THE REMODELING OF LEFT ATRIUM AND VASODILATION FACTORS CHANGES IN ISCHEMIC HEART FAILURE

Background. According to the national registries of European countries and epidemiological studies, the prevalence of chronic heart failure (CHF) among adults is 2,0-5,0%, and increases due to age, in people aged over 70 years old it is 10,0-20,0%.Objective. To find out the specific features of remodeling of the left atrium and change of vasodilation factors in ischemic heart failure with reduced and preserved left ventricular ejection fraction and to establish correlation relationships.Methods. A full clinical examination of 153 patients with CHF (105 men and 48 women) was conducted to achieve this objective. The surveyed patients underwent clinical examinations; spectrophotometric parameters: quantification of markers of vasodilation, metabolites of monoxide nitrogen – nitrates and nitrites with Gris reagent; content of endothelial nitric oxide synthase (eNOS) in serum - ELISA for the set of Nitric Oxide Synthase 3, Endothelial (NOS3) Human ELISA Kit (Cloud-Clone Corp, USA). Electrocardiographic (ECG) examination was conducted in 12 standard conventional leads on electrocardiograph by the Hungarian production Heart Screen 112 D.Results. The 1st group of the examined patients with reduced LV EF prevails III (significant) degree LA dilatation in 33 (70.21%) cases, II (moderate) degree of LA dilatation was determined in 14 (29.78%), and I (initial) degree was not defined at all. In the 2nd group of the patients with preserved LV EF mainly the II degree of LA dilatation was determined in 44 (44.51%) cases, and decreased LA dilation in 39 (36.79%) cases (p<0.01), and III degree of LA dilation was defined in 23 (21.69%) cases (p<0.01). In patients with stable coronary heart disease, complicated by heart failure with reduced LV EF and II degree of LA dilatation, eNOS levels in the serum was 449.00±39.91 pg/ml, whereas in patients with stable coronary heart disease, complicated by heart failure with preserved LV EF and II stage of LA dilatation – 673.56±50.98 pg/ml (p<0.01). At III stage of LA dilatation in patients of the 1st group level eNOS was 344.20±51.98 pg/ml in the patients of the 2nd group – 616.90±36.49 pg/ml (p<0.01). At the same degree and with LA dilation in the patients of the 2nd group eNOS was 750.27±99.85 pg/ml. Conclusions. The structural and functional changes of the left atrium and changing factors of vasodilation in patients with stable coronary artery disease of II-III functional classes complicated by heart failure of I-III functional classes are studied. It is established that in the examined patients with stable coronary heart disease complicated by heart failure with reduced left ventricular ejection fraction mainly III (significant) degree of dilatation of the left atrium was determined, while in patients with stable coronary heart disease, complicated by heart failure with preserved left ventricular ejection fraction mainly II (moderate) degree of dilation of the left atrium was determined. In comparison with the results of research among the patients with stable coronary heart disease, complicated by heart failure with reduced left ventricular ejection fraction, and a group of patients with preserved left ventricular ejection fraction, it was determined a significant decrease in eNOS, nitrites, total amount of nitrites and nitrates

Crowding Promotes the Switch from Hairpin to Pseudoknot Conformation in Human Telomerase RNA

Formation of a pseudoknot in the conserved RNA core domain in the ribonucleoprotein human telomerase is required for function. In vitro experiments show that the pseudoknot (PK) is in equilibrium with an extended hairpin (HP) structure. We use molecular simulations of a coarse-grained model, which reproduces most of the salient features of the experimental melting profiles of PK and HP, to show that crowding enhances the stability of PK relative to HP in the wild type and in a mutant associated with dyskeratosis congenita. In monodisperse suspensions, small crowding particles increase the stability of compact structures to a greater extent than larger crowders. If the sizes of crowders in a binary mixture are smaller than the unfolded RNA, the increase in melting temperature due to the two components is additive. In a ternary mixture of crowders that are larger than the unfolded RNA, which mimics the composition of ribosome, large enzyme complexes and proteins in E. coli, the marginal increase in stability is entirely determined by the smallest component. We predict that crowding can restore partially telomerase activity in mutants, which dramatically decrease the PK stability.Comment: File "JACS_MAIN_archive_PDF_from_DOC.pdf" (PDF created from DOC) contains the main text of the paper File JACS_SI_archive.tex + 7 figures are the supplementary inf

