Internal and emergency medicine
-
Diabetic patients have an increased risk for cardiovascular complications with respect to the general population. Micro- and macrovascular complications such as nephropathy, retinopathy, atherosclerosis, and coronary artery disease are usually preceded by endothelial dysfunction, a condition characterized by impaired vasorelaxation resulting from reduced bioavailability of the endothelial mediator nitric oxide (NO). Nitric oxide is among endothelial mediators released by endothelial cells in response to insulin stimulation. ⋯ Each of these alterations may trigger endothelial dysfunction by multiple intracellular mechanisms including accelerated formation of advanced glycolysis end products, activation of protein kinase C, increased pro-inflammatory signaling, and impaired sensitivity of the PI 3-kinase signaling pathways. This review outlines the most important mechanisms by which insulin takes part in physiological regulation of endothelial function. Abnormal insulin signaling in endothelium under diabetic conditions and patho-physiological consequences on cardiovascular homeostasis will also be discussed.
-
The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. Heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates. ⋯ Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are presently being evaluated in clinical studies. The new generation anticoagulants include specific inhibitors of factor IIa, factor Xa (including pentasaccharides) and agents that interfere with tissue factor activity. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option.