BACKGROUND: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). METHODS: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report. RESULTS: The plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P < 0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92−7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83−34.44). Results were similar when we compared plasma S1P levels at the 1-year visit. CONCLUSIONS: The associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.
Animals ; Bone Density ; Cohort Studies ; Ecthyma, Contagious ; Female ; Humans ; Open Reading Frames ; Osteoporosis* ; Osteoporotic Fractures* ; Outcome Assessment (Health Care) ; Plasma* ; Prospective Studies ; Risk Assessment ; Risk Factors ; Sphingosine*

Objective: To investigate the neuroprotective efficacy of pomegranate and ellagic acid on the histopathological changes in the hippocampus of an aluminium chloride (AlCl3) induced rat model of Alzheimer's disease. Methods: Sprague Dawley rats were divided into 4 groups (n=10 each): Group I : serving as negative control; Group II, Alzheimer model, induced by administration of 17 mg/kg bw AlCl3; Group III, administered the same dose of AlCl3 with 50 mg/kg of pomegranate peel extract and Group IV : administered ellagic acid (50 mg/kg) in addition to the same dose of AlCl3. The medication given to all groups continued for 28 days. All were given the compounds by gastric gavage. Radial arm maze test, hippocampus antioxidant markers, histopathology of the dentate gyrus, and CA3 of the hippocampus were evaluated. Results: Rats treated with pomegranate peel extract exposed to radial arm maze test showed less number of errors and reduced time needed to reach the criterion. There was an increase in the levels of glutathione, catalase, and total antioxidant capacity and decreased lipid peroxidation products. Histopathological features in dentate gyrus and CA3 as apoptosis and chromatolysis of pyramidal cells and granular layer, respectively, were decreased. Alzheimer characteristic neurofibrillary tangles and senile plaques were reduced. Treatment with ellagic acid ameliorated the pathological results but to a statistically lower level. Conclusions: Pomegranate peel extract alleviates memory deficit and restores antioxidant homeostasis following degenerative changes in the hippocampus induced by aluminium chloride in rats..