Background: Statins are recognised as the most effective lipid-lowering drugs. The main mechanism of action is the inhibition of 3-hydroxy- 3-methylglutaryl-coenzyme A reductase, which is a key ...enzyme in the cholesterol synthesis pathway. Statins also have additional effects, known as pleiotropic effects, which are mostly due to the inhibition of the formation of non-steroidal isoprenoids. The latter have important functions in the activation of many intracellular signalling pathways. Consequently, statins improve endothelial function, have anti-inflammatory and immunomodulatory activity, act as antioxidants, stabilize atherosclerotic plaques and influence haemostasis and thrombosis. The described mechanisms are particularly relevant in the protective activity of statins on the cardiovascular system, central nervous system, kidneys and many other organs. Conclusions: In the current article we review the pharmacological mechanisms of action, which contribute to the beneficial pleiotropic effects of statins. Described mechanisms are supported by the evidence obtained from clinical trials in the last decade.
Background: Structure and function of arterial system change with advancing age. The most important aging-induced changes of arterial system are: endothelial dysfunction, increased stiffness of ...arterial wall, an increase in arterial lumen size and increased intima-media thickness. As a consequence of these changes, arterial wall becomes more prone to the atherosclerotic process. Besides, the aged arterial wall causes undesirable hemodynamic effects, such as increased central arterial and pulse pressure. Age and arterial aging were ignored as risk factors for cardiovascular diseases. Recent studies have shown that aging is one of the most potent predictors of cardiovascular events. Conclusion: In the present review article ageassociated changes of arterial system and underlying mechanisms are described. Parameters, which can help define the structural and functional arterial wall changes, are also listed.
Background: Fabry disease is a rare X-chromosome linked disease. Due to gene mutation, activity of enzyme α galactosidase A is lowered or absent and sphingolipids are deposited in different organ ...cells. All males with gene mutation are affected but females too, due to X chromosome inactivation, can frequently be affected as well, although usually to a lesser extend. Disease is slowly progressive and there is an early dysfunction of several organs, specially endothelium, kidney, heart and central nervous system, which all leads to early death of the patient.Conclusions: Recently, a specific enzyme replacement therapy, based on recombinant technology, was discovered. Specific therapy is effective and safe. Due to a new therapy there was a need to set objective criteria when to start with enzyme replacement therapy, but also a need to more complex, multidisciplinary approach to those patients. This article is an initial proposal for systematic management of Fabry disease in our country.
Purpose. To investigate whether a chronic pro-thrombotic tendency, which may contribute to a high rate of atherothrombotic disease, is present in patients treated for continuous peritoneal dialysis ...(CAPD), and, if so, what its pattern is. We investigated this issue by jointly exploring all the systems involved, the coagulation and fibrinolytic systems and platelets. Methods. Markers of coagulation activation, markers of fibrinolysis activation, and standard fibrinolytic parameters and platelet aggregation induced by different agents were measured in 15 patients treated by CAPD and in 15 matched, healthy controls. All CAPD patients received erythropoietin, were in the stable condition, and did not have acute disease or malignancy. Results. CAPD patients had substantially (p < 0.001) increased levels of prothrombin fragments F1+2, disclosing a low-grade activation of the coagulation system. D-dimer was also significantly (p < 0.05) increased, whereas the levels of t-PA antigen and activity, PAI antigen and activity, and plasminogen were comparable to controls, suggesting that slight secondary (and not primary) activation of fibrinolysis due to coagulation activation took place. Patients had significantly (p < 0.05) elevated levels of fibrinogen. A study of platelet aggregation (induced by adenosine diphosphate, collagen, and epinephrine) did not show platelet hyperactivity in patients. Conclusions. We found that a pro-thrombotic tendency is present in the plasma of CAPD patients. The main reason for a pro-thrombotic state is chronic low-grade activation of the coagulation system and elevated levels of fibrinogen. The fibrinolytic system and platelets seemingly do not contribute to this pro-thrombotic tendency.
