Naturally Derived Phenethyl Isothiocyanate Modulates Induction of Oxidative Stress via Its N-Acetylated Cysteine Conjugated form in Malignant Melanoma.

Phenethyl isothiocyanate (PEITC) is a secondary metabolic product yielded upon the hydrolysis of gluconasturtiin and it is highly accumulated in the flowers of watercress. The aim of the current study was to assess the role of a naturally derived PEITC-enriched extract in the induction of oxidative stress and to evaluate its anti-melanoma potency through the regulation of its metabolism with the concurrent production of the N-acetyl cysteine conjugated by-product. For this purpose, an in vitro melanoma model was utilized consisting of human primary (A375) cells as well as metastatic (COLO-679) malignant melanoma cells together with non-tumorigenic immortalized keratinocytes (HaCaT). Cytotoxicity was assessed via the Alamar Blue assay whereas the antioxidant/prooxidant activity of PEITC was determined via spectrophotometric assays. Finally, kinetic characterization of the end-product of PEITC metabolism was monitored via UPLC coupled to a tandem mass spectrometry (MS/MS). Our results indicate that although PhEF showed very minor antioxidant activity in a cell-free system, in a cell-based system, it can modulate the activity of key enzyme(s) involved in cellular antioxidant defense mechanism(s). In addition, we have shown that PhEF induces lipid and protein oxidation in a concentration-dependent manner, while its cytotoxicity is not only dependent on PEITC itself but also on its N-acetylated cysteine conjugated form.

The effect of obesity and increasing age on operative time and length of stay in primary hip and knee arthroplasty.

We retrospectively reviewed 589 patients undergoing lower-limb arthroplasty, recording age, body mass index (BMI) and co-morbidities. The effect of these on operative duration and length of stay (LOS) was analysed. For a 1 point increase in BMI we expect LOS to increase by a factor of 2.9% and mean theatre time to increase by 1.46minutes. For a 1-year increase in age, we expect LOS to increase by a factor of 1.2%. We have calculated the extra financial costs associated. The current reimbursement system underestimates the financial impact of BMI and age. The results have been used to produce a chart that allows prediction of LOS following lower limb arthroplasty based on BMI and age. These data are of use in planning operating lists.