Effects of acute and chronic morphine on rotational behavior in nigral-lesioned rats

Stimulation of mu-opioid receptors located on dopaminergic neurons in the striatum and the nucleus accumbens increases dopamine release, which may account for some of the behavioral effects of morphine. In this study, we examined the effects of acute and chronic morphine treatment on rotational behavior in rats with unilateral 6-hydroxydopamine dopamine (6-OHDA)-induced lesions of the nigrostriatal pathway. Rats receiving morphine acutely (0.3-10 mg/kg) did not show a significant bias toward contralateral or ipsilateral turning. Mini osmotic pumps dispensing morphine continuously (20-24 mg/kg/day) were implanted s.c. in these animals. This treatment induced tolerance to the behavioral depression produced by the highest dose of morphine (10 mg/kg) when it was given acutely. A slight but significant increase in ipsilateral turning occurred over the range of morphine doses examined. The effects of morphine on rotational behavior are slight, and do not correlate well with the reported increase in locomotor activity or extraneural dopamine in the striatum that are produced by doses of morphine similar to the ones tested in this study.     

Diol diricinoleates from dihaloalkanes

A series of alkanediol diricinoleates was prepared by heating ricinoleic acid with triethylamine and dibromo- or dichloroalkanes containing 2 to 10 carbon atoms. As expected, the dibromides react more rapidly than the dichlorides. This method of esterification avoids the side reaction of estolide formation which occurs when ricinoleates are prepared by direct esterification or transesterification. The products are high molecular weight diols which should be useful in the preparation of polyurethanes. Presented at the AOCS Meeting, San Francisco April 1969. W. Utiliz. Res. Dev. Div., ARS, USDA.     

The effect of heat treatments on the semiconductor properties of a commercially electrodeposited manganese dioxide

The temperature dependence of d.c. conductivity and thermoelectric power has been studied for a series of thermally treated samples of an electrodeposited, microcrystalline, γ-phase MnO₂. Measurements were made on samples compacted at 3.86 × 10⁵ KN/m². Measurements of a.c. impedance up to 50 MHz were made on the powder samples to test for particle homogeneity. The results indicated that a hopping electron transport model was probably appropriate for these samples and that the majority carriers were electrons, possibly ionised from donor sites provided by oxygen deficiency. Conductivity, surprisingly, was found to increase in an oxygen environment and it is suggested that oxygen adsorption greatly enhances the electron mobility. The d.c. conductivity and thermoelectric power were found to be strongly dependent on sample outgassing temperature. The former reached a maximum at about 320 °C, the latter became less negative with increasing outgassing temperature. It is tentatively proposed that carrier density and “surface” mobility increased as terminal OH groups forming strong traps on manganese sites were removed by thermal treatment. Measurements of a.c. impedance on samples outgassed at 35 °C and 365 °C displayed dispersion around 20 MHz indicative of a high resistance surface skin possibly due to a hydroxylated and reduced surface respectively.     

Generalised efficiency curve for step-recovery-diode frequency multipliers

The optimised efficiencies of step-recovery-diode frequency multipliers for various diode parameters and orders of multiplication have been obtained using an analogue-computer simulation. It has been shown possible to determine these efficiencies as functions of a single figure of merit of the multiplier, the one curve being valid for all conditions investigated.     

Structures revealed in zone refined aluminum by tritium decoration

A method is described for decorating structures in solid aluminum by precipitation of hydrogen onto them. Radioactive hydrogen is employed so that the deposition sites can be revealed by the use of autoradiographic techniques. The study was conducted with zone refined aluminum, and the primary structure that was revealed was that remaining after directional solidification during the last zone pass. The tritium was added to the specimen at 600°C and its precipitation was brought about by quenching the sample. As little as 0.05 ppm of tritium was sufficient to reveal complex structures in the cast metal that are attributed to association of unidentified residual impurity atoms with low angle subgrain boundaries that are thought to have resulted from polygonization occurring immediately behind the advancing solid-liquid interface. Wide-angle grain boundaries were also decorated. New structures were introduced by various levels of strain that accompanied different upsetting operations. Grain and subgrain boundaries that developed during strain anneals were “antisites” for hydrogen deposition. This opposite behavior is attributed to the absence of impurity atoms in these “new” boundaries. An explanation for the behavior of hydrogen in aluminum is given in terms of the condensation of vacancies vs their loss to vacancy sinks. These phenomena are shown to be involved in the enlargement of hydrogen-filled pores in aluminum.     

