Investigation of the Role of Plasticizers in Film-forming Coats for Protecting Cooled Meat

As a result of theoretical studies on problems of protection and prolongation of storage terms of meat, it was revealed, that one of promising directions is to use protecting coats, based on natural biopolymers.The topicality of this study is in studying film-forming coats, based on natural polysaccharides, because they have high mechanical indices, absence of a smell, taste and are subjected to biological destruction. For regulating mechanical properties, the composition of film-creating coats is added with plasticizers of different origins.The aim of this work is in describing characteristics of food films, based on carrageenan, sodium alginate and plasticizers of different origins.There were mechanical, rheological properties of protecting coats. The comparative characteristic of these properties, depending on an added plasticizer, was realized. The type and mechanisms of interaction of components of the film-forming coat and plasticizers were completely described. The viscosity of the film-forming coat with a plasticizer has less values comparing with other solutions. Adding plasticizers resulted in increasing the film elasticity, but at the same time some increase of the firmness was observed.Film-forming coats with adding a plasticizer had a higher limit of fluidity, so they were firmer than complex film-forming coats without a plasticizer. From the other side, deformation values of film-forming coats without adding a plasticizer were higher than ones of complex film-forming coats with adding a plasticizer, because they were firmer.The study of physical properties of developed film-forming coats, based on hydrocolloids, demonstrated that coats with a plasticizer have more gas permeability.According to the results, obtained at experiments it was established, that the film-forming coat, based on sodium alginate, carrageenan and glycerin, has best mechanical, physical and rheological indices

Gene Therapy in Cardiac Arrhythmias

Gene therapy has progressed from a dream to a bedside reality in quite a few human diseases. From its first application in adenosine deaminase deficiency, through the years, its application has evolved to vascular angiogenesis and cardiac arrhythmias. Gene based biological pacemakers using viral vectors or mesenchymal cells tested in animal models hold much promise. Induction of pacemaker activity within the left bundle branch can provide stable heart rates. Genetic modification of the AV node mimicking beta blockade can be therapeutic in the management of atrial fibrillation. G protein overexpression to modify the AV node also is experimental. Modification and expression of potassium channel genes altering the delayed rectifier potassium currents may permit better management of congenital long QT syndromes. Arrhythmias in a failing heart are due to abnormal calcium cycling. Potential targets for genetic modulation include the sarcoplasmic reticulum calcium pump, calsequestrin and sodium calcium exchanger.Lastly the ethical concerns need to be addressed

Na/K pump regulation of cardiac repolarization: Insights from a systems biology approach

The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the Systems Biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most\ud important ionic mechanisms in regulating key properties of cardiac repolarization and its rate-dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies

Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations.

Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity. As a proof of principle, we evaluated extensively lipid membrane partitioning of d-sotalol, well-known blocker of a cardiac potassium channel Kv11.1 encoded by the hERG gene, with reported substantial proclivity for arrhythmogenesis. We developed the positively charged (cationic) and neutral d-sotalol models, compatible with the biomolecular CHARMM force field, and subjected them to all-atom molecular dynamics (MD) simulations of drug partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics and kinetics of their translocation and thus putative propensities for hydrophobic and aqueous hERG access. We found that only a neutral form of d-sotalol accumulates in the membrane interior and can move across the bilayer within millisecond time scale, and can be relevant to a lipophilic channel access. The computed water-membrane partitioning coefficient for this form is in good agreement with experiment. There is a large energetic barrier for a cationic form of the drug, dominant in water, to cross the membrane, resulting in slow membrane translocation kinetics. However, this form of the drug can be important for an aqueous access pathway through the intracellular gate of hERG. This route will likely occur after a neutral form of a drug crosses the membrane and subsequently re-protonates. Our study serves to demonstrate a first step toward a framework for multi-scale in silico safety pharmacology, and identifies some of the challenges that lie therein

The role of Volatile Anesthetics in Cardioprotection: a systematic review.

