High performance laser diode bars with aluminum-free active regions.

We present operating and lifetest data on 795 and 808 nm bars with aluminum-free active regions. Conductively cooled bars operate reliably at CW power outputs of 40 W, and have high efficiency, low beam divergence, and narrow spectra. Record CW powers of 115 W CW are demonstrated at 795 nm for 30% fill-factor bars mounted on microchannel coolers. We also review QCW performance and lifetime for higher fill-factor bars processed on identical epitaxial material.

In situ mapping of community-level cellular response with catalytic microbiosensors.

Chemotaxis, the migration of cells in the direction of a spatial chemical gradient, is important in disease progression, microbial ecology, and bioremediation. The ability to map chemoattractant gradients and the corresponding cellular growth and motility patterns is essential to the study of chemotaxis. Microelectrodes and microbiosensors have the potential to measure chemoattractant gradients with high spatial resolution. In this study, Clark-type amperometric microelectrodes and microbiosensors were used to measure solute concentrations gradients generated by a chemotactic band of Escherichia coli in a semi-solid gel. A computerized image analysis system was used to simultaneously measure the cellular concentration profile across the chemotactic band. The experimental results compared favorably with a mathematical model of solute and cell transport in the gel. Scanning electron micrographs (SEM) of micro(bio)sensor tips taken after 6 months of use showed evidence of degradation, including adhesion of foreign particles to the glass body, the adhesion of a small gel capsule to the sensor tip, and separation of the bio-interface from the tip. A needle-type microbiosensor was constructed to better protect the tip and hence increase the ruggedness of the microbiosensors.

Cholinergic agents: antinociception without morphine type dependence in rats.

We have confirmed the work of others showing that loss in body weight is a predictable and consistent sign of opiate withdrawal in rats. Rats that were treated chronically with either oxotremorine or physostigmine displayed no weight loss or other signs of opiate-like withdrawal when the drugs were withdrawn. Furthermore, there was no difference in weight loss between morphine dependent rats substituted with saline and those substituted with either cholinergic drug. However, we did observe an increased mortality among rats substituted with a cholinergic agent compared with saline. Rats infused with a mixture of morphine plus oxotremorine or morphine plus physostigmine showed less weight loss, but not fewer behavioral signs, after the end of the infusion than rats treated only with morphine. It is concluded that the cholinergic agents did not cause a morphine-like physical dependence themselves, but appeared to antagonize to some extent the development or manifestation of opiate dependence.

The new selective D2-dopamine receptor antagonist raclopride--pharmacokinetics, safety and tolerability in healthy males.

Raclopride, a new potential antipsychotic drug, with high selectivity and affinity for central D2-dopamine receptors, was in this first human study administered to 8 healthy male volunteers in single oral doses from 0.1 to 16 mg. Two subjects, known to be slow metabolizers of debrisoquine, were also included. Pharmacokinetics, safety, tolerability, and effect on plasma prolactin levels were evaluated. The maximum plasma concentrations of raclopride (Cmax) and the area under the raclopride curve vs time (AUC) increased proportionally with dose. No deviant kinetic parameters were seen in the slow debrisoquine metabolizers. Only minor deviations in biochemical and physiological safety parameters were found. Raclopride was well tolerated by all subjects at doses up to 8 mg but not at 16 mg because of akathisia. No other extrapyramidal side-effects were recorded. The drug induced a rapid and transient increase of plasma prolactin concentrations.

Patterns of service use and treatment involvement of methadone maintenance patients.

Although methadone maintenance is an effective treatment for opiate addiction, variations in treatment outcome are evident. These variations may be explained in part by the rehabilitative experiences of patients as reflected in their use of collateral services. This study examined service involvement of 409 methadone maintenance patients at four clinics in order to identify the types of services used and the extent to which potentially rehabilitative services were used. Aside from welfare, there was a strikingly low level of service utilization. Even when services were used, the levels of this use were so low as to be virtually ineffective. These findings regarding treatment and social service utilization suggest that there may not be any attempt to match service provision with patient needs for services. A more rational approach to matching patient needs and available services is thus called for.

Dihydroxylated metabolites of cannabinol formed by rat liver in vitro.

Cannabinol (CBN) was metabolized in vitro by a 10,000 g supernatant from rat liver. After removal of unchanged CBN and its monohydroxylated metabolites four dihydroxylated metabolites were isolated. By nuclear magnetic resonance and mass spectrometry the compounds were identified as 1'',7-dihydroxy-CBN. Side chain hydroxylation occurred predominantly at C-4'' anc C-3''.

Acidic in vivo metabolites of cannabinol isolated from rat faeces.

Six acidic metabolites were isolated from rat faeces and identified by gas chromatographymass spectrometry and proton magnetic resonance. Cannabinol-7-oic acid was the most abundant acidic metabolite isolated. Others present in decreasing order of prominence were 1"-hydroxy-, 4"-hydroxy-, 3"-hydroxycannabinol-7-oic acid, cannabinol-3"-one-7-oic acid and 2"-hydroxycannabinol-7-oic acid.

Neutral in vivo metabolites of cannabinol isolated from rat faeces.

The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono-oxygenated and dioxygenated CBN metabolites have been identified. In the mono-oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7-hydroxy-CBN, 4''-hydroxy-CBN, 1''-hydroxy-CBN, 2''-hydroxy-CBN, 3''-hydroxy-CBN, 5''-hydroxy-CBN and CBN-7-al. In the dihydroxylated metabolite series only 1'',7-dihydroxy-CBN and 4'',7-dihydroxy-CBN were found with the former as the more prominent metabolite.

Metabolism of delta1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism.

The metabolism of (-)-delta1-tetrahydrocannabinol (delta1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-delta1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC was also present together with small amounts of 6alpha-hydroxy-delta1-THC and 6beta-hydroxy-delta1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6beta-hydroxy-delta1-THC and 6alpha-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of delta1-THC.

In situ mutagenesis and chemotactic selection of microorganisms in a diffusion gradient chamber.

A new method has been developed to rapidly generate and select microbial strains having increased resistance to an inhibitory compound. The method combines in situ mutagenesis with use of a continuous gradient of the inhibitor to sort cells according to their resistance levels. Microbial chemotaxis is induced to accelerate the selection process. The method was used to develop a strain of E. coli having a feedback-resistant DAHP synthase enzyme. An unsteady-state mathematical model of the process has been developed. The model, that can reproduce key trends observed experimentally, was used to explore the effects of chemotaxis on the efficiency of the selection process.

Chromatographic separation of cannabinoids and their monooxygenated derivatives.

delta1-Tetrahydrocannabinol, delta6-tetrahydrocannabinol, cannabinol, cannabidiol and several of their monooxygenated derivatives have been separated from each other by a combination of liquid, thin-layer and gas chromatography. Retention volumes (on Sephadex LH-20), Rf values and retention times can be recorded, and may provide guidance in the separation and identification of these known cannabinoids.

Glucuronic acid conjugate of delta 1-tetrahydrocannabinol identified in the urine of man.

A delta 1-tetrahydrocannabinol (delta 1-THC) metabolite has been identified as an O-glucuronide of delta 1-THC in the human urine after oral administration of delta 1-THC. The metabolite was present in small amounts and its identity was confirmed by comparison of its mass spectrum to that of a reference compound.