New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites.

Synthetic cannabinoids (SCs) were initially developed as pharmacological tools to probe the endocannabinoid system and as novel pharmacotherapies, but are now highly abused. This is a serious public health and social problem throughout the world and it is highly challenging to identify which SC was consumed by the drug abusers, a necessary step to tie adverse health effects to the new drug\u27s toxicity. Two intrinsic properties complicate SC identification, their often rapid and extensive metabolism, and their generally high potency relative to the natural psychoactive Δ 9 -tetrahydrocannabinol in cannabis. Additional challenges are the lack of reference standards for the major urinary metabolites needed for forensic verification, and the sometimes differing illicit and licit status and, in some cases, identical metabolites produced by closely related SC pairs, i.e., JWH-018/AM-2201, THJ-018/THJ-2201, and BB-22/MDMB-CHMICA/ADB-CHMICA. We review current SC prevalence, establish the necessity for SC metabolism investigation and contrast the advantages and disadvantages of multiple metabolic approaches. The human hepatocyte incubation model for determining a new SC\u27s metabolism is highly recommended after comparison to human liver microsomes incubation, in silico prediction, rat in vivo, zebrafish, and fungus Cunninghamella elegans models. We evaluate SC metabolic patterns, and devise a practical strategy to select optimal urinary marker metabolites for SCs. New SCs are incubated first with human hepatocytes and major metabolites are then identified by high-resolution mass spectrometry. Although initially difficult to obtain, authentic human urine samples following the specified SC exposure are hydrolyzed and analyzed by high-resolution mass spectrometry to verify identified major metabolites. Since some SCs produce the same major urinary metabolites, documentation of the specific SC consumed may require identification of the SC parent itself in either blood or oral fluid. An encouraging trend is the recent reduction in the number of new SC introduced per year. With global collaboration and communication, we can improve education of the public about the toxicity of new SC and our response to their introduction

Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence of ionization type, sample preparation, and biofluid

AbstractThe purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-μg/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS

A superposition principle for Siegert resonant states

The utilization of the Siegert resonant states as a natural basis for the scattering process has been constrained by the lack of a convergent superposition formula. This paper presents such an expansion of the exact scattering wavefunction over the s-wave Siegert resonant states for finite range potentials. Any integral property of the scattering wavefunction can then be calculated from the resonances

Upward mobility of staff nurses

Thesis (M.S.)--Boston Universit

Critical Evaluation of Chemical Reaction Rates and Collision Cross Sections of Importance in the Earth's Upper Atmosphere and the Atmospheres of Other Planets, Moons, and Comets

We propose to establish a long-term program of critical evaluation by domain experts of the rates and cross sections for atomic and molecular processes that are needed for understanding and modeling the atmospheres in the solar system. We envision data products resembling those of the JPL/NASA Panel for Data Evaluation and the similar efforts of the international combustion modeling community funded by US DoE and its European counterpart

Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study.

As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism

The temporal changes in the emission spectrum of Comet 9P/Tempel 1 after Deep Impact

The time dependence of the changes in the emission spectra of Comet 9P/Tempel 1 after Deep Impact are derived and discussed. This was a unique event because for the first time it gave astronomers the opportunity to follow the time history of the formation and decay of O(1S), OH, CN, C2, C3, NH, and NH2. Least squares fits of a modified Haser model with constraints using known rate constants were fit to the observed data. In the case of OH a simple two-step Haser model provides a reasonable fit to the observations. Fitting the emissions from O(1S), CN, C2, C3, NH, and NH2 requires the addition of a delayed component to a regular two or three step Haser model. From this information a picture of the Deep Impact encounter emerges where there is an initial formation of gas and dust, which is responsible for the prompt emission that occurs right after impact. A secondary source of gas starts later after impact when the initial dust has dissipated enough so that solar radiation can reach the surface of freshly exposed material. The implications of this and other results are discussed in terms of the implications on the structure and composition of the comet's nucleus.Comment: Accepted for publication in The Astrophysical Journal; 26 pages including 8 figures and 1 tabl

Wireless event-recording device with identification codes

A wireless recording device can be interrogated to determine its identity and its state. The state indicates whether a particular physical or chemical event has taken place. In effect, the physical or chemical event is recorded by the device. The identity of the device allows it to be distinguished from a number of similar devices. Thus the sensor device may be used in an array of devices that can be probed by a wireless interrogation unit. The device tells the interrogator who it is and what state it is in. The interrogator can thus easily identify particular items in an array that have reached a particular condition

Caffeine Versus Methylphenidate and d-Amphetamine in Minimal Brain Dysfunction: A Double-Blind Comparison

The authors compared the efficacy of caffeine, methylphenidate, and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design. The slight improvement with caffeine was not significantly better than placebo. Both prescription drugs resulted in significant improvement and were significantly superior to caffeine. The authors suggest that the discrepancy between these results and an earlier, more optimistic report may stem from the use in this study of pure caffeine rather than whole coffee