This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery

Investigating the protective role of the natural hormone Melatonin, in reducing drug-induced cardiotoxicity in the therapy of chronic diseases

Heart failure (HF) is a highly complex disorder and a major end-point of cardiovascular diseases (CVD). The pathogenesis of HF is mostly unresolved but involves interplay between cardiac structural and electrical remodelling, metabolic alterations, cell death and altered gene expression. Mitochondrial dysfunction and HF are common complications of chronic treatment from diverse groups of drugs, in particular anticancer drugs such as doxorubicin (DOX). Treatment of animals and cardiomyocytes with cardiotoxic chemicals such as β-adrenergic receptor agonists (such as isoproterenol) induces cardiac dysfunction and HF. Previous work done by the group have identified the pineal hormone melatonin was protective against stress-induced cardiac arrhythmias and simulated heart failure in cardiomyocytes in vitro. Melatonin synthesis is also dramatically decreased with age and in patients with CVD. The aim of the present project was to better understand the pathogenesis of druginduced cardiac dysfunction and delineate the role of melatonin in cardioprotection in H9c2, a model rat cell line in vitro. Using the Seahorse XF analyser method, it was demonstrated that commonly used medication for chronic diseases such as amiodarone, amitriptyline, and statins all caused altered mitochondrial dysfunction. In addition, cardiotoxic chemicals (isoproterenol, hydrogen peroxide, DOX) altered oxidative phosphorylation and glycolysis in living cardiomyocyte-derived H9c2 cells; these deleterious metabolic changes were ameliorated by melatonin. Flowcytometry and Alamar Blue staining methods demonstrated that DOX robustly induced apoptosis in H9c2 cells (~30%) which was reversed by melatonin. Doxorubicin-induced stress in H9c2 cells dramatically altered gene expression in several key signalling pathways integral in cardiac function and disease. These included mitochondrial metabolism (UCP2, PPARɣ, Drp1, Mfn1, Parp 1, Parp2, Sirt3 and Cav3), apoptosis (Bcl2 and Bcl-xL), cardiac electrophysiology and arrhythmia (Scn5a, SERCA2a), calcium handling (SERCA2a) and cardiac remodelling (Myh7, ms1). Melatonin pre-treatment attenuated or completely blocked this DOX-induced alteration in gene expression in cardiomyocytes. In conclusion, the present result demonstrated for the first time that melatonin is cardioprotective against drug-induced cardiotoxicity and apoptosis via modifying diverse heart failure-related signalling pathways. This provides novel insight on the possible use of melatonin as an adjunct intervention in several therapies including anti-cancer

Crosslinked agarose encapsulated sorbents resistant to steam sterilization. Preparation and mechanical properties

The application of agarose in hemoperfusion is hampered by the lack of a suitable sterilization method. A technique has been developed for the crosslinking of agarose encapsulated sorbents by the reaction with 1,3-dichloro-2-propanol (DCP) under strong alkaline conditions. A twofold molar excess of DCP with respect to agarose and an equimolar amount of sodium hydroxide at a concentration of 0.3 mol/L with a reaction time of 1-4 h at 50°C are found to be the optimal conditions. The compressive strength of crosslinked beads is increased by a factor of 4. Agarose capsules are found to degrade by the influence of Y radiation, but are resistant to steam sterilization at 134°C during at least 30 min when crosslinked

Acute Flecainide Toxicity Treated with Intravenous Lipid Emulsion

Flecainide is a Vaughn-Williams class IC antiarrhythmic used in the treatment of supraventricular tachycardias including atrial fibrillation. While overdose is rare, its negative effects on cardiac inotropy and conduction pathways can be readily fatal. This is further complicated by the redistribution of the drug out of the plasma and deposition in tissue, rendering reversal by sodium bicarbonate (the standard first line treatment agent) relatively ineffective. A case study of the successful treatment of hemodynamic collapse using sodium bicarbonate in conjunction with intravenous lipid emulsion (ILE) in a patient who ingested a large amount of flecainide in a suicide attempt will be discussed