Susceptibility amplitude ratio for generic competing systems

We calculate the susceptibility amplitude ratio near a generic higher character Lifshitz point up to one-loop order. We employ a renormalization group treatment with $L$ independent scaling transformations associated to the various inequivalent subspaces in the anisotropic case in order to compute the ratio above and below the critical temperature and demonstrate its universality. Furthermore, the isotropic results with only one type of competition axes have also been shown to be universal. We describe how the simpler situations of $m$-axial Lifshitz points as well as ordinary (noncompeting) systems can be retrieved from the present framework.Comment: 20 pages, no figure

Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria

Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found

Conformational dynamics and internal friction in homopolymer globules: equilibrium vs. non-equilibrium simulations

We study the conformational dynamics within homopolymer globules by solvent-implicit Brownian dynamics simulations. A strong dependence of the internal chain dynamics on the Lennard-Jones cohesion strength ε and the globule size N [subscript G] is observed. We find two distinct dynamical regimes: a liquid-like regime (for ε ε[subscript s] with slow internal dynamics. The cohesion strength ε[subscript s] of this freezing transition depends on N G . Equilibrium simulations, where we investigate the diffusional chain dynamics within the globule, are compared with non-equilibrium simulations, where we unfold the globule by pulling the chain ends with prescribed velocity (encompassing low enough velocities so that the linear-response, viscous regime is reached). From both simulation protocols we derive the internal viscosity within the globule. In the liquid-like regime the internal friction increases continuously with ε and scales extensive in N [subscript G] . This suggests an internal friction scenario where the entire chain (or an extensive fraction thereof) takes part in conformational reorganization of the globular structure.American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

Left Ventricular Remodeling in Patients with Stable Angina Complicated by Heart Failure with Reduced and Preserved Ejection Fraction

Introduction. Chronic heart failure is one of the most common and serious diseases of cardiovascular system, resulting in permanent disability and significantly reducing the length and quality of life. Purpose of the study to find out the features of left ventricular remodeling in patients with stable angina of II-III functional class depending on the reduction or preserving of left ventricular ejection fraction. Materials and research methods. To achieve this objective was conducted a full clinical examination of 153 patients with CHF (105 men and 48 women, average age of patients being 68,80 ± 0,90 years) who were treated separately at the cardiology department for patients with arrhythmias of Vinnytsia Regional Clinical Center for Treatment and Diagnostics of cardiovascular diseases. All the patients were divided into 2 groups: first group consisted of patients with stable angina of II-III FC and heart failure with reduced LV EF (n = 47); second group – patients with stable angina of II-III FC and HF with preserved LV EF (n = 106). The control group comprised 30 healthy individuals. Results of the investigation and their discussion. In the examined patients with stable angina of II-III FC with HF of I-III FC with reduced LV EF (1 group) according to the results of echocardiography compared with healthy people was determined a significant increase in size of left atrium, the final systolic size, end- diastolic size, end-systolic volume, end-diastolic volume, end-systolic index volume, stroke volume, the thickness of the back wall of the left ventricle, interventricular septum thickness, left ventricular myocardial mass index, relative LV wall thickness (p < 0.01) and a significant decrease in ejection fraction (p < 0.01), indicating the presence of structural and functional changes in the myocardium and reduced inotropic function of the heart. In the examined patients with stable angina with heart failure of I-III FC (2 group) with preserved LV EF by echocardiography results were defined similarly structural and functional changes in the left ventricle. However, it is important that as a result of a comparison of echocardiographic indicators of patients of surveyed groups 1 and 2 were found the following changes: a significant increase in the size of left atrium, the final systolic size, end diastolic size, end systolic volume, end-diastolic volume index, end-systolic volume index, end-diastolic volume, index of left ventricular mass, relative wall thickness of the left ventricle (p < 0.01) and a significant decrease in ejection fraction (p < 0.01) in the presence of heart failure with reduced LV EF. In the examined patients with reduced and preserved LV EF prevailed a concentric LVH. In the examined patients with heart failure with reduced LV EF prevailed III (significant) degree of LVH (p < 0.01). However, in patients with heart failure with preserved LV EF in most cases were determined II (moderate) or less III (significant) degree of LVH (p < 0.01). The results indicate that the examined patients with reduced LV EF heart remodeling is due to more and more significant increase of the degree of LVH and cardiac remodeling, which has an adverse prognostic significance. Conclusions. A deeper study and understanding of left ventricular remodeling in chronic heart failure of ischemic origin enables a more accurate description of the disease and provides an adequate medical care to patients suffering from stable angina of II-III functional classes, complicated by heart failure with reduced and preserved left ventricular ejection fraction

