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Distribution and development of nicotinic acetylcholine receptor subtypes in the optic tectum of Rana pipiens.

Acetylcholine allows the elicitation of visually evoked behaviors mediated by the frog optic tectum, but the mechanisms behind its effects are unknown. Although nicotinic acetylcholine receptors (nAChRs) exist in the tectum, their subtype has not been assessed. By using quantitative autoradiography, we examined the binding of [(3)H]cytisine and [(125)I]alpha-bungarotoxin in the laminated tectum. In mammalian systems, these radioligands bind with high affinity to alpha4 nAChR subunits and alpha7 nAChR subunits, respectively. [(3)H]Cytisine demonstrated high specific binding in adult frogs in retinorecipient layer 9, intermediate densities in layer 8, and low binding in layers 1-7 of the tectum. [(3)H]Cytisine binding was significantly higher in the tecta of adults than in those of tadpoles. Lesioning the optic nerve for 6 weeks decreased [(3)H]cytisine binding in layers 8/9 by 70+/-1%, whereas 6-month lesions decreased binding by 76+/-3%. Specific binding of [(125)I]alpha-bungarotoxin in adults was present only at intermediate levels in tectal layers 8 and 9, and undetectable in the deeper tectal layers. However, the nucleus isthmi, a midbrain structure reciprocally connected to the tectum, exhibited high levels of binding. There were no significant differences in tectal [(125)I]alpha-bungarotoxin binding between tadpoles and adults. Six-week lesions of the optic nerve decreased tectal [(125)I]alpha-bungarotoxin binding by 33+/-10%, but 6-month lesions had no effect. The pharmacokinetic characteristics of [(3)H]cytisine and [(125)I]alpha-bungarotoxin binding in the frog brain were similar to those demonstrated in several mammalian species. These results indicate that [(3)H]cytisine and [(125)I]alpha-bungarotoxin identify distinct nAChR subtypes in the tectum that likely contain non-alpha7 and alpha7 subunits, respectively. The majority of non-alpha7 receptors are likely associated with retinal ganglion cell terminals, whereas alpha7-containing receptors appear to have a different localization.

Alkaloids↗

Tonazocine mesylate in postoperative pain patients: a double-blind placebo controlled analgesic study.

One hundred-fifty post-operative adult patients with moderate to severe pain were enrolled into this analgesic efficacy study comparing single doses of tonazocine mesylate, a new mixed agonist-antagonist opioid analgesic, with morphine. The patients were randomly assigned to five treatment groups: tonazocine mesylate 2, 4, 8 mg; morphine sulfate 10 mg and a placebo group. The results showed mean total pain relief scores for tonazocine 4 mg were nearly identical with that of morphine sulfate 10 mg while 8 mg of tonazocine were superior to 10 mg of morphine. All the active medication groups were superior to the placebo group (P less than 0.02) for both pain intensity and pain relief. Relative potency determined by the dose response indicates that 3.2 mg of tonazocine is equivalent to 10 mg of morphine. Drowsiness was the main adverse reaction seen in all active treatment groups. Tonazocine mesylate appears to be a potent analgesic with promising clinical usefulness and warrants further study.

Adolescent↗

Examples of evolution of microstructure in ceramics and composites.

In this article we describe a number of studies involving the direct observation of microstructural evolution. In general these investigations were carried out to establish the mechanistic paths involved. The materials studied range from fibers being evaluated for use in high-temperature ceramic composites to energetic materials used as propellants. In particular we discuss the room temperature imaging of materials difficult to image by conventional means and the use of the chamber atmosphere to influence microstructural evolution. Imaging of hydroxyapatite formed by chemical means is briefly described as an example of a difficult microstructure. Microstructural evolution during calcium aluminate cement hydration relies on the chamber atmosphere to control moisture loss from the hydrating specimens. In some instances microstructural evolution with heating occurred independently of the chamber atmosphere. Grain growth in PZT films formed by sol-gel processes depends strongly on temperature but does not appear to depend on the chamber atmosphere. This is also the case for the combustion of nitroamine propellants in that their combustion does not depend on access to an external source of oxygen. In other studies, the chamber atmosphere played an indirect role in determining microstructure. However, the mechanistic path driving microstructural evolution in copper-based inks used as conductive paths on electronic substrates is atmosphere dependent. These inks are formulated from copper powder, glass, and an organic binder, and the interaction of the binder with an oxidizing atmosphere allows it to be burned out before significant interaction occurs between the copper powder and the glass. Finally, the microstructural variations during the oxidation of structural composites at high temperature were used to allow assessments of their likely failure mechanisms.

Animals↗

Development of a soil extraction procedure for ecotoxicity characterization of energetic compounds.

The acetonitrile-sonication extraction method (US EPA Method 8330) associated with aquatic-based toxicity tests was examined to study the ecotoxicity of energetic substances in soil. Three studies were carried out: (1) toxicological characterization of different energetic substances to select a representative toxicant and to validate the choice of bioassays; (2) choice of an appropriate solvent to transfer acetonitrile extracts to the bioassay incubation media; and (3) optimization of Method 8330 using soil samples spiked with the toxicant. Initial studies indicated that pure 2,4,6-trinitrotoluene (TNT) was toxic to Vibrio fischeri [Microtox; IC50 (15 min) of 4.2 microM], whereas RDX was less toxic (IC20 = 181 microM) and HMX was not toxic up to its limit of water solubility (< 22 microM). Selected pure TNT metabolites were less toxic than TNT. Similar results were found using the 96-h Selenastrum capricornutum growth inhibition test. The toxicity of pure TNT in different solvents (acetonitrile, acetone, and DMSO) and that from Method 8330-extracted TNT-spiked soil samples were compared to TNT dissolved in water. Data indicated that DMSO was the most appropriate solvent to transfer the acetonitrile extracts. A modified Method 8330 may be used in conjunction with bioassays and chemical analyses to examine the ecotoxicity of soils contaminated with energetic substances.

Acetone↗