Human red blood cell acetylcholinesterase activity: a revisit after fifteen years.

Human red blood cell acetylcholinesterase (RBC-AChE) activity is valuable for detecting potential exposure to cholinesterase inhibiting substances (CIS). A reliable population-based RBC-AChE activity reference range is critical for early and massive clinical and occupational toxicology screening. Previous published studies were often limited to small numbers of subjects, various testing methods, and crude statistical data analyses. We tested 4818 adult subjects with a well-established 17-minute modified Michel method over a 2-year period. We conducted a retrospective data analysis and systematically investigated on the influences to testing values from gender, age, age group, and their combinations and interactions. No significant difference was observed in the testing values between males (mean, medium, interquartile range = 0.76, 0.76, 0.71-0.80 ΔpH/h, respectively) and females (mean, medium, interquartile range = 0.76, 0.76, 0.71-0.81 ΔpH/hour, respectively), when gender was the only factor considered (p = 0.7238). However, with age progression, male testing values exhibited a consistent upward trend, while females did not show any clear patterns. Linear regression analysis of the data revealed that gender, age, and age group more or less affected testing values either as independent variables or with their combinations and interactions. However, more potential factors need to be included to achieve better testing value predictions. We recommend the toxicological testing community to adopt a new set of age group specific RBC-AChE activity reference ranges for males (0.68-0.80, 0.69-0.81, 0.70-0.83, 0.71-0.84, and 0.73-0.87 ΔpH/h for 18-29, 30-39, 40-49, 50-59, and ≥60 years old, respectively) while keeping the current reference range (0.63-0.89 ΔpH/hour) for females.

Evaluation of a Highly Efficient Multidrug Biochip Array Technology for a Simultaneous and High-Throughput Urine Drug Screening in Clinical and Toxicological Settings.

BACKGROUND: A high-throughput and highly efficient analytical platform for urine drug screening is critical in both clinical and forensic settings. Mass spectrometry (MS) has better sensitivity and specificity than conventional immunoassays (IA); however, not all laboratories have the necessary resources and workforce to operate MS. The goal of this study was to evaluate a multidrug biochip with 20 discrete testing regions (DTRs) for high-throughput urine drug screening (UDS). METHODS: The Randox DOA Ultra Urine (DOAULT URN) biochip employs chemiluminescent IA to detect various analytes, including stimulants, hallucinogens, sedatives, narcotics, and dextromethorphan. The verification included the evaluation of the limits of detection (LOD), stability of calibrators and controls, cross-reactivity, carryover, interference, and overall performance. RESULTS: LODs < quality control low for each DTR. The reconstituted calibrators were stable for up to 2 weeks at -20°C. Controls were stable for 4-6 hours at 22-25°C, with <20% within-day and ≤23% between-day imprecision. The accuracy of the controls (%bias) was within ±20% of the target concentration, except for dextromethorphan at -23.8%. No interference was observed with common over-the-counter medications. No carryover was detected in the high-concentration samples. Satisfactory cross-reactivity (≥50%) with known analytes produced presumptive positive results, with readings higher than the proposed decision points. The overall biochip performance of 165 confirmed samples showed 98.0% sensitivity, 96.9% specificity, and 97.5% efficiency. CONCLUSIONS: The DOAULT URN biochip is a multidrug analyte IA capable of detecting dozens of parent drugs and their metabolites in urine. It offers clinical and forensic laboratories an alternative UDS tool with LODs comparable to those of MS.

A Hidden Gem: Highlighting the Indispensable Capabilities and History of the DoD Cholinesterase Monitoring Program and DoD Cholinesterase Reference Laboratory.

The DoD Cholinesterase Monitoring Program and Cholinesterase Reference Laboratory have safeguarded U.S. government employees in chemical defense for over five decades. Considering Russia's potential deployment of chemical warfare nerve agents in Ukraine, it is critical to maintain a robust cholinesterase testing program and its efficiency presently and in future.

Impact of cannabis-infused edibles on public safety and regulation.

Popularity of cannabis-infused products has bloomed since legalization for recreational use of marijuana started. Consumption of cannabis edibles has steadily increased, as restrictions on recreational cannabis smoking have become tighter. This phenomenon enhanced the possibility of these products crossing the state line. The most psychoactive component of cannabis, ∆9-tetrahydrocannabinol (THC) is infused in "edibles" and linked to physiological and psychological effects. Consumers unfamiliar with these edibles may mistake them for non-THC containing products, causing unintended use or overconsumption. In addition, these cannabis-infused edibles are posing significant health risks. The FDA has recognized the potential dangers and recommended that cannabis remain as a Schedule I substance and illegal at the federal level. However, states maintain control of determining the legality of cannabis related products, and creating guidelines distinguishing cannabis edibles from the non-cannabis containing products. Recently, the State of Maine offers a blueprint for edible regulation that should be implemented in all states that are considering or have legalized marijuana.

Design, synthesis, and antiviral evaluation of some 3'-carboxymethyl-3'-deoxyadenosine derivatives.

3'-Carboxymethyl-3'-deoxyadenosine derivatives were prepared from 2'-O-TBDMS-3'-[(ethoxycarbonyl)methyl]-3'-deoxyadenosine (1) via simple and efficient procedures. Conversion of 1 to its 5'-azido-5'-deoxy derivative 5 was accomplished via a novel one-pot method employing 5'-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 5 was converted to 5'-[(N-methylcarbamoyl)amino] derivative 8 via one-pot reduction/acylation employing H(2)/Pd-C followed by treatment with p-nitrophenyl N-methylcarbamate. N(6)-phenylcarbamoyl groups were introduced by treatment with phenylisocyanate, and an efficient new method for lactonization of 2'-O-TBDMS-3'-[(ethoxycarbonyl)methyl]-3'-deoxyadenosines to give corresponding 2',3'-lactones was also developed. Target compounds were evaluated for anti-HIV and anti-HIV integrase activities, but were not active at the concentrations tested.

Stereocontrol in asymmetric S(E)' reactions of γ-substituted α,ß-unsaturated aldehydes.

Asymmetric SE' reactions of (E)- and (Z)-γ-substituted-α,ß-unsaturated aldehydes have been studied for the stereocontrolled preparation of nonracemic alcohols. Mild exchange reactions of allylic stannanes provide access to chiral 1,3-bis(tolylsulfonyl)-4,5-diphenyl-1,3-diaza-2-borolidines. These reagents display reactivity with the γ-substituted α,ß-unsaturated aldehydes, which is characterized by matched and mismatched elements of stereocontrol. Computational analysis (using density functional theory) provides valuable insights to guide reaction development.