The effect of combining bone morphogenetic proteins -2 and -6 on osteoblastic differentiation and bone

Bone morphogenetic proteins-2 and -7 (BMP-2 and -7) are the only two members of the BMP subfamily approved to date to be used in combination with collagen type I in orthopedic surgery, although other BMPs have proven to also be highly osteoinductive. All the osteogenic BMPs signal through Smad-1/-5/-8 phosphorylation, but they have different preferences for the BMP receptors they use. Very high supraphysiological doses of BMPs have been used in the clinics for the treatment of non-union fractures and spinal fusions. Besides the high cost of these treatments, safety concerns have been recently raised. Hence there is an active field in finding alternatives to the most classical collagen + BMP-2 system. The aim of this work was to study the effect of combining two osteogenic BMPs (-2 and -6) belonging to different groups within the subfamily, and with different affinities to the existing BMP receptors. Both the growth and osteoblastic differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) under these conditions were studied, as well as in vivo ectopic bone formation when the BMPs were combined with collagen type I sponges. We show that the effect of these two growth factors is additive and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines

Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies

The political economy of Japanese foreign direct investment in the US and the UK Supranational, national and local factors in locational decision making

SIGLEAvailable from British Library Document Supply Centre-DSC:D197018 / BLDSC - British Library Document Supply CentreGBUnited Kingdo