Annals of medicine
-
Bleeding is a serious adverse drug reaction associated with warfarin therapy, often induced by interacting co-medication. ⋯ We conclude that co-medication in warfarin-treated in-patients is common and should be carefully evaluated to decrease the bleeding risk associated with warfarin therapy.
-
Preptin is a novel hormone that is co-secreted with insulin and amylin from the pancreatic beta-cells. Preptin increases glucose-mediated insulin secretion, while the binding of endogenous preptin by antipreptin antibodies decreases glucose-mediated insulin secretion. Thus, it appears to act as a physiological amplifier of glucose-mediated insulin secretion. Aim. In this study, we investigate whether plasma preptin levels are different in non-diabetic subjects and patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). ⋯ The present work suggests a potential role of preptin in the pathogenesis of T2DM.
-
Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%-0.05%. In Finland, four founder mutations constitute up to 70% of the known genetic spectrum of LQTS. In the present survey, we sought to estimate the actual prevalence of the founder mutations and to determine their effect sizes in the general Finnish population. ⋯ In Finland 1 individual out of 250 carries a LQTS founder mutation, which is the highest documented prevalence of LQTS mutations that lead to a marked QT prolongation.
-
Mast cells (MCs) are perivascularly located resident cells of hematopoietic origin, recognized as effectors in inflammation and immunity. Their subendothelial location at the boundary between the intravascular and extravascular milieus, and their ability to rapidly respond to blood- and tissue-borne stimuli via release of potent vasodilatatory, proteolytic, fibrinolytic, and proinflammatory mediators, render MCs with a unique status to act in the first-line defense in various pathologies. We review experimental evidence suggesting a role for MCs in the pathophysiology of brain ischemia and hemorrhage. ⋯ MCs were reported to play a role in the tissue plasminogen activator-mediated cerebral hemorrhages after experimental ischemic stroke, and to be involved in the expansion of hematoma and edema following intracerebral hemorrhage. Importantly, the MC-stabilizing drug cromoglycate inhibited MC-mediated adverse effects on brain pathology and improved survival of experimental animals. This brings us to a position to consider MC stabilization as a novel initial adjuvant therapy in the prevention of brain injuries in hypoxia-ischemia in new-borns, as well as in ischemic stroke and intracerebral hemorrhage in adults.
-
The multiligand receptor RAGE (receptor for advanced glycation end-products) is emerging as a central mediator in the immune/inflammatory response. Epidemiological evidence accruing in the human suggests upregulation of RAGE's ligands (AGEs, S100/calgranulins, high mobility group box-1 (HMGB1), and amyloid beta-peptide and beta-sheet fibrils) and the receptor itself at sites of inflammation and in chronic diseases such as diabetes and neurodegeneration. ⋯ Lastly, we consider findings from animal model studies suggesting that although tissue-damaging effects ensue from recruitment of the ligand-RAGE interaction, in distinct settings, adaptive and repair/regeneration outcomes appear to override detrimental effects of RAGE. As RAGE blockade moves further into clinical development, clarifying the biology of RAGE garners ever-increasing importance.