance in the combined condition (visual plus tactual) which far exceeds either reception condition in isolation.