THE REMODELING OF LEFT ATRIUM AND VASODILATION FACTORS CHANGES IN ISCHEMIC HEART FAILURE

Background. According to the national registries of European countries and epidemiological studies, the prevalence of chronic heart failure (CHF) among adults is 2,0-5,0%, and increases due to age, in people aged over 70 years old it is 10,0-20,0%. Objective. To find out the specific features of remodeling of the left atrium and change of vasodilation factors in ischemic heart failure with reduced and preserved left ventricular ejection fraction and to establish correlation relationships. Methods. A full clinical examination of 153 patients with CHF (105 men and 48 women) was conducted to achieve this objective. The surveyed patients underwent clinical examinations; spectrophotometric parameters: quantification of markers of vasodilation, metabolites of monoxide nitrogen – nitrates and nitrites with Gris reagent; content of endothelial nitric oxide synthase (eNOS) in serum - ELISA for the set of Nitric Oxide Synthase 3, Endothelial (NOS3) Human ELISA Kit (Cloud-Clone Corp, USA). Electrocardiographic (ECG) examination was conducted in 12 standard conventional leads on electrocardiograph by the Hungarian production Heart Screen 112 D. Results. The 1st group of the examined patients with reduced LV EF prevails III (significant) degree LA dilatation in 33 (70.21%) cases, II (moderate) degree of LA dilatation was determined in 14 (29.78%), and I (initial) degree was not defined at all. In the 2nd group of the patients with preserved LV EF mainly the II degree of LA dilatation was determined in 44 (44.51%) cases, and decreased LA dilation in 39 (36.79%) cases (p<0.01), and III degree of LA dilation was defined in 23 (21.69%) cases (p<0.01). In patients with stable coronary heart disease, complicated by heart failure with reduced LV EF and II degree of LA dilatation, eNOS levels in the serum was 449.00±39.91 pg/ml, whereas in patients with stable coronary heart disease, complicated by heart failure with preserved LV EF and II stage of LA dilatation – 673.56±50.98 pg/ml (p<0.01). At III stage of LA dilatation in patients of the 1st group level eNOS was 344.20±51.98 pg/ml in the patients of the 2nd group – 616.90±36.49 pg/ml (p<0.01). At the same degree and with LA dilation in the patients of the 2nd group eNOS was 750.27±99.85 pg/ml. Conclusions. The structural and functional changes of the left atrium and changing factors of vasodilation in patients with stable coronary artery disease of II-III functional classes complicated by heart failure of I-III functional classes are studied. It is established that in the examined patients with stable coronary heart disease complicated by heart failure with reduced left ventricular ejection fraction mainly III (significant) degree of dilatation of the left atrium was determined, while in patients with stable coronary heart disease, complicated by heart failure with preserved left ventricular ejection fraction mainly II (moderate) degree of dilation of the left atrium was determined. In comparison with the results of research among the patients with stable coronary heart disease, complicated by heart failure with reduced left ventricular ejection fraction, and a group of patients with preserved left ventricular ejection fraction, it was determined a significant decrease in eNOS, nitrites, total amount of nitrites and nitrates

