Early detection of liver injuries by the Serum enhanced binding test sensitive to albumin post-transcriptional modifications.

Early and sensitive biomarkers of liver dysfunction and drug-induced liver injury (DILI) are still needed, both for patient care and drug development. We developed the Serum Enhanced Binding (SEB) test to reveal post-transcriptional modifications (PTMs) of human serum albumin resulting from hepatocyte dysfunctions and further evaluated its performance in an animal model. The SEB test consists in spiking serum ex-vivo with ligands having specific binding sites related to the most relevant albumin PTMs and measuring their unbound fraction. To explore the hypothesis that albumin PTMs occur early during liver injury and can also be detected by the SEB test, we induced hepatotoxicity in male albino Wistar rats by administering high daily doses of ethanol and CCl4 over several days. Blood was collected for characterization and quantification of albumin isoforms by high-resolution mass spectrometry, for classical biochemical analyses as well as to apply the SEB test. In the exposed rats, the appearance of albumin isoforms paralleled the positivity of the SEB test ligands and histological injuries. These were observed as early as D3 in the Ethanol and CCl4 groups, whereas the classical liver tests (ALT, AST, PAL) significantly increased only at D7. The behavior of several ligands was supported by structural and molecular simulation analysis. The SEB test and albumin isoforms revealed hepatocyte damage early, before the current biochemical biomarkers. The SEB test should be easier to implement in the clinics than albumin isoform profiling.

Minors and young adult's hospitalizations after "chimique" consumption in Mayotte Island: Which substances are involved?

OBJECTIVES: Over the last 10 years, the use of an unknown drug called "chimique" has emerged, among adolescents and young adults in precarious situations in Mayotte Island. To date, the exact composition of "chimique" is still poorly documented, but seizures made on the Island at the same time indicated that it would be mainly composed of synthetic cannabinoids receptor agonists (SCRAs). The objective of this study was to identify which substances, among those consumed under the name of "chimique", leading to hospital admissions. METHODS: Between 1st march and 30th June 2019, all patients, over 14 years old, hospitalized in the emergency department of Mayotte hospital after use of "chimique" for which the physician required toxicological analysis were included. Blood samples and clinical data were recorded for each patient. Toxicological analyses were performed using high resolution mass spectrometry (UPLC-MS/QTOF). RESULTS: Twelve patients were included: 11 males and 1 female. The mean age was 26 years (median age: 22). There were 2 minors. Clinical presentations varied, mainly psychiatric and neurologic disorders were observed. No death was reported. Toxicological analysis identified psychoactive substances such as THC and/or its metabolites (n=3) and MDMB-4en-PINCA (n=2). The other substances identified were mainly part of the patients' treatment. CONCLUSION: This is the first study conducted in the Indian Ocean confirming the presence of SCRAs in the "chimique". For a while, the consumption of SCRAs in France seemed to be of limited importance. However, their use has become important in the Indian Ocean since the spread of "chimique" in Mayotte. It continues to spread especially in Reunion Island since 2017 under the name of "chamane".

How Long Do Implanted Triclosan Sutures Inhibit Staphylococcus aureus in Surgical Conditions? A Pharmacological Model.

(1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan antistaphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poliglecaprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h.

Involuntary MDMB-4en-PINACA intoxications following cannabis consumption: clinical and analytical findings.

BACKGROUND AND AIMS: MDMB-4en-PINACA is a synthetic cannabinoid receptor agonist (SCRA) that has recently emerged. Data regarding clinical presentations in the event of intoxication is scarce. This study presents MDMB-4en-PINACA identification in cannabis consumers with clinical and analytical descriptions. METHODS: Between November 2020 and March 2021, all patients with unexpected or unusually severe effects and Poisoning Severity Score (PSS) greater than or equal to 2 after cannabis consumption were included. Blood and/or urine samples were collected for toxicological analysis. When available, drug material samples were also collected for analysis. RESULTS: Between November 2020 and March 2021, 13 patients were included. All cases typically presented with altered mental status (n = 13), and nearly all had returned to a normal or quasi-normal state after around 11 h of observation. Neurological symptoms included headaches (n = 3), hallucinations (3), mydriasis (3), amnesia (2) and seizures (5). Psychiatric symptoms were paranoia (6) and anxiety (2). Digestive symptoms were nausea (2) and vomiting (6). No deaths were recorded. All patients were positive for the SCRA MDMB-4en-PINACA in urine, blood and/or drug material sample. Results from toxicology testing paired with case history showed the potential for MDMB-4en-PINACA to cause or contribute to different clinical disorders. CONCLUSIONS: This study highlights the risk of intoxication by SCRAs when taking low-THC cannabis products. Forensic scientists, public health and public safety officials, law enforcement personnel and clinicians should be aware of the impact that these emergent SCRAs may have in their work, especially MDMB-4en-PINACA.

Hair Analysis of Methoxphenidine in a Forensic Chemsex Case.

Methoxphenidine (MXP, 2-MeO-diphenidine) is a dissociative anesthetic drug of the diarylethylamine type, recently introduced for recreational purposes through the online-based sale of new psychoactive substances (NPSs). The concentration of MXP in hair has never been reported, either in cases of chemsex use or in fatal cases. A 55-year-old man was found dead at his home the morning after a chemsex party. Toxicological analyses indicated high concentrations of MXP in femoral blood (606 µg/L), cardiac blood (254 µg/L) and hair (13 ng/mg). We also identified 3-methylmethcathinone (3-MMC) in femoral blood (traces) and urine (238 µg/L). The concentrations of all other drugs were consistent with living subjects. This case highlights the risk of MXP poisoning in the context of chemsex and emphasizes the importance of including NPS in postmortem toxicology examinations.