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Alprazolam is a psychoactive triazolo-benzodiazepine, commonly prescribed for the treatment of anxiety disorders and considered safe due to its high therapeutic index. It is frequently detected in polydrug-related deaths but there are very few cases of fatal intoxication by alprazolam not in combination with alcohol or other drugs. A fatal poisoning by alprazolam in a 60-years old male physician has been reported. At autopsy, no evidence of traumatic injuries or diseases was observed except for signs of bronchopneumonia and slight hypertrophy of the left ventricle. Alprazolam and its major metabolite (α-hydroxyalprazolam) were detected in biological samples through liquid chromatography-tandem mass spectrometry (LC-MS/MS). High concentrations of alprazolam and α-hydroxyalprazolam were found, respectively, in femoral blood 0.45 and 0.03 mg/L, urine 2.12 and 0.42 mg/L, bile 1.33 and 0.56 mg/L, liver 3.81 and 0.28 mg/L. Alprazolam alone was also detected in vitreous humour (0.19 mg/L) and in stomach content (0.34 mg/L). No conclusive information confirmed the hypothesis of a suicidal ingestion of alprazolam. However, an alprazolam drug-related death was assessed based on the pre-existing cardiovascular and respiratory defects. The high levels of alprazolam several times greater than the therapeutic range contributed to death due to its respiratory and central nervous system-depressant effects. [ABSTRACT FROM AUTHOR]

Aims: This study assessed the use of matrix‐assisted laser desorption/ionization time of flight (MALDI‐TOF) mass spectrometry as an alternative method to identify species associated with the thanatomicrobiota and epinecrotic communities. Methods and Results: The study was conducted on 10 murine cadavers, and microbiological swabs were collected from five external anatomical sites (eyes, ears, nose, mouth and rectum) and four internal organs (brain, spleen, liver, heart), during 16 and 30 days, for the thanatomicrobiota and epinecrotic communities, respectively. Our results revealed that the postmortem microbiota associated with the external cavities showed changes over time and reduced taxonomic diversity. The internal organs, initially sterile, showed signs of microbial invasion at 3 and 10 days postmortem for the liver‐spleen and heart‐brain, respectively. The postmortem microbiota was mainly dominated by Firmicutes and Proteobacteria. Conclusions: MALDI‐TOF is a promising method for estimating postmortem interval (PMI), associated with rapid sample handling, good reproducibility and high productivity. Significance and Impact of the Study: This study investigated microbial changes during the decomposition process and proposed a simple strategy for PMI estimation. Results introducing the application of the MALDI‐TOF method in the field of forensic. [ABSTRACT FROM AUTHOR]

Rationale: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. Objective: To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. Methods and results: We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. Conclusions: The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2. [ABSTRACT FROM AUTHOR]