Nitric oxide mediates interleukin-1 induced inhibition of glycosaminoglycan synthesis in rat articular cartilage

Interleek-1β (IL-1) is a key mediator of cartilage matrix degradation in osteoarthritis and rheumatoid arthritis. It was found that the IL-1-induced suppression of glycosaminoglycan (GAG) synthesis in rat articular cartilage occurred simultaneously with the accumulation of nitrite (a metabolite of nitric oxide (NO) in aqueous milieu) in the culture medium. NO-synthase inhibitors, L-NMMA and L-NIO, inhibited both these IL-1 effects. Dexamethasone suppressed GAG synthesis additively to IL-1, but did not alter nitrite accumulation. Three NO-donors (GEA 3175, SNAP and SIN-1) also had an inhibitory effect on cartilage GAG synthesis. Therefore, it is concluded that IL-1 induced suppression of GAG synthesis in rat articular cartilage is mediated by the production of NO

The importance of getting it right the first time

Non peer reviewe

Osteoporosis : the emperor has no clothes

Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.Peer reviewe

B fields in OB stars (BOB): Detection of a magnetic field in the He-strong star CPD-57{\deg} 3509

We report the detection of a magnetic field in the helium-strong star CPD-57 3509 (B2 IV), a member of the Galactic open cluster NGC3293, and characterise the star's atmospheric and fundamental parameters. Spectropolarimetric observations with FORS2 and HARPSpol are analysed using two independent approaches to quantify the magnetic field strength. A high-S/N FLAMES/GIRAFFE spectrum is analysed using a hybrid non-LTE model atmosphere technique. Comparison with stellar evolution models constrains the fundamental parameters of the star. We obtain a firm detection of a surface averaged longitudinal magnetic field with a maximum amplitude of about 1 kG. Assuming a dipolar configuration of the magnetic field, this implies a dipolar field strength larger than 3.3 kG. Moreover, the large amplitude and fast variation (within about 1 day) of the longitudinal magnetic field implies that CPD-57 3509 is spinning very fast despite its apparently slow projected rotational velocity. The star should be able to support a centrifugal magnetosphere, yet the spectrum shows no sign of magnetically confined material; in particular, emission in H{\alpha} is not observed. Apparently, the wind is either not strong enough for enough material to accumulate in the magnetosphere to become observable or, alternatively, some leakage process leads to loss of material from the magnetosphere. The quantitative spectroscopic analysis of the star yields an effective temperature and a logarithmic surface gravity of 23750+-250 K and 4.05+-0.10, respectively, and a surface helium fraction of 0.28+-0.02 by number. The surface abundances of C, N, O, Ne, S, and Ar are compatible with the cosmic abundance standard, whereas Mg, Al, Si, and Fe are depleted by about a factor of 2. This abundance pattern can be understood as the consequence of a fractionated stellar wind. CPD-57 3509 is one of the most evolved He-strong stars known.Comment: 15 pages, 11 figures. Accepted for publication in A&

Bioabsorbable Versus Metal Screw in the Fixation of Tibial Tubercle Transfer

Peer reviewe

Mechanical symptoms as an indication for knee arthroscopy in patients with degenerative meniscus tear : a prospective cohort study

Peer reviewe

Disk Partition Function and Oscillatory Rolling Tachyons

An exact cubic open string field theory rolling tachyon solution was recently found by Kiermaier et. al. and Schnabl. This oscillatory solution has been argued to be related by a field redefinition to the simple exponential rolling tachyon deformation of boundary conformal theory. In the latter approach, the disk partition function takes a simple form. Out of curiosity, we compute the disk partition function for an oscillatory tachyon profile, and find that the result is nevertheless almost the same.Comment: 17 pages, 2 figures. v4: discussion clarified, appendix added, conclusions unchanged; version to appear in J.Phys.

Does Compassion Predict Blood Pressure and Hypertension? The Modifying Role of Familial Risk for Hypertension

Background This study investigated (i) whether compassion is associated with blood pressure or hypertension in adulthood and (ii) whether familial risk for hypertension modifies these associations. Method The participants (N = 1112-1293) came from the prospective Young Finns Study. Parental hypertension was assessed in 1983-2007; participants' blood pressure in 2001, 2007, and 2011; hypertension in 2007 and 2011 (participants were aged 30-49 years in 2007-2011); and compassion in 2001. Results High compassion predicted lower levels of diastolic and systolic blood pressure in adulthood. Additionally, high compassion was related to lower risk for hypertension in adulthood among individuals with no familial risk for hypertension (independently of age, sex, participants' and their parents' socioeconomic factors, and participants' health behaviors). Compassion was not related to hypertension in adulthood among individuals with familial risk for hypertension. Conclusion High compassion predicts lower diastolic and systolic blood pressure in adulthood. Moreover, high compassion may protect against hypertension among individuals without familial risk for hypertension. As our sample consisted of comparatively young participants, our findings provide novel implications for especially early-onset hypertension

Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency

Introduction Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI. Methods Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography). Results Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p Conclusions In this model of stage 3-4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI.Peer reviewe