The endothelium-derived relaxing factors nitric oxide (NO) and prostacyclin (PGI 2 ) are important antithrombotic, relaxant, and antiproliferative agents of the blood vessel wall that exert their intracellular effects primarily via cGMP-and cAMP-dependent protein kinases (cGK, cAK). However, no biochemical marker for their activity in the intact blood vessel is available except for transient increases in the concentration of cGMP and cAMP. Using Western blot analysis and specific antibodies, we show here that phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) at Ser239 (P Ser239 -VASP) in rabbit aorta was detectable only in segments with an intact endothelium, although at least one third of VASP is contained in the remaining vascular wall. In endothelium-denuded aorta, VASP phosphorylation was increased by the NO donor sodium nitroprusside (SNP). Levels of P Ser239 -VASP, in the presence of endothelium and either SNP or 8-bromo-cAMP, were maximal. VASP phosphorylation elicited by 8-bromo-cAMP was inhibited significantly by the cGK inhibitor Rp-8-Br-PET-cGMPS. Stimulated P Ser239 -VASP formation was fully reversible, reaching basal levels after 10 min of repeated washouts. Consistent with the important role that the NO/cGMP pathway plays in the formation of P Ser239 -VASP in rabbit aorta, inhibition of NO synthase by N -nitro-L-arginine methyl ester (L-NAME; 1 mM) or of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[3,4-a]quinoxalin-1-one (ODQ; 50 M) almost completely abolished P Ser239 -VASP formation in endothelium intact blood vessels. These data suggest that vascular P Ser239 -VASP is primarily regulated by the NO/cGMP pathway and may thus serve as a biochemical marker for the activity state of this essential pathway in endothelial function.

RhoA stimulates vascular tone by increasing smooth muscle Ca(2+) sensitivity, e.g., in atherosclerosis. This study was an investigation of the influence of oxidized LDL (OxLDL), which accumulates in atherosclerotic plaques, on vascular tone induced by angiotensin II (AngII), with particular emphasis on the RhoA pathway. OxLDL had no influence on unstimulated vascular tone of isolated rabbit aorta, but it potentiated contractile responses induced by AngII. The Ca(2+)-antagonist felodipin partially prevented potentiation of contractile responses, whereas the AT(1) receptor antagonist losartan blunted AngII responses in presence and in absence of OxLDL. Rho-kinase inhibition by Y27632 abolished potentiation of contractile responses, and RhoA inhibition by C3-like transferase partially prevented it, suggesting that OxLDL activated RhoA. Activation of RhoA was further analyzed by detection of its translocation to the cell membrane after stimulation with OxLDL. Western blot analysis of aorta homogenates, as well as direct visualization in cultured smooth muscle cells using confocal laser scan microscopy, revealed that OxLDL potently activated RhoA. The effect of OxLDL was mimicked by its compound lysophosphatidylcholine, and C3 inhibited both lysophosphatidylcholine and OxLDL-induced RhoA stimulation. In conclusion, OxLDL stimulates the RhoA pathway, resulting in potentiation of AngII-induced vasoconstriction. Lysophosphatidylcholine mimics the OxLDL effect, consistent with a causal role of this OxLDL compound. Stimulation of RhoA by OxLDL may contribute to vasospasm in atherosclerotic arteries.

rhBMP-2 is associated with a higher rate of general complications as well as retrograde ejaculation, HO, and cervical tissue swelling in spine fusion. There is a slightly increased risk of new onset of tumors, however, without statistical significance.

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Background Whole spine localizers (WS-loc) of magnetic resonance imaging (MRI) are performed for enumeration of the vertebrae but they can be also used for the evaluation of the spine. Purpose To assess the accuracy of fracture detection using WS-locs of MRI and compare the findings with standard high-resolution short tau inversion recovery (STIR) sequences, and to determine whether the review of WS-locs is useful and if additional information can be gained by assessing the thoracic spine section of the WS-locs. Material and Methods A total of 298 magnetic resonance (MR) examinations of the lumbar spine with WS-locs were evaluated. Two independent readers reviewed the images. In case of fracture detection, further characterization of the fracture was performed. To assess inter-reader agreement, unweighted Cohen's kappa with 95% confidence intervals (CI) and Phi coefficients were calculated. Results The study sample included 187 female and 111 male patients (age range = 65-94 years; median age = 75.0 years). The WS-locs detected 42 fractures of the lumbar spine and 36 of the thoracic spine. Inter-reader agreement for fracture detection in the lumbar and thoracic spine was strong (K = 0.87, 95% CI = 0.78-0.95, Phi = 0.87, and K = 0.88, 95% CI = 0.79-0.96, Phi = 0.88, respectively). Conclusion WS-locs from MR examinations of the lumbar spine provide a good diagnostic tool for the detection and evaluation of unsuspected vertebral fractures. WS-locs show strong inter-reader agreement for fracture detection in the thoracic and lumbar spine.

The use of platelet concentrates in spine fusion shows significantly decreased union rates compared with the control group. However, complication and revision rates were not significantly increased. The current data do not recommend the use of platelet concentrate in spine fusion.

Vertebral compression fractures are among the most common forms of manifestations of osteoporosis. Conservative treatment comprises adequate analgesia, osteoporosis medication and individualized physiotherapy or braces. Nevertheless, vertebral compression fractures frequently lead to persisting pain and decrease daily activity and quality of life. In these cases, kyphoplasty and vertebroplasty can be efficient treatment options. Vertebroplasty is a minimally invasive procedure, in which bone cement is filled into the vertebral body under fluoroscopic control. In most cases, this internal stabilization leads to a rapid reduction in pain. Kyphoplasty additionally aims to correct the kyphotic deformation of the broken vertebra via introducing and inflating a balloon catheter. There is broad clinical experience with both procedures. For kyphoplasty, randomized controlled trials showed significant improvements in pain and quality of life in patients undergoing kyphoplasty. However, cement leakages lead to rare but severe complications such as pulmonary embolism and nerve palsies.

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