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The article presents a study which validates the use of trimethyloxonium tetrafluoroborate (TMO) for in situ derivitization of Δ9-tetrahydrocannabinol (THC) and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) in human urine. The study used gas chromatography-mass spectrometry to detect the derivatives on selected ion monitoring mode. The results from the 60 real samples showed that the method was useful and reliable in THC-COOH routine analysis of human urine samples for forensic use.

Background and purpose.The aim of this study was to investigate, in vascular smooth muscle cells, the mechanical and electrophysiological effects of (+/−)-naringenin.Experimental approach.Aorta ring preparations and single tail artery myocytes were employed for functional and patch-clamp experiments, respectively.Key results.(+/−)-Naringenin induced concentration-dependent relaxation in endothelium-denuded rat aortic rings pre-contracted with either 20 mM KCl or noradrenaline (pIC50 values of 4.74 and 4.68, respectively). Tetraethylammonium, iberiotoxin, 4-aminopyridine and 60 mM KCl antagonised (+/−)-naringenin-induced vasorelaxation, while glibenclamide did not produce any significant antagonism. Naringin [(+/−)-naringenin 7-β-neohesperidoside] caused a concentration-dependent relaxation of rings pre-contracted with 20 mM KCl, although its potency and efficacy were significantly lower than those of (+/−)-naringenin. In rat tail artery myocytes, (+/−)-naringenin increased large conductance Ca2+-activated K+ (BKCa) currents in a concentration-dependent manner; this stimulation was iberiotoxin-sensitive and fully reversible upon drug wash-out. (+/−)-Naringenin accelerated the activation kinetics of BKCa current, shifted, by 22 mV, the voltage dependence of the activation curve to more negative potentials, and decreased the slope of activation. (+/−)-Naringenin-induced stimulation of BKCa current was insensitive either to changes in the intracellular Ca2+ concentration or to the presence, in the pipette solution, of the fast Ca2+ chelator BAPTA. However, such stimulation was diminished when the K+ gradient across the membrane was reduced.Conclusions and Implications.The vasorelaxant effect of the naturally-occurring flavonoid (+/−)-naringenin on endothelium-denuded vessels was due to the activation of BKCa channels in myocytes.British Journal of Pharmacology (2006) 149, 1013–1021. doi:10.1038/sj.bjp.0706951; published online 6 November 2006 [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCLs) are a rare and heterogeneous subset of skin-localized, non-Hodgkin lymphomas. Our aim was to evaluate the in vitro antitumor activity of the multi-kinase inhibitor linifanib, either alone or in combination with metronomic vinorelbine (mVNR) or etoposide (mETO), on CTCL cells. In vitro proliferation assay and Luminex analysis showed that long-term, daily exposure of linifanib significantly inhibited the proliferation of the human CTCL cell line HH, in a concentration-dependent manner (IC 50  = 48.4 ± 20.4 nM) and the phosphorylation of AKT/mTOR signaling pathway. The concomitant exposure of linifanib plus mVNR or mETO resulted in a strong synergism, with combination index values < 1. Linifanib significantly increased the VNR and ETO intracellular concentrations in HH cells, evaluated by UPLC-HRMS technology, and strongly reduced the ABCB1 and ABCG2 gene expression in HH. In conclusion, we reported a striking antitumor activity of daily, long-term linifanib and a clear synergistic effect when administered in combination with mCHEMO on CTCL cells, as a promising base for future clinical approaches in T-cell lymphomas., Competing Interests: Declarations. Consent for publication: All authors have read and agreed to the published version of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The term "planned complex suicide" refers to cases where two or more suicide methods are applied simultaneously. Plastic bag suffocation is a suicidal method commonly combined with self-poisoning by inhalation of volatile compounds or pharmacological substances at poisoning dosage. A 67-year-old woman was found dead on the couch. The head was wrapped in a plastic bag knotted at the front of the neck. No signs of struggle were present on the scene. In the fireplace, there were two blisters of acetaminophen/codeine phosphate tablets. Postmortem examination showed congestion of the face and the neck and pulmonary edema with patchy emphysema. There was no evidence of physical duress. Toxic levels of codeine were detected in the blood. The death was related to a complex suicide involving codeine overdose and asphyxia by plastic bag suffocation. The hypoxic/cardioinhibitory effects of plastic bag suffocation combined to codeine-induced deep reduction of respiratory rate, making the suicide hypothesis the more likely scenario. In order to assess what elements contribute to postmortem diagnosis in complex suicides with plastic bag suffocation, a review