The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury.

(1) Background: The present study aims to investigate the effect of administration of Levosimendan and Exenatide in various concentrations, as well as of the coadministration of those agents in an ischemia-reperfusion injury isolated heart model. (2) Methods: After 30 min of perfusion, the hearts underwent a 30 min period of regional ischemia followed by a 120 min period of reperfusion. All animals were randomly divided into 12 experimental groups of nine animals in each group: (1) Control, (2) Sham, (3) Digox (Negative control, Digoxin 1.67 µg/min), (4) Levo 1 (Levosimendan 0.01 µg/min), (5) Levo 2 (Levosimendan 0.03 µg/mL), (6) Levo 3 (Levosimendan 0.1 µg/min), (7) Levo 4 (Levosimendan 0.3 µg/min), (8) Levo 5 (Levosimendan 1 µg/min), (9) Exen 1 (Exenatide 0.001 µg/min), (10) Exen 2 (Exenatide 0.01 µg/min), (11) Exen 3 (Exenatide 0.1 µg/min) and (12) Combi (Levosimendan 0.1 µg/mL + Exenatide 0.001 µg/min). The hemodynamic parameters were recorded throughout the experiment. Arrhythmias and coronary flow were also evaluated. After every experiment the heart was suitably prepared and infarct size was measured. Markers of myocardial injury were also measured. Finally, oxidative stress was evaluated measuring reactive oxygen species. (3) Results: A dose-dependent improvement of the haemodynamic response was observed after the administration of both Levosimendan and Exenatide. The coadministration of both agents presented an even greater effect, improving the haemodynamic parameters further than the two agents separately. Levosimendan offered an increase of the coronary flow and both agents offered a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction and myocardial injury was observed after administration of Levosimendan and Exenatide. The coadministration of both agents offered a further improving the above parameters. Levosimendan also offered a significant reduction of oxidative stress. (4) Conclusions: The administration of Levosimendan and Exenatide offers a significant benefit by improving the haemodynamic response, increasing the coronary flow and reducing the occurrence of arrhythmias, the size of myocardial injury and myocardial oxidative stress in isolated rat hearts.

Calcification Assessment of Bioprosthetic Heart Valve Tissues Using an Improved In Vitro Model.

Calcification is a recurrent problem in patients suffering from heart valve disease and it is the main cause of failure in biological heart valve prostheses. The development of reliable calcification tests that consider both the material properties of the prostheses and the fluid composition is of paramount importance for the effective testing and subsequent selection of new cardiovascular implants. In this article, a fast, reliable, and highly reproducible method for the assessment of the calcification potential of biomaterials was developed. The developed method simulated closely the chemical environment in vivo, where the supersaturation levels of calcium and phosphate remain constant. Seeded hydroxyapatite (HAP) crystal growth experiments were used as the reference system and compared to the mineralization kinetics and extent of frozen untreated bovine and porcine pericardium, and glutaraldehyde-fixed bovine pericardium. Untreated pericardial patches did not calcify in the supersaturated calcium phosphate solutions whereas glutaraldehyde-fixed bovine pericardial patches mineralized at the same conditions. The present work suggested that the loose collagenous serosa side of the pericardium mineralized at lower rates compared to its dense collagenous fibrous side. Concordant with these findings, the mineralization of bioprostheses may also be attributed, to the structural deterioration of collagen-rich tissues, induced by chemical treatment used to control in vivo structural stability and immunomodulation of the implants.

Binding ability of a thymine-functionalized oligolysine towards nucleic acids.

In this Letter, we investigated the binding properties towards nucleic acids of a thymine-functionalized oligolysine, composed of nucleobase-bearing amino acid moieties and underivatized l-lysine residues alternate in the backbone. The basic nucleopeptide proved to be well soluble in water and able to interact with both DNA and RNA, as suggested by circular dichroism, UV and surface plasmon resonance studies performed on the thymine-containing oligomer with both adenine-containing DNA (dA12) and RNA (rA12 and poly rA) molecules. In both cases the thymine-functionalized oligolysine was proven to form complexes characterized by a 1:1 T/A stoichiometric ratio, as evidenced by CD titration. UV melting experiments revealed that the complex formed between the homothymine oligolysine and rA12 RNA was more stable than the complex with dA12 DNA probably due to the additional H-bonding of the 2'-OH groups in RNA, that reinforces the overall interaction with the nucleopeptide. Finally, human serum stability assays were conducted on the thymine-bearing nucleopeptide which showed a half-life of 45min.

Synthesis of a thymine-functionalized nucleoamino acid for the solid phase assembly of cationic nucleopeptides.

In this work, we report the synthesis of a thymine-functionalized nucleoamino acid suitable for the solid phase synthesis of nucleopeptides. The monomer was obtained in solution starting from commercial compounds and after NMR ((1)H and (13)C) and ESIMS (positive ions) characterization it was used for the assembly of a cationic nucleopeptide obtained by sequentially introducing underivatized L-lysine units and nucleoamino acid monomers. After detachment from the resin, performed in acidic conditions, the oligomer was purified by HPLC and characterized by LC-ESIMS (positive ions) which confirmed the identity of the thymine-based nucleopeptide. The cationic nucleobase-containing peptide, well soluble in water, was studied by CD spectroscopy which allowed us to exclude any helical pre-organization of the nucleopeptide in the experimental conditions used. Furthermore, CD behavior of the oligomer at different temperatures was also studied as described in this work.