Background Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intraarticular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. Objectives To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. Selection criteria We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. Data collection and analysis We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. Main results We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD-0.40, 95% CI-0.58 to-0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates 1 Intra-articular corticosteroid for knee osteoarthritis (Review)

Membrane fission is essential in intracellular transport. Acyl-coenzyme As (acyl-CoAs) are important in lipid remodelling and are required for fission of COPI-coated vesicles. Here we show that CtBP/BARS, a protein that functions in the dynamics of Golgi tubules, is an essential component of the fission machinery operating at Golgi tubular networks, including Golgi compartments involved in protein transport and sorting. CtBP/BARS-induced fission was preceded by the formation of constricted sites in Golgi tubules, whose extreme curvature is likely to involve local changes in the membrane lipid composition. We find that CtBP/BARS uses acyl-CoA to selectively catalyse the acylation of lysophosphatidic acid to phosphatidic acid both in pure lipidic systems and in Golgi membranes, and that this reaction is essential for fission. Our results indicate a key role for lipid metabolic pathways in membrane fission.

In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Società Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).

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Brefeldin A (BFA) is a fungal metabolite that disassembles the Golgi apparatus into tubular networks and causes the dissociation of coatomer proteins from Golgi membranes. We have previously shown that an additional effect of BFA is to stimulate the ADP-ribosylation of two cytosolic proteins of 38 and 50 kDa (brefeldin A-ADP-riboslyated substrate (BARS)) and that this effect greatly facilitates the Golgi-disassembling activity of the toxin. In this study, BARS has been purified from rat brain cytosol and microsequenced, and the BARS cDNA has been cloned. BARS shares high homology with two known proteins, C-terminal-binding protein 1 (CtBP1) and CtBP2. It is therefore a third member of the CtBP family. The role of BARS in Golgi disassembly by BFA was verified in permeabilized cells. In the presence of dialyzed cytosol that had been previously depleted of BARS or treated with an anti-BARS antibody, BFA potently disassembled the Golgi. However, in cytosol complemented with purified BARS, or even in control cytosols containing physiological levels of BARS, the action of BFA on Golgi disassembly was strongly inhibited. These results suggest that BARS exerts a negative control on Golgi tubulation, with important consequences for the structure and function of the Golgi complex.The Golgi complex, which plays a key role in intracellular trafficking and sorting, is composed of a constellation of stacks of flat cisternae bound together through tubular-reticular connecting zones into an overall ribbon-like shape. There has always been great interest among cell biologists in understanding the molecular mechanisms responsible for Golgi architecture and dynamics. Unfortunately, although significant progress has recently been made by studying the process of disassembly and reassembly of the Golgi complex that occurs during treatments with toxins such as ilimaquinone (1) and brefeldin A (BFA) 1 (2) or during mitosis (3), the present knowledge of these processes is still fragmentary.The focus of this study is on the molecular factors involved in the Golgi disassembly induced by BFA, a fungal toxin that causes the massive transformation of Golgi stacks into a tubular-reticular network. The effects of BFA have been attributed to at least two mechanisms. One is the release of coat proteins, including the coatomer (a major protein complex involved in coat protein I (COPI)-coated vesicle formation) and the small GTP-binding protein ARF (ADP-ribosylation factor) (4, 5) from Golgi membranes. The second mechanism is the activation of the endogenous ADP-ribosylation of two cytosolic proteins of 38 kDa (glyceraldehyde-3-phosphate dehydrogenase, a multifunctional protein involved in several cellular processes), and 50 kDa (BARS, a protein of unknown function) (6 -8). The role of coatomer in preserving the Golgi structure has been attributed to its function as a major membrane scaffold protein (2), but the significance of the ADP-ribosylation of BARS and glyceraldehyde-3-phosphate dehydrogenase is less well understood. In a previous report, ...