FANS ed osso

Per i FANS \ue8 ipotizzata da tempo una loro azione sull\u2019osso ed il loro ruolo inibitorio nella riparazione delle fratture la conferma, ma controverso \ue8 il ruolo nell\u2019osteoporosi. Dagli anni 90 vari studi dimostravano un effetto positivo sulla massa ossea di FANS e aspirina, ma in studi successivi di vario disegno (da 2.000 a 300.000 soggetti prospettici o retrospettivi) il rischio di frattura risul- tava aumentato a seconda dei FANS, ma mai con l\u2019aspirina. Non chiariti sono i meccanismi di azione sull\u2019osso. Sembra che i FANS inibiscano l\u2019osteoblastogenesi, ma anche la osteoclastogenesi, con un deterioramento delle competenze meccaniche, senza riduzione della massa ossea.The inhibitory action of the prostaglandin synthesis is the basis for a supposed action on the bone of the NSAIDs (Non Steroidal Anti In ammatory Drugs), some of the most used drugs. There are, however, few published data on this action, except for the inhibition of bone healing by the NSAIDs. In the late nineties some studies demonstrating a positive effect of the NSAIDs on bone mass were edited. The positive effect seemed more evident for propionic NSAIDs (ibuprofen, ketoprofen...) and ASA, mainly if in association with the COX-2 inhibitors. Few years later some clinical studies, variously designed (prospectic, retrospective, and case-control), based on large population samples (a range from about 2,000 to 300,000 subjects), demonstrated, unexpectedly, an increase of the fracture risk in the NSAIDs users. The risk resulted variable for different NSAIDs molecules, but there were not a concordance among the studies, except for a not increased risk for ASA. An increased risk of a second hip fracture after the rst fragility hip fracture in the NSAIDs users, dose- and time-dependent, has been recently demonstrated in two propensity-score matching studies on a large popula- tion data-base in Taiwan. The cellular and molecular effects of the NSAIDs on the bone tissue have not yet well clari ed. An inhibition of the osteoblastogenesis, but also of the osteoclastogenesis has been demonstrated with different NSAIDs used in cellular coltures. These evidences could explain the increased fracture risk due to a decrease of the biomechanical properties of the bone, without a decreased bone mass

Vertebroplasty and kyphoplasty for the treatment of thoracic fractures in osteoporotic patients : A finite element comparative analysis

Background: Vertebral compression fractures occur in the thoracolumbar junction, causing the collapse of the vertebral body. For their treatment, vertebroplasty and kyphoplasty are used, but it is still unknown which technique is to be preferred. Methods: Finite element models of the thoracic spine were developed to evaluate the outcomes of vertebroplasty and kyphoplasty. A mild and severe collapse of T10 treated with vertebroplasty or kyphoplasty was studied. Stresses on the endplates and intradiscal pressures were extrapolated to determine the stress distribution in the adjacent structures. Results: The validation ensured a correct stiffness and a proper kinematic of each functional spinal unit. The results demonstrated that a consolidation following vertebroplasty caused slight variations of intradiscal pressures and stresses. If a kyphoplasty was performed after a mild collapse of the vertebral body, a 25% stress reduction on endplates was found. In cases of severe collapse, when a partial height restoration was achieved, a 15% stress reduction was obtained, while with a full recovery of the anterior wall of the collapsed vertebra, there was a further reduction of 40%. Conclusions: To reduce the stresses on the adjacent endplates and the risk of fracture, the results suggest a kyphoplasty is to be preferred, trying to restore the initial vertebral body height

Correlates of spinal deforming index (SDI) in HIV-positive patients naive and on treatment

Methods HIV-infected subjects naive or on stable HAART were included. Vertebral deformities were identified using SDI (according to semiquantitative method by Genant), calculated by summing the deformity grades of all vertebrae (T4 to L4); pathological deformities are defined as follow: grade 1 between 20–25%, grade 2 between 26–40%, and grade 3 > >40%. According to WHO criteria, osteopenia and osteoporosis were diagnosed in patients having spine BMD calculated as -1 << T-score << -2.5 and T-score ≤≤2.5, respectively. The correlation between SDI and spine BMD was evaluated by univariate and multivariate linear regression. [Other variables considered: gender, age, current CD4 count, CD4 nadir, BMI, lipid parameters, alcohol intake, smoking habit, physical activity, family history for bone fracture, months of ARV exposure, and co-infection with hepatitis viruses; only the variables with p <<0.2 in univariate analyses were included in the final model.

