Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC) affects millions in endemic areas and is presenting in growing numbers in the USA and European countries due to migration currents. Clinical progression, length of survival and overall prognosis are significantly worse in CCC patients when compared to patients with dilated cardiomyopathy of non-inflammatory etiology. Impairment of energy metabolism seems to play a role in heart failure due to cardiomyopathies. Herein, we have analyzed energy metabolism enzymes in myocardium samples of CCC patients comparing to other non-inflammatory cardiomyopathies. We found that myocardial tissue from CCC patients displays a significant reduction of both myocardial protein levels of ATP synthase alpha and creatine kinase enzyme activity, in comparison to control heart samples, as well as idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. Our results suggest that CCC myocardium displays a selective energetic deficit, which may play a role in the reduced heart function observed in such patients

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy

In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance. Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF. Sixteen patients were included (age 47.9 +/- A 11.5 years; 12 males, LVEF 28.6 +/- A 8.4%). Seven patients showed improved LVEF (9.7 +/- A 3.1%), and nine patients did not show improved LVEF (-3.4 +/- A 3.9%). MPR improved significantly in responders (1.56 +/- A .23 to 1.93 +/- A .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- A .70 to 1.61 +/- A .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns). In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve

Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

This article summarizes advances in the synthesis of well-defined polypeptides and block copolypeptides. Traditional methods used to polymerize α-amino acid-N-carboxyanhydrides (NCAs) are described, and limitations in the utility of these systems for the preparation of polypeptides are discussed. Improved initiators and methods that allow polypeptide synthesis with good control over chain length, chain length distribution, and chain-end functionality are also discussed. Using these methods, block and random copolypeptides of controlled dimensions (including molecular weight, sequence, composition, and molecular weight distribution) can now be prepared. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide micelles, copolypeptide vesicles, and copolypeptide hydrogels is described. Many of these assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. © Springer-Verlag Berlin Heidelberg 2013