T cell responsiveness to IL-10 defines the immunomodulatory effect of costimulation blockade via anti-CD154 and impacts transplant survival.

Costimulation blockade (CoB)-based immunotherapy is a promising alternative to immunosuppression for transplant recipients; however, the current limited understanding of the factors that impact its efficacy restrains its clinical applicability. In this context, pro- and anti-inflammatory cytokines are being recognized as having an impact on T cell activation beyond effector differentiation. This study aims at elucidating the impact of direct IL-10 signaling in T cells on CoB outcomes.

The king's spice cabinet-Plant remains from Gribshunden, a 15th century royal shipwreck in the Baltic Sea.

Maritime archaeological investigations of the wreck of the medieval warship Gribshunden (1495), flagship of King Hans of Denmark and Norway, have revealed diverse artifacts including exotic spices imported from far distant origins: saffron, ginger, clove, peppercorns, and almond. The special circumstances of the vessel's last voyage add unique context to the assemblage. Gribshunden and an accompanying squadron conveyed the king, courtiers, noblemen, and soldiers from Copenhagen to a political summit in Kalmar, Sweden.

Catabolism of the Lipofuscin Cycloretinal by MsP1.

Age-related macular degeneration (AMD) is a debilitating eye disease that tends to affect people over the age of 55. Lipofuscins are autofluorescent, toxic byproducts of the visual cycle thought to contribute toward the progression of the disease. Targeting the accumulation of lipofuscin through catabolism may serve as a method for the early treatment of AMD.

Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety.

The biosynthesis of the azinomycins involves the conversion of glutamic acid to an aziridino[1,2-]pyrrolidine moiety, which together with the epoxide moiety imparts anticancer activity to these agents. The mechanism of azabicycle formation is complex and involves at least 14 enzymatic steps. Previous research has identified -acetyl-glutamate 5-semialdehyde as a key intermediate, which originates from protection of the amino terminus of glutamic acid and subsequent reduction of the γ-carboxylate.

Biocatalysis with the milk protein β-lactoglobulin: promoting retroaldol cleavage of α,β-unsaturated aldehydes.

Enzymes with a hydrophobic binding site and an active site lysine have been suggested to be promiscuous in their catalytic activity. β-Lactoglobulin (BLG), the principle whey protein found in milk, possesses a central calyx that binds non-polar molecules. Here, we report that BLG can catalyze the retro-aldol cleavage of α,β-unsaturated aldehydes making it a naturally occurring protein capable of catalyzing retro-aldol reactions on hydrophobic substrates.

Transseptal transcatheter coil embolization of a symptomatic pulmonary arteriovenous aneurysm in a patient with hereditary hemorrhagic telangiectasia.

An atrial transseptal approach was used for embolization of a pulmonary arteriovenous aneurysm in a 56-year-old man with hereditary hemorrhagic telangiectasia. Two previous attempts at embolization of the aneurysm failed because of an inability to cannulate the feeding vessel. A transseptal puncture was performed to gain access to the left superior pulmonary vein allowing retrograde cannulation of the venous sac and successful coiling of the aneurysm without complications.

Cost implications of defibrillator lead failures.

Aims: The prevalence of lead failures is increasing with a growing population of implantable cardioverter defibrillator (ICD) recipients. The cost of managing defibrillator lead failures requires investigation.

Methods And Results: A retrospective cohort study of patients requiring lead replacement for defibrillator lead failure was performed.

Very late stent thrombosis immediately after recurrent inappropriate shock delivery by an implantable cardioverter defibrillator.

The case of a 49-year-old man who developed an ST segment elevation myocardial infarction because of very late stent thrombosis occurring in the immediate aftermath of a "storm" of recurrent inappropriate implantable cardioverter defibrillator (ICD) shocks caused by a fracture of a Medtronic Sprint Fidelis (Medtronic Inc., Minneapolis, MN) right ventricular lead is described. A causal relationship between recurrent ICD shocks and stent thrombosis is proposed.

Brain natriuretic peptide elevation and the development of atrial fibrillation following coronary artery bypass surgery.

The study was designed to determine whether the development of atrial fibrillation is associated with post-operative left ventricular dysfunction and subsequent left atrial stretch. We recruited 133 patients with well preserved pre-operative left ventricular function undergoing bypass surgery. Brain natriuretic peptide was measured at baseline, 24 and 48 h after the onset of cardiopulmonary bypass, and patients were monitored for 72 h after surgery.

Troponin T elevation after coronary bypass surgery: clinical relevance and correlation with perioperative variables.

Objective: Elevation in markers of myocardial necrosis is a common feature following coronary artery bypass surgery, but its relevance is unclear. The objective of this study was to evaluate the association between postoperative troponin T elevation, perioperative variables and clinical outcomes.

Methods: We evaluated 100 low-risk patients undergoing first-time elective on-pump coronary artery bypass surgery.

Inflammatory markers are not associated with outcomes following elective external cardioversion.

Background: Electrical cardioversion is a common modality of therapy for persistent atrial fibrillation. Unfortunately even if the cardioversion is initially successful many patients revert to atrial fibrillation. It has been proposed that there may be an inflammatory component to this arrhythmia.

Impact of vitamin E and C supplementation on serum adhesion molecules in chronic degenerative aortic stenosis: a randomized controlled trial.

Background: An inflammatory component has been identified in degenerative aortic stenosis (AS). The combination of vitamins E and C has been shown to have anti-inflammatory properties. The aim of this study was to determine the impact of the combination of vitamins C and E or vitamin C only on serum levels of cell adhesion molecules and C-reactive protein in patients with chronic degenerative AS, with or without concomitant coronary artery disease.

Vitamin E modulation of C-reactive protein in smokers with acute coronary syndromes.

Acute coronary syndromes are characterized by the expression of proinflammatory cytokines such as C-reactive protein (CRP). Sustained upregulation of inflammatory markers is associated with an adverse prognosis. Vitamin E is known to have significant anti-inflammatory properties and has been associated with a reduction in cardiovascular events in some studies of high-risk patients.

Anti-inflammatory effects of statins in patients with aortic stenosis.

Background: Aortic stenosis is an inflammatory process, as evidenced by increased tissue expression and serum levels of various endothelial cellular adhesion molecules. Aortic stenosis and atherosclerosis have many risk factors in common, including hypercholesterolemia. In atherosclerosis, statins lower cholesterol and display some anti-inflammatory activity.

Endothelial inflammation and thrombolysis resistance in acute myocardial infarction.

Background: Despite recent refinements to thrombolysis for acute myocardial infarction, a significant minority of patients still fail to reperfuse. There is no reliable predictor of this state of "thrombolysis resistance", but platelet and endothelial factors are believed to be important. Cell adhesion molecules are expressed by the endothelium when activated and their shed or soluble portion can be quantified in the peripheral serum, where they may be taken as a measure of endothelial activation.