Timely topics in medicine. Cardiovascular diseases最新文献

The use of blood biomarkers is getting increasingly popular in the field of cerebrovascular diseases, since biomarkers might aid physicians in several steps of stroke evaluation. We will discuss whether stroke diagnosis might be possible using some specific brain biomarkers and if this approach will permit rapid referral of stroke patients to hospitals with acute treatments such as tissue plasminogen activator (t-PA) available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lyses and earlier restoration of blood flow, up to 40-50% of treated patients do not recanalize or do it too late, and between 6 and 15% suffer hemorrhagic transformations with high death rates. In the context of the neurovascular unit, t-PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema and hemorrhage. In humans, biomarkers such as matrix metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select patients at higher risk of hemorrhagic transformation, and high plasminogen activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus predicting clot-lyses resistance and poor outcome, have been recently identified. Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as C-reactive protein may accurately predict stroke mortality following reperfusion therapies. Finally, we will also show that genetic background of stroke patients may condition plasma levels of some of these biomarkers and influence therapeutic response in t-PA-treated patients.

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. To date, its pathogenetic mechanisms are largely unclear. Cognitive impairments in patients with type 2 diabetes have been associated both with vascular risk factors, such as hypertension and dyslipidemia, and with diabetes-related factors, such as glycemic control, duration of the disease and treatment modality. Studies that address these associations generally focus on statistical (in)dependence of certain risk factors in the association between type 2 diabetes and cognitive decline rather than the causality of the association, which, from a mechanistic point of view, is more relevant. In this review we describe the association between type 2 diabetes and cognitive dysfunction and dementia. Furthermore, potential determinants of impaired cognition in type 2 diabetes are addressed both from the perspective of statistical associations and from a mechanistic point of view.

The high incidence of cardiovascular diseases resulting from atherosclerosis, especially in individuals lacking classic risk factors, has spawned interest in the possibility of unrecognized risk factors, such as chronic bacterial infection. Long-standing low-grade infections, such as periodontal disease, have the potential to affect distant sites in the body by inducing host cells to release inflammatory mediators into the bloodstream. Inflammatory mediators are released by macrophages upon interaction with activated T-helper cells or upon direct recognition of bacterial antigens, and by nonimmune cells upon recognition of antigen through Toll-like receptors. One key mediator, interleukin-1 (IL-1) is released in response to bacterial infection and is known to have specific pro-atherogenic properties. Increased levels of IL-1 enhance vascular adhesion, vascular permeability, macrophage activation, endothelial and smooth muscle cell proliferation, and protease-induced plaque rupture - all key steps in the progression of atherogenesis. In a recent study, we demonstrated a profound reduction in the progression of atherosclerosis in IL-1 knockout mice. IL-1 holds potential as a target for future antiatherosclerotic therapies, although given its ubiquity in the body, this would not come without unwanted side effects, such as immunosuppression.

Patients with diabetes are at increased risk of mortality and morbidity from micro- and macrovascular complications. Landmark studies in type 1 and 2 diabetes have clearly shown that improved glycemic control leads to better outcomes. With the introduction of the General Medical Service contract, the England and Wales National Service Framework, and other schemes, there is a national drive to improve control in patients with diabetes. The treatment of diabetes was revolutionized shortly after the turn of the 20th century by the extraction and purification of insulin. Since methods to protract (i.e., prolong) the action of insulin were developed in the 1930s, little changed in this technology until the turn of this century. At this time there was renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, and so technology advanced again. Two new basal insulin analogues have come to the market: insulin glargine, which has been widely used for some years now, and detemir. This review describes the novel method of protraction employed by insulin detemir, discusses the possible therapeutic benefits of this method of protraction, and describes the findings of studies comparing insulin detemir with other currently available basal insulin preparations. It is not the intention of this paper to be a review of all the currently available long-acting insulin analogues.