A two-step synthetic strategy to obtain a water-soluble derivative of curcumin with improved antioxidant capacity and in vitro cytotoxicity in C6 glioma cells.

A novel water-soluble derivative of curcumin (Cur-[G-2]-OH) was designed and synthesized from accessible raw materials in only two steps with an overall yield of 80%. The modification of curcumin phenol groups with second-generation polyester dendrons (dendronization) as a strategy to achieve an optimal hydrophilic/hydrophobic balance allows the complete water solubilization of the new curcumin derivative (5mg/ml) at room temperature. The therapeutic potential of Cur-[G-2]-OH was investigated in terms of antioxidant capacity, intracellular uptake and cytotoxicity in both rat glioblastoma cells and normal human dermal fibroblasts. Although the phenolic groups of curcumin were locked by dendronization, Cur-[G-2]-OH exhibited antioxidant capacity in water that was even higher than curcumin in dimethylsulfoxide (DMSO). This compound showed a steady cellular uptake contrasted with curcumin, which has a saturation capture at high concentrations. Combined with improved stability, this property seems to allow the intracellular accumulation of Cur-[G-2]-OH. Furthermore, the new compound exhibited increased cytotoxicity in rat C6 glioma cells in a time- and concentration-dependent manner, whereas in normal human fibroblasts, its IC50 value was >600µM versus the IC50 of curcumin found between 100 and 200µM. Surprisingly, Cur-[G-2]-OH drives cell death of C6 cells by a different mechanism of apoptosis triggered by curcumin. Together, these results suggest that curcumin dendronization could promote molecular and cellular mechanisms that are different from those induced by curcumin, presumably due to structural factors and not only for improved water solubility.

Ability of ICU Health-Care Professionals to Identify Patient-Ventilator Asynchrony Using Waveform Analysis.

BACKGROUND: Waveform analysis by visual inspection can be a reliable, noninvasive, and useful tool for detecting patient-ventilator asynchrony. However, it is a skill that requires a properly trained professional. METHODS: This observational study was conducted in 17 urban ICUs. Health-care professionals (HCPs) working in these ICUs were asked to recognize different types of asynchrony shown in 3 evaluation videos. The health-care professionals were categorized according to years of experience, prior training in mechanical ventilation, profession, and number of asynchronies identified correctly. RESULTS: A total of 366 HCPs were evaluated. Statistically significant differences were found when HCPs with and without prior training in mechanical ventilation (trained vs non-trained HCPs) were compared according to the number of asynchronies detected correctly (of the HCPs who identified 3 asynchronies, 63 [81%] trained vs 15 [19%] non-trained, P < .001; 2 asynchronies, 72 [65%] trained vs 39 [35%] non-trained, P = .034; 1 asynchrony, 55 [47%] trained vs 61 [53%] non-trained, P = .02; 0 asynchronies, 17 [28%] trained vs 44 [72%] non-trained, P < .001). HCPs who had prior training in mechanical ventilation also increased, nearly 4-fold, their odds of identifying ≥2 asynchronies correctly (odds ratio 3.67, 95% CI 1.93-6.96, P < .001). However, neither years of experience nor profession were associated with the ability of HCPs to identify asynchrony. CONCLUSIONS: HCPs who have specific training in mechanical ventilation increase their ability to identify asynchrony using waveform analysis. Neither experience nor profession proved to be a relevant factor to identify asynchrony correctly using waveform analysis.