of the forensic literature published between 2002 and 2022 was performed. This article emphasizes the complexity of diagnosing deaths involving plastic bag suffocation in suicides, particularly when combined with other methods like inert gas inhalation or drug intake. It underscores the importance of comprehensive toxicological analyses, careful scene examination, and histological studies, not forgetting a thorough comparative analysis of the existing literature, to accurately determine the cause and manner of death in such cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In December 2020, the World Health Organization (WHO) declared SARS-CoV2 a global pandemic. Home confinement, low social contacts, and fear of virus transmission played a major role as risk factors for suicides during the following period. Suicide pacts, in particular, showed a different pattern. A rare case of a triple suicide pact among members of the same family nucleus is presented. The victims were an elderly, severely ill woman and her adult children (a son and daughter), linked by a morbid relationship. The last time the family was seen alive was 40 days before the discovery. All corpses presented decompositional changes. After a full autopsy, the cause of death was determined to be a lethal intake of morphine for the mother and acute blood loss due to self-stabbing at the neck for the siblings. The younger woman was under the effects of a large amount of heparin. Toxicological analysis was positive for opioids and alcohol in both siblings. Suicide pacts have rarely been described during the COVID-19 pandemic. In the few cases reported, the victims were more often relatives than people in a romantic relationship. The involvement of three people is unusual, as is the use of different suicide methods among the victims. In the presented case, the elderly mother's imminent death from terminal cancer, her concern over dying in a nondomestic environment, and the siblings' fear of being alone likely led to the conception of the suicide pact. Social isolation and economic difficulties also played a contributing role., (© 2023 American Academy of Forensic Sciences.)

Introduction: The dynamism in the regulatory frameworks concerning the consumption of cannabinoids has placed their effects on cognitive and psychomotor skills at the center of the scientific debate. In consideration of the potential repercussions on public safety, particular attention has been focused on the impairment of driving skills, opening up the need to specifically regulate driving under the effects of cannabinoids., Pharmacokinetics: Both native cannabinoids and metabolites show a long positivity at low concentrations in the biological fluids, especially in the case of chronic consumption. Qualitative positivity to cannabinoids does not itself prove the presence of detrimental effects, which require the presence of active substances at relevant concentrations. Driving Skill Impairment: Multiple studies highlight a tetrahydrocannabinol (THC) concentration- based alteration of driving skills mainly affecting automatisms, whereas skills subjected to cognitive control are preserved up to higher dosages. The evidence relating to associations with other substances, chronic consumption and other cannabinoids, on the other hand, is still burdened by a high degree of uncertainty. Regulation Policies: Different models can be adopted in the regulation of driving under the effects of cannabinoids: sanctions can be applied in case of qualitative positivity, cannabinoids concentration above a defined threshold, or in presence of a demonstrated state of cognitive alteration., Conclusion: "Per se limit" with a quantitative THC cut-off between 3.5 and 5 ng/ml can currently be considered the most balanced choice. Finally, the analysis carried out allowed to identify pitfalls in both scientific and legislative fields for the improvement of safety policies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To explore the possible etiology of multiple osteomata on a skull and long bones from an individual from a medieval site in Tuscany, Italy., Materials: Human skeletal remains dating to the 10 th -12 th century AD from the parish church of S. Pietro in Pava, in the province of Siena (Tuscany, Central Italy)., Methods: Macroscopic and imaging analyses (Cone Beam Computed Tomography)., Results: Nine round-shaped new bone formations are observed on a female individual aged 40-50 years. The lesions have a smooth surface and range from 2.2-6 mm in diameter., Conclusions: Cone Beam Computed Tomography confirmed that the lesions were composed of compact bone. Macroscopic and radiological features suggest the presence of nonsyndromic multiple osteomata., Significance: Single cranial osteomata are commonly observed in osteoarchaeological remains, but multiple osteomata are rare and might assist in our understanding of neoplastic conditions in the past., Limitations: The lack of soft tissues prevents the diagnosis of complex disorders, such