Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase Comparison with unfractionated heparin

AbstractObjectivesWe examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment–elevated acute myocardial infarction (AMl).BackgroundActivated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro.MethodsAfter successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10).ResultsAdverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group).ConclusionsAdministration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients

Vaccines against periodontitis: a forward-looking review

Periodontal disease, as a polymicrobial disease, is globally endemic as well as being a global epidemic. It is the leading cause for tooth loss in the adult population and has been positively related to life-threatening systemic diseases such as atherosclerosis and diabetes. As a result, it is clear that more sophisticated therapeutic modalities need to be developed, which may include vaccines. Up to now, however, no periodontal vaccine trial has been successful in satisfying all the requirements; to prevent the colonization of a multiple pathogenic biofilm in the subgingival area, to elicit a high level of effector molecules such as immunoglobulin sufficient to opsonize and phagocytose the invading organisms, to suppress the induced alveolar bone loss, or to stimulate helper T-cell polarization that exerts cytokine functions optimal for protection against bacteria and tissue destruction. This article reviews all the vaccine trials so as to construct a more sophisticated strategy which may be relevant in the future. As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, CD4+, CD25+, FoxP3+) have also been introduced. Targeting not only a single pathogen, but polymicrobial organisms, and targeting not only periodontal disease, but also periodontal disease-triggered systemic disease could be a feasible goal