Applications of contaminant fate and bioaccumulation models in assessing ecological risks of chemicals: a case study for gasoline hydrocarbons

Mass balance models of chemical fate and transport can be applied in ecological risk assessments for quantitative estimation of concentrations in air, water, soil, and sediment. These concentrations can, in turn, be used to estimate organism exposures and ultimately internal tissue concentrations that can be compared to mode-of-action-based critical body residues that induce toxic effects. From this comparison, risks to the exposed organism can be evaluated. To demonstrate the use of fate models in ecological risk assessment, we combine the EQuilibrium Criterion (EQC) environmental fate model with a simple screening level biouptake model for three representative organisms: a bird, a mammal, and a fish. This effort yields estimates of internal body concentrations that can be compared with levels known to elicit toxic effects. As an illustration, we present an analysis of 24 hydrocarbon components of gasoline that differ in properties but are assumed to elicit toxicity by a common narcotic mode of action. Results demonstrate that differences in chemical properties and mode of entry into the environment lead to profound differences in the efficiency of transport from emission to target biota. We discussthe implications of these results and draw attention to the insights gained about regional fate and ecological risks associated with gasoline. This approach is suitable for assessing single chemicals or mixtures that have similar modes of action. We conclude that the model-based methodologies presented are widely applicable for screening level ecological risk assessments that support effective chemicals management.     

Design and implementation of a hands-free electrolarynx device controlled by neck strap muscle electromyographic activity

The electrolarynx (EL) voice prosthesis is widely used, but suffers from the inconvenience of requiring manual control. Therefore, a hands-free EL triggered by neck muscle electromyographic (EMG) activity was developed (EMG-EL). Signal processing circuitry in a belt-mounted control unit transforms EMG activity into control signals for initiation and termination of voicing. These control signals are then fed to an EL held against the neck by an inconspicuous brace. Performance of the EMG-EL was evaluated by comparison to normal voice, manual EL voice, and tracheo-esophageal (TE) voice in a series of reaction time experiments in seven normal subjects and one laryngectomy patient. The normal subjects produced voice initiation with the EMG-EL that was as fast as both normal voice and the manual EL. The laryngectomy subject produced voice initiation that was slower than with the manual EL, but faster than with TE voice. Voice termination with the EMG-EL was slower than normal voice for the normal subjects, but not significantly different than with the manual EL. The laryngectomy subject produced voice termination with the EMG-EL that was slower than with TE or manual EL. The EMG-EL threshold was set at 10% of the range of vocal-related EMG activity above baseline. Simulations of EMG-EL behavior showed that the 10% threshold was not significantly different from the optimum threshold produced through the process of error minimization. The EMG-EL voice reaction time appears to be adequate for use in a day-to-day conversation.     

Molecular basis of the constitutive activity and STI571 resistance of Asp816Val mutant KIT receptor tyrosine kinase

The receptor tyrosine kinase, KIT, displays activating mutations in the kinase domain, which are associated with various cancers. We have used homology modelling based on the crystal structures of the insulin receptor kinase in active and inactive conformations to predict the corresponding structures of the KIT kinase domain. We have prepared four KIT models, one each for the active and inactive conformations of the wild-type and of the Asp816Val mutant proteins. We have also placed ATP into the active conformations and the inhibitor, STI571, into the inactive conformations. All models have been fully energy minimised. The molecular modelling studies described here explain (i) why Asp816Val KIT is constitutively active, (ii) why the nature of the substituting amino acid at residue 816 is relatively unimportant, and (iii) why the Asp816Val substitution confers resistance to the KIT-inhibitory drug STI571. The models will be valuable for predicting other kinase inhibitory drugs that may be active on wild-type and mutant forms of KIT. During the course of this work, a crystal structure of the active conformation of the KIT kinase domain has been published. Our model of the active conformation of the Asp816Val mutant is strikingly similar to this crystal structure, whereas our model of the active conformation of the wild-type kinase domain of KIT differs from the crystal structure in some respects. The reasons for this apparent discrepancy are discussed.