ABSTRACT
Non-vitamin K antagonist oral anticoagulants (NOACs), which inhibit thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, edoxaban) have been introduced in several clinical indications. Although NOACs have a favourable benefit-risk profile and can be used without routine laboratory monitoring, they are associated-as any anticoagulant-with a risk of bleeding. In addition, treatment may need to be interrupted in patients who need surgery or other procedures. The objective of this article, developed by a multidisciplinary panel of experts in thrombosis and haemostasis, is to provide an update on the management of NOAC-treated patients who experience a bleeding episode or require an urgent procedure. Recent advances in the development of targeted reversal agents are expected to help streamline the management of NOAC-treated patients in whom rapid reversal of anticoagulation is required.
Subject(s)
Anticoagulants/adverse effects , Antithrombins/adverse effects , Emergency Medical Services/methods , Hemorrhage/chemically induced , Hemorrhage/therapy , Administration, Oral , HumansABSTRACT
Statins, inhibitors of hydroxymethylglutaryl coenzyme A reductase, are the mainstay of the treatment of hypercholesterolemia in patients with cardiovascular disease. Besides the effects on cholesterol synthesis, they also have other effects. Pleiotropic effects of statins have been noted as anti-inflammatory, immunomodulatory, antioxidant, anti-thrombotic and endothelium stabilizing. All the mentioned effects could have beneficial role in the systemic response to infection, i.e. sepsis, but also in other systemic inflammatory conditions. We give a review of pharmacological effects of statins and of trials investigating the effects of statins in acute inflammatory response and sepsis.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Sepsis/drug therapy , Animals , Humans , Inflammation/drug therapy , Sepsis/prevention & control , Shock, Septic/drug therapyABSTRACT
OBJECTIVES: Glycosylation of IgG was suggested to be important in the etiology of rheumatoid diseases. Most studies addressed the amount of galactose, but recently we showed that fucose is highly increased in the juvenile chronic arthritis. The objective of this study was to determine fucosylation of IgG heavy chains in patients with rheumatoid arthritis (RA). DESIGN AND METHODS: IgG was purified from sera of 29 RA patients and 17 matching controls using ammonium sulfate precipitation and ion exchange. Heavy chains were separated by denaturing polyacrylamide gel electrophoresis and their fucosylation analysed using fucose-specific UEA I lectin. RESULTS: Fucose was found to be approximately 40% increased in RA patients with very high statistical significance (p = 0.00095). CONCLUSIONS: Fucose on IgG heavy chains is significantly increased in patients with rheumatoid arthritis.
Subject(s)
Arthritis, Rheumatoid/immunology , Fucose , Glycosylation , Immunoglobulin Fc Fragments/blood , Immunoglobulin G/blood , Immunoglobulin Heavy Chains/blood , Arthritis, Rheumatoid/blood , Carbohydrate Sequence , Female , Humans , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin G/chemistry , Immunoglobulin Heavy Chains/chemistry , Middle Aged , Molecular Sequence Data , Oligosaccharides/chemistry , Reference ValuesABSTRACT
Oligosaccharide structures are attached to nearly all membrane and serum proteins, and their composition changes significantly in many diseases. We have analysed glycosylation of IgG heavy chains in 34 patients with juvenile chronic arthritis and 13 control individuals. IgG was purified from 0.7 ml of serum, separated by electrophoresis and transferred on to polyvinylidene difluoride (PVDF) membrane. Ricinus communis agglutinin (RCA I) and Bandeirea simplicifolia (BSA II) and Ulex europaeus (UEA I) lectins were used to measure galactose, N-acetylglucosamine and fucose, respectively. While there was no significant difference in average levels of galactose and N-acetylglucosamine, patients with juvenile chronic arthritis had 2.4 times more fucose attached to IgG heavy chains than control individuals. A different picture emerged when patients were divided into those with acute disease and those in remission. Patients in whom juvenile chronic arthritis was currently active had significantly lower levels of galactose than those in remission, in whom galactose levels were comparable to the control group. Fucose levels in both groups of patients were significantly higher than in the control group. These results show that whereas de-galactosylation is a good test to detect and measure the activity of juvenile chronic arthritis, increased fucosylation is a much more reliable measure for diagnosis of the disease itself.