as the Gardner syndrome, which is characterised by multiple osteomata and polyposis of the colon., Suggestions for Further Research: Careful investigation and reporting of all neoplastic lesions in ancient human remains in order to increase our knowledge about the etiology in past human populations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to explore the pharmacokinetics of the two main active compounds (THC and CBD) contained in the cannabis oil extract Bedrocan® in fasting and fed dogs. Bedrocan® (20% delta-9-tetrahydrocannabinol [THC] and 0.5% cannabidiol [CBD]) was administered at 1.5 and 0.037 mg/kg THC and CBD, respectively in fasted and fed dogs according to a 2 × 2 cross over study design. The quantification of the two active ingredients was performed by LC/MS. No detectable concentrations of CDB were found at any collection time. THC was quantifiable from 0.5 to 10 h, although there was large inter-subject variability. Fed dogs showed a longer absorption phase (Tmax 5 vs 1.25 h) and lower maximal blood concentration (7.1 vs 24 ng/mL) compared with the fasted group. A larger AUC was found in the fasted group; the relative oral bioavailability in fed animals was 48.22%., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A novel aqueous in situ derivatization procedure with propyl chloroformate (PCF) for the simultaneous, quantitative analysis of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxy-Δ 9 -tetrahydrocannabinol (OH-THC) and 11-nor-Δ 9 -tetrahydrocannabinol-carboxylic acid (THC-COOH) in human blood and urine is proposed. Unlike current methods based on the silylating agent [N,O-bis(trimethylsilyl)trifluoroacetamide] added in an anhydrous environment, this new proposed method allows the addition of the derivatizing agent (propyl chloroformate, PCF) directly to the deproteinized blood and recovery of the derivatives by liquid-liquid extraction. This novel method can be also used for hydrolyzed urine samples. It is faster than the traditional method involving a derivatization with trimethyloxonium tetrafluoroborate. The analytes are separated, detected and quantified by gas chromatography-mass spectrometry in selected ion monitoring mode (SIM). The method was validated in terms of selectivity, capacity of identification, limits of detection (LOD) and quantification (LOQ), carryover, linearity, intra-assay precision, inter-assay precision and accuracy. The LOD and LOQ in hydrolyzed urine were 0.5 and 1.3 ng/mL for THC and 1.2 and 2.6 ng/mL for THC-COOH, respectively. In blood, the LOD and LOQ were 0.2 and 0.5 ng/mL for THC, 0.2 and 0.6 ng/mL for OH-THC, and 0.9 and 2.4 ng/mL for THC-COOH, respectively. This method was applied to 35 urine samples and 50 blood samples resulting to be equivalent to the previously used ones with the advantage of a simpler method and faster sample processing time. We believe that this method will be a more convenient option for the routine analysis of cannabinoids in toxicological and forensic laboratories., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved., Methods: This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings., Key Findings: Pharmacological characterization led us to exclude the involvement of NO pathway (neither L-NAME, NO biosynthesis inhibitor, nor ODQ, guanylate cyclase inhibitor, was able to modify the vascular effects of carvacrol) and of arachidonic acid cascade (no inhibitor intercepting the cascade influenced the endothelial-dependent vasodilatation of the monoterpene). Moreover, endothelial TRP channels were also not involved, as capsazepine did not antagonize vasorelaxing effect. Finally, endothelial potassium channels were considered as possible targets of carvacrol; indeed, two voltage-operated potassium (Kv) channel blockers, 4-aminopyridine and quinine, significantly reduced carvacrol potency and efficacy indices., Conclusions: Kv channels seem to be responsible for vascular effects of the monoterpene typical of Labiatae family., (© 2016 Royal Pharmaceutical Society.)

A sensitive and reliable method for extraction and quantification of benzoylecgonine (BZE) and cocaine (COC) in urine is presented. Propyl-chloroformate was used as derivatizing agent, and it was directly added to the urine sample: the propyl derivative and COC were then recovered by liquid-liquid extraction procedure. Gas chromatography-mass spectrometry was used to detect the analytes in selected ion monitoring mode. The method proved to be precise for BZE and COC both in term of intraday and interday analysis, with a coefficient of variation (CV)<6%. Limits of detection (LOD) were 2.7 ng/mL for BZE and 1.4 ng/mL for COC. The calibration curve showed a linear relationship for BZE and COC (r2>0.999 and >0.997, respectively) within the range investigated. The method, applied to thirty authentic samples, showed to be very simple, fast, and reliable, so it can be easily applied in routine analysis for the quantification of BZE and COC in urine samples., (© 2015 American Academy of Forensic Sciences.)