Femoral Strength Changes Faster With Age Than BMD in Both Women and Men: A Biomechanical Study

Although a large number of studies have addressed the age‐related changes in bone mineral density (BMD), there is a paucity of data for the assessment of femoral strength loss with age in both genders. We determined the variation of strength with age in femurs of women and men by mechanical tests on a cohort of 100 cadaveric femurs. In addition, the age‐related neck BMD loss in our cadaveric cohort was found to be similar with BMD loss of four published population‐based studies. Given the strong correlation found in our cadaveric study between BMD and femoral strength, we also estimated the femoral strength of the four populations based on their reported neck BMDs. Our study showed that men's femurs in our cadaveric cohort were stronger than women's femurs by about 800 N at the same BMD level, and by 1750 N at the same age. The strength differences were not explained satisfactorily by the size difference between men's and women's bones. Similar to the findings of clinical studies, the BMD values of men at all ages were larger than that of women. The age‐related loss rates in BMD and strength were not statistically different between the two genders of our cadaveric cohort. After normalization, strength decreased more than 40% faster than BMD. On average, men reached a certain BMD value about 16 years later than women, and for strength about 23 years later, which may explain the higher rate of hip fracture in postmenopausal women. In patient population cohorts men reached a similar BMD value about 16 to 25 years later than women, whereas for estimated strength, sometimes more than 40 years later. © 2015 American Society for Bone and Mineral Research.     

Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants

Prion diseases are associated with the conversion of the alpha-helix rich prion protein (PrPC) into a beta-structure-rich insoluble conformer (PrPSc) that is thought to be infectious. The mechanism for the PrPC-->PrPSc conversion and its relationship with the pathological effects of prion diseases are poorly understood, partly because of our limited knowledge of the structure of PrPSc. In particular, the way in which mutations in the PRNP gene yield variants that confer different susceptibilities to disease needs to be clarified. We report here the 2.5-A-resolution crystal structures of three scrapie-susceptibility ovine PrP variants complexed with an antibody that binds to PrPC and to PrPSc; they identify two important features of the PrPC-->PrPSc conversion. First, the epitope of the antibody mainly consists of the last two turns of ovine PrP second alpha-helix. We show that this is a structural invariant in the PrPC-->PrPSc conversion; taken together with biochemical data, this leads to a model of the conformational change in which the two PrPC C-terminal alpha-helices are conserved in PrPSc, whereas secondary structure changes are located in the N-terminal alpha-helix. Second, comparison of the structures of scrapie-sensitivity variants defines local changes in distant parts of the protein that account for the observed differences of PrPC stability, resistant variants being destabilized compared with sensitive ones. Additive contributions of these sensitivity-modulating mutations to resistance suggest a possible causal relationship between scrapie resistance and lowered stability of the PrP protein.     

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study melanin free radicals in human retinal pigment epithelium (RPE) cells and tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in vivo light-induced melanin free radical photochemistry in more detail than previously known. Electron spin polarization reflecting a non-Boltzmann population within the energy levels of the spin system is observed in RPE cells as the result of the triplet state photoproduction and subsequent disappearance of free radicals in the melanin polymer. In a set of RPE cells cultured from individual sources, differences in optical absorption, continuous wave EPR spectra, and TREPR signals were correlated with apoptosis assays performed by flow cytometry. Continuous wave EPR spectra of RPE cells and TREPR of acidified synthetic melanin suggest that increased melanin aggregation provides an increase in photoprotection in the RPE cells that are relatively less susceptible to blue light-induced apoptosis.     

Performance of existing diagnosis/classification criteria for Behcet's disease in Iranian patients: analysis of 5666 patients and 2406 controls

Aim: To analyse the performance of existing diagnosis/classification criteria for Behcet's disease (BD) in Iranian patients. There are 13 sets: Curth (1946), Hewitt (1969), Mason and Barnes (1969), Hewitt revised (1971), Japan (1972), Hubault and Hamza (1974), O'Duffy (1974), Cheng and Zhang (1980), Dilsen (1986), Japan revised (1988), International (1990), Iran (1993), Classification Tree (1993), and Dilsen revised criteria (2000). Methods: All patients from the Behcet's Disease Registry (5666) and control patients (2406) entered the study. Sensitivity, specificity and accuracy were calculated. Results: The most sensitive was Curth criteria with (99.7%), followed by Classification Tree (97.3%), Zhang (93.5%), Iran (91.4%), Japan revised (86.4%), Japan (85.3%), Dilsen (83.7%), Hubault and Hamza (81.6%), Dilsen revised (81.2%), International criteria (79.8%), Hewitt (73.8%), O'Duffy (70.7%), and Masson and Barnes (65.7%). The most specific was Masson and Barnes (99.6%), followed by the International criteria (98.3%), Dilsen revised (98.2%), O'Duffy (97.6%), Japan (97.1%), Japan revised (97%), Classification Tree (96.7%), Hewitt (95.8%), Iran (95.8%), Zhang (92.4%), Dilsen (91.4%), Hubault (90.8%), and Curth (78.6%). The most accurate criteria was Classification Tree (97.1%), followed by Curth (93.4%), Zhang (93.1%), Iran (92.7%), Japan revised (89.6%), Japan (88.8%), Dilsen revised (86.2%), Dilsen (86%), International criteria (85.3%), Hubault (84.3%), Hewitt (80.4%), O'Duffy (78.8%), and Mason and Barnes (75.8%). Discussion: Among the existing criteria, the best to classify Iranian patients is the Classification Tree. The second most accurate is Curth criteria. The difference is statistically significant. Further, Curth criteria is not optimized, having very high sensitivity and low specificity.     

Investigating effects of hydroalcoholic extract of saffron on sex hormones in female rats undergoing chemotherapy with cyclophosphamide

Cyclophosphamide is an antineoplastic medicine that causes disorder in functions of the body systems. Thus, the purpose of this study is to investigate the effect of hydroalcoholic extract of saffron on improving the complications of cyclophosphamide on sex hormones. Fifty-six adult female Wistar rats were randomly divided into seven groups; control, sham (received distilled water, solvent extract, and drug), experimental groups 1, 2, and 3 (received cyclophosphamide (5 mg/kg/bw) + hydroalcoholic extract of saffron (2, 1, and 0.5 g/kg/bw), experimental group 4 (saffron 2 g/kg/bw), and experimental group 5 (cyclophosphamide 5 mg/kg/bw). Cyclophosphamide was given intraperitoneally, and extract by gavage was prescribed for 21 days. At the end of the experiment, after blood and preparation of serum, ELISA method was used for measuring the estrogen, progesterone, FSH, and LH hormones. Data and LSD test were analyzed with SPSS software (version 18). Results show that the concurrent use of low-dose cyclophosphamide and saffron extract can reduce toxic effect of cyclophosphamide on pituitary-gonadal axis and cause estrogen to be produced.