The Content of Vasodilation Factors in Blood Serum at Different Levels of Systolic- Diastolic Dysfunction of Left Ventricular with Stable Stenocardia Complicated by Heart Failure

Introduction. Congestive heart failure (CHF) is still the most topical medical­and­social problem all around the world. It is the most common and life­threatening disease of the cardiovascular system, resulting in permanent disability, leads to permanent disability, and significant reduction of life in longevity and quality. Objective. To find out the the level of vasodilation factors in blood serum at different levels of systolic­diastolic dysfunction of left ventricular in patients with stable angina of II­III functional class, complicated by the heart failure with reduced fraction of left ventricular ejection. Materials and methods. To study the goal was conducted a full clinical examination of 47 patients with stable angina of II­III functional classes (FC), complicated by the heart failure (HF) І­ІІІ FC with LV EF ≤ 45.0 % (31 men and 16 women, the average age of the patients was 66.00 ± 1.50 years). In addition to complex clinical­laboratory and instrumental investigations that meet modern requirements, patients underwent quantification of markers vasodilation ­ nitrites (NO2­) and nitrate (NO3­), eNOS. ENOS content in blood serum was determined by ″Nitric Oxide Synthase 3, Endothelial (еNOS) Human ELISA Kit″ (Cloud­Clone Corp, USA). Results and discussion. Analysis of vasodilation levels at different types of diastolic dysfunction (DD) LV in­ dicates that at the delayed relaxation the average level of eNOS was 498.55 ± 42.80 pg/ml, which is significantly higher than restrictive type of DD LV (p < 0.01). In pseudonormal type DD LV the average level of eNOS was 407.24 ± 54.59 pg/ml, which is significantly higher than restrictive type of DD LV (p < 0.05). Conclusions. In patients with stable angina of II­III FC complicated by the systolic heart failure with reduced ejection fraction of left ventricular, in the majority was determined II (moderate) degree of systolic dysfunction of left ventricular. Carried correlation analysis between the levels of eNOS in serum and ejection fraction of left ventricular in examined patients with stable angina of II­III FC complicated by the heart failure with the reduced ejection fraction of left ventricular, led to the establishment of a direct correlation of weak force. In patients with stable angina of II­III FC complicated by the heart failure with the reduced ejection fraction of left ventricular were mainly determined pseudonormal and restrictive types of diastolic dysfunction of left ventricular. In examined patients is observed trend to reduction of vasodilating factors (such as eNOS, nitrites and nitrates) on the progression of stages of systolic­diastolic dysfunction of the left ventricular

Mechanism of pH-induced Release of Retinol from Retinol-Binding Protein

A hypothesis is proposed explaining the mechanism of pH-induced release of retinol from retinol-binding protein (RBP). A number of conservative positively charged side chains located on the retinol-binding face of the RBP molecule are involved in salt bridges with conservative negatively charged groups. At low pH these salt bridges are broken and the retinol-binding face of RBP holds from 8 to 12 positively charged groups, which can ensure a proper orientation of the RBP molecule relative to a negatively charged membrane, facilitating the release of retinol. The disruption of salt bridges and the electrostatic repulsion of positive charges can soften the structure of the molecule near the entrance to the retinol-binding pocket, which can trigger both the release of retinol and the transition of RBP to the molten globule state

Influence of the conserved disulphide bond, exposed to the putative binding pocket, on the structure and function of the immunoglobulin-like molecular chaperone Caf1M of Yersinia pestis.

The Yersinia pestis protