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Xylazine (XYL), an FDA-approved veterinary tranquilizer, is being abused both as an opioid adulterant in a street-drug known as “Tranq-dope” and as a date rape drug. Given its now nearly ubiquitous use with fentanyl and fentanyl derivatives across the globe, XYL has become a primary target for researchers seeking to develop portable and cost-effective sensors for its detection. Electrochemical sensors based on the oxidation of XYL, while useful, have limitations due to certain interferents and inherent electrode fouling that render the approach less reliable, especially in certain sample matrices. In this work, modified electrode platforms incorporating layers of multi-walled carbon nanotubes for sensitivity along with semi-permeable polyurethane (PU) layers and host–guest chemistry using β-cyclodextrin for selectivity are deployed for XYL detection using complementary adsorptive cathodic stripping analysis. The modified electrode sensors are optimized to minimize high potentials and maintain fouling resistant capabilities and investigated to better understand the function of the PU layer. The use of adsorptive cathodic stripping differential pulse voltammetry indirectly indicates the presence and concentration of XYL within complex sample media (beverages and synthetic urine). When used in this manner, the modified electrodes exhibited an overall average sensitivity of ~35 (±9) nA/μM toward XYL with a limit of quantification of <10 ppm, while also offering adaptability for the analysis of XYL in different types of samples. By expanding the capability of these XYL sensors, this study represents another facet of tool development for use by medical professionals, first-responders, forensic investigators, and drug-users to limit exposure and help stem the dangerous and illegal use of XYL.

To the Editor: As Gupta et al. make clear in their Perspective article (June 15 issue), 1 illicit opioids are increasingly being adulterated with xylazine. Although we agree that it is important to be aware of xylazine, we disagree regarding the potential dangers associated with acute overdose. Gupta et al. state that xylazine intoxication may result in central nervous system depression, hypotension, and bradycardia. Although that’s mechanistically true, the doses required to produce sedation in animals (0.5 to 1.0 mg per kilogram of body weight) are typically much greater than those present in adulterated opioids. Thus, it is not clear that . . .

Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies.

Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.

Xylazine, increasingly implicated in illicit opioid overdose deaths, poses a significant public health threat due to its synergistic effects with fentanyl and resistance to naloxone reversal. Despite its rising prevalence, xylazine is not classified as a controlled substance, leading to its exclusion from routine forensic screening. This study introduces a novel analytical method combining Raman hyperspectral imaging with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to detect xylazine in drug mixtures containing common excipients such as acetaminophen, dipyrone, and mannitol. Utilizing only non-negativity constraints, MCR-ALS successfully resolved the Raman spectrum of xylazine at levels as low as 5 % without reference spectra. The method demonstrated robust performance, with percent variance explained (R²) values of 99.60 %, 99.80 %, and 99.91 % for the drug mixtures containing 25 %, 10 %, and 5 % xylazine, respectively. •First study using Raman hyperspectral imaging and MCR-ALS for xylazine detection.•Non-destructive, preparation-free method for screening powdery drug mixtures.•Detects xylazine at 5 % in mixtures with acetaminophen, dipyrone, and mannitol.•Achieves R2 > 99 % for xylazine detection with only non-negativity constraints.

Tissue oxygenation is well understood to impact radiosensitivity, with reports demonstrating a significant effect of breathing condition and anesthesia type on tissue oxygenation levels and radiobiological response. However, the temporal kinetics of intracellular and extracellular oxygenation have never been quantified, on the timescale that may affect radiotherapy studies. C57BL/6 mice were anesthetized using isoflurane at various percentages or ketamine/xylazine (ket/xyl: 100/10 mg/kg) ( N  = 48). Skin pO 2 was measured using Oxyphor PdG4 and tracked after anesthetization began. Oxyphor data was validated with relative measurements of intracellular oxygen via protoporphyrin IX (PpIX) delayed fluorescence (DF) imaging. Ex vivo localization of both PdG4 Oxyphor and PpIX were quantified. Under all isoflurane anesthesia conditions, leg skin pO 2 levels significantly increased from 12 to 15 mmHg at the start of anesthesia induction (4–6 min) to 24–27 mmHg after 10 min ( p  < 0.05). Ketamine/xylazine anesthesia led to skin pO 2 maintained at 15–16 mmHg throughout the 10-minute study period ( p  < 0.01). An increase of pO 2 in mice breathing isoflurane was demonstrated with Oxyphor and PpIX DF, indicating similar intracellular and extracellular oxygenation. These findings demonstrate the importance of routine anesthesia administration, where consistency in the timing between induction and irradiation may be crucial to minimizing variability in radiation response.

The current study was prepared to compare the efficacy of xylazine-lidocaine HCl and detomidine-lidocaine HCl following caudal epidural injection in horses, evaluating sedation, analgesia, physiological parameters, and hemato-biochemical values. This study was applied to six healthy adult horses (300–350 kg, > 4 years of age). The horses were randomly divided into two equal groups. Group 1 (seven horses) received xylazine (0.17 mg/kg bwt) + lidocaine HCl (0.06 mg/kg bwt), while Group 2 received detomidine (0.03 mg/kg bwt) + lidocaine HCl (0.06 mg/kg bwt) via caudal epidural injection. Perineal analgesia and sedation (onset time and duration) were assessed before administration and at 15, 30, 60, 90, and 120 min post-administration. Concurrently, heart rate, respiratory rate, rectal temperature, and hemato-biochemical values were recorded. The sedative duration of detomidine was longer than that of xylazine (94 ± 0.96 vs. 85 ± 0.94 min). Both detomidine and xylazine induced complete bilateral perineal analgesia in all horses. Analgesia onset was slightly faster and duration longer in detomidine-treated horses compared to xylazine, and these values are for onset of analgesia (11.79 ± 1.15 vs. 14.46 ± 0.92 min). Significant heart rate depression was observed in Group 2, in which both white blood cell count (WBC) and packed cell volume (PCV) percentage showed significant decreases. Conclusion and Clinical Relevance : The findings of this study suggest that epidural administration of detomidine-lidocaine HCl results in more effective and longer-lasting perineal analgesia compared to xylazine-lidocaine HCl.