Cytotoxic Effects of 3,4-Catechol-PV (One Major MDPV Metabolite) on Human Dopaminergic SH-SY5Y Cells.

3,4-Methylenedioxypyrovalerone (MDPV), one of the most commonly abused synthetic cathinones, has caused several intoxications and deaths despite its short presence on the market. Apart from its effects on the monoamine systems in the brain, recent in vitro investigations have revealed cytotoxicity. In this study, the effects of increasing concentrations (10-1000 µM) of 3,4-Catechol-PV, one of major MDPV metabolites, on cell viability, morphology, and apoptosis have been evaluated after acute exposure (24-48 h) in human neuroblastoma SH-SY5Y cells-undifferentiated and differentiated to a more mature neuronal-like phenotype. Results indicated the following: (i) Cell viability: concentration-dependent decrease (15-55%) in differentiated SH-SY5Y after 24 h, with no exacerbation after 48 h (LC50 values 1028 and 951 µM, respectively); marked concentration-dependent decrease after 48 h (20-63%) in undifferentiated SH-SY5Y (LC50 553.9 µM) with mild effect (18-22% cell death) after 24 h at ≥ 500 µM only; the lowest toxic concentrations were 500 and 100 µM after 24 h, for undifferentiated and differentiated SH-SY5Y, respectively, and 10 µM after 48 h. (ii) Concentration- and time-dependent alterations of cell morphology in both SH-SY5Y types characterized by several intracellular cytoplasmic vesicles (undifferentiated more susceptible (effect at ≥ 50 µM) than differentiated cells (effect at ≥ 100 µM)), loss of the typical cell shape, neurite retraction, and cell density decrease. (iii) Activation of caspase-3 enzyme in differentiated and undifferentiated cells after 48 h. These findings suggest the potential involvement of 3,4-Catechol-PV in MDPV-induced neurotoxicity and support the use of this human cellular model as a species-specific in vitro tool to clarify the neurotoxicity mechanisms of synthetic cathinones and metabolites.

N-Acetyl-Cysteine as Effective and Safe Chelating Agent in Metal-on-Metal Hip-Implanted Patients: Two Cases.

Systemic toxicity associated with cobalt (Co) and chromium (Cr) containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014). After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL) are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable.

Infliximab-related hepatitis: discussion of a case and review of the literature.

Despite its rarity, infliximab-related hepatitis constitutes a cutting edge and challenging problem. In December 2004, a drug warning was issued by the Food and Drug Administration to alert healthcare professionals to the risk of hepatotoxicity in course of infliximab therapy. Subsequently, several reports of probable infliximab hepatitis have been published and interest is growing in trying to elucidate the impact of these events on clinical practice. After discussing our case report, the main characteristics of infliximab-mediated liver injury are analyzed, coupled with a review of the medical literature. Infliximab seems to provoke both immunomediated and a direct liver injury, but how this latter happens remains unclear. Moreover, infliximab immunomediated liver dysfunction resembles that of autoimmune hepatitis type I, with elevation of antinuclear, anti-smooth muscle, anti-double-strand DNA antibodies, and a clear preference for female sex. Finally, a flow chart is proposed with the purpose to help clinicians in the management of patients who develop signs of liver dysfunction during treatment with infliximab.