Toll-like receptor stimulation induces higher TNF-alpha secretion in peripheral blood mononuclear cells from patients with hyper IgE syndrome

Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with `cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammatory cytokine responses to different TLR ligands. Here, we report the increase in pro-inflammatory cytokines TNF-alpha and IL-8, following TLR2 and TLR4 stimulation in a larger cohort of 25 additional patients with HIES, and provide a meta-analysis of the TLR data in HIES. Copyright (C) 2008 S. Karger AG, Basel

Biophysical stimulation of bone and cartilage : state of the art and future perspectives

Introduction: Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. Methods: A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. Results: Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. Discussion: The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. Conclusion: The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients

DNA Nucleobase Synthesis at Titan Atmosphere Analog by Soft X-rays

Titan, the largest satellite of Saturn, has an atmosphere chiefly made up of N2 and CH4 and includes traces of many simple organic compounds. This atmosphere also partly consists of haze and aerosol particles which during the last 4.5 gigayears have been processed by electric discharges, ions, and ionizing photons, being slowly deposited over the Titan surface. In this work, we investigate the possible effects produced by soft X-rays (and secondary electrons) on Titan aerosol analogs in an attempt to simulate some prebiotic photochemistry. The experiments have been performed inside a high vacuum chamber coupled to the soft X-ray spectroscopy beamline at the Brazilian Synchrotron Light Source, Campinas, Brazil. In-situ sample analyses were performed by a Fourier transform infrared spectrometer. The infrared spectra have presented several organic molecules, including nitriles and aromatic CN compounds. After the irradiation, the brownish-orange organic residue (tholin) was analyzed ex-situ by gas chromatographic (GC/MS) and nuclear magnetic resonance (1H NMR) techniques, revealing the presence of adenine (C5H5N5), one of the constituents of the DNA molecule. This confirms previous results which showed that the organic chemistry on the Titan surface can be very complex and extremely rich in prebiotic compounds. Molecules like these on the early Earth have found a place to allow life (as we know) to flourish.Comment: To appear in Journal of Physical Chemistry A.; Number of pages: 6; Number of Figures: 5; Number of Tables: 1; Number of references:49; Full paper at http://pubs.acs.org/doi/abs/10.1021/jp902824

Hereditary Deficiency of gp91(phox) Is Associated With Enhanced Arterial Dilatation Results of a Multicenter Study

Background-NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results-Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P = 0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P+/-0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8+/-mol/L; P<0.016) and lower in obese patients (9.3+/-11.0 mu mol/L; P<0.001) compared with healthy subjects (27.1+/-19.1 mu mol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R-s = 0.403, P<0.001) and platelet gp91(phox) (R-s = -0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R-s = -0.502, P<0.001) and isoprostanes (R-s = -0.513, P<0.001). Conclusion-This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial ton

Clinical and functional outcomes of the PCCP study : a multi-center prospective study in Italy

The standard surgical management of hip fractures is associated with tissue trauma and bleeding which are added to the fracture injury. The percutaneous compression plate (PCCP) is a minimally invasive device that has been demonstrated in previous studies to reduce postoperative complications and blood loss. This prospective, multi-center, observational study assessed clinical and functional outcomes with PCCP as treatment for trochanteric fractures. Patients with a stable or unstable proximal femoral fracture of type AO 31.A1 or 31.A2 were enrolled in eight hospitals in Italy. The primary outcome of interest was the recovery of the pre-fracture functional status at 1-year follow-up; secondary outcomes of interest included blood transfusions, surgical time, complications, and mortality. A total of 273 patients were enrolled. The ASA score was 3 or 4 in 72.5 % of patients. The mean surgical time was 44.1 min; the mean post-surgery blood transfusions was 0.9 units. At 1 year, 48 patients (17.6 %) died, 28 (10.2 %) were lost to follow-up, 4 patients (1.5 %) were excluded, hence 193 patients (70.3 %) were available for final evaluation. At the 1-year follow-up visit, 51.9 % of patients recovered or improved their pre-fracture modified Harris Hip Score, 49.1 % of patients improved or maintained their walking abilities, and 66.6 % of patients residing at home pre-surgery maintained their domicile. The overall mortality rate was 17.6 %. Major complications included two fracture collapses, one excessive sliding of the cephalic screw leading to a partial fracture collapse and one back-out of the diaphyseal screw. This study demonstrates that treatment of trochanteric fractures with PCCP gives good outcomes and significant advantages such as low blood loss, short surgical time, low risk of complications, and good functional recovery in the majority of the patients

Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV