Heterotetrameric N-methyl-d-aspartate type glutamate receptors (NMDAR) are cationic channels primarily permeable for Ca2+. NR1 and NR3 subunits bind glycine, while NR2 subunits bind glutamate for full activation. As NR1 may contain a nuclear localization signal (NLS) that is recognized by importin-α, our aim was to investigate if NMDARs are expressed in the nuclei of melanocytes and melanoma cells. A detailed NMDAR subunit expression pattern was examined by RT-PCRs (reverse transcription followed by polymerase chain reaction), fractionated western blots and immunocytochemistry in human epidermal melanocytes and in human melanoma cell lines A2058, HT199, HT168M1, MEL35/0 and WM35. All kind of NMDAR subunits are expressed as mRNAs in melanocytes, as well as in melanoma cells, while NR2B protein remained undetectable in any cell type. Western blots proved the exclusive presence of NR1 and NR3B in nuclear fractions and immunocytochemistry confirmed NR1-NR3B colocalization inside the nuclei of all melanoma cells. The same phenomenon was not observed in melanocytes. Moreover, protein database analysis revealed a putative NLS in NR3B subunit. Our results support that unusual, NR1-NR3B composed NMDAR complexes are present in the nuclei of melanoma cells. This may indicate a new malignancy-related histopathological feature of melanoma cells and raises the possibility of a glycine-driven, NMDA-related nuclear Ca2+-signalling in these cells.
Baclofen intoxication, once rare, is now increasingly observed in clinical and forensic settings due to its expanding medical and off-label use. However, baclofen is not routinely included in standard postmortem toxicological panels and is usually tested only when explicitly requested. This selective approach, together with the lack of validated cut-offs and standardized interpretative protocols, complicates both clinical management and postmortem evaluation. A systematic review of the literature published between July 2005 and July 2025 was conducted according to PRISMA guidelines, including fatal and non-fatal baclofen intoxications with quantitative toxicological data. Analytical methods, biological matrices, concentration ranges, and clinical outcomes were compared to identify recurring patterns and interpretative gaps. A fatal intrathecal overdose case was also analyzed as a paradigmatic example of diagnostic and methodological challenges. In thirteen studies meeting inclusion criteria and comprising over 300 cases, reported blood concentrations ranged from 0.04 to 110 mg/L, with overlapping values between survivors and fatalities. The analysis revealed marked heterogeneity in matrices and methods, and a poor correlation between concentration and clinical severity, limiting the reliability of toxicological interpretation in both clinical and postmortem settings. Baclofen intoxication illustrates the challenges of interpreting toxicological data without harmonized analytical criteria and highlights the need for standardized procedures and shared reference databases to improve diagnostic and medico-legal accuracy.
A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.