6-methoxytryptophol reduces lipopolysaccharide-induced lipid peroxidation in vitro more effectively than melatonin.

Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in tissue homogenates in vitro in a concentration-dependent manner, the concentration of 400 µg/ml demonstrating the most efficient lipid damaging effect. Antioxidant properties of melatonin are unquestionable and have been proved both in vivo and in vitro. It has been demonstrated that also melatonin metabolites and derivatives inhibit oxidative stress. The aim of our study was to compare the effects of melatonin (MEL) and indole compound: 6-methoxytryptophol, on LPS-induced LPO in vitro. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indicators of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and 6-methoxytryptophol were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration of 400 µg/ml. In all the examined tissues, LPS stimulated LPO, while both melatonin and 6-methoxytryptophol released LPS-stimulated LPO. Furthermore, the capacity of 6-methoxytryptophol reducing LPO was higher than that of melatonin. The results of the reported study clearly indicate that 6-methoxytryptophol is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances.

Ten-year probability of osteoporotic fracture in 2012 Polish women assessed by FRAX and nomogram by Nguyen et al.-Conformity between methods and their clinical utility.

PURPOSE: The aim of the cross-sectional study was to establish the degree of conformity between 10-year probability of osteoporotic fracture, assessed by FRAX, and using the nomograms, as proposed by Nguyen at al. METHODS: Postmenopausal Polish women (2012) were examined in their mean age of 68.5+/-7.9 years (age range 55-90 years). Fracture probability by FRAX was based on age, BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis, alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture probability by Nguyen's nomograms was based on age, the number of prior fractures, the number of falls and T-score for femoral neck BMD. RESULTS: The mean conformity rate was 79.1% for any fracture risk (for threshold 20%) and 79.5% for hip fracture (threshold 3%). Any and hip fracture risks were significantly higher for both methods in women with fracture history in comparison to those without fracture and increased with ageing. The influence of prior fracture and ageing was more evident in Nguyen's nomograms. ROC analyses of any fracture risk in FRAX and Nguyen's methods demonstrated the area under curve (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture demonstrated AUCs for FRAX and Nguyen's technique at 0.726 and 0.850, respectively. The AUCs for Nguyen's nomograms were significantly larger than the AUCs for FRAX (p<0.0001). CONCLUSION: The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment, especially for hip fractures, due to a higher accuracy of the method. The information on the number of falls during the last year and multiple fractures ought to be incorporated into the method of fracture risk prediction. MINI-ABSTRACT: The degree of conformity was assessed in a group of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.'s nomograms. The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment due to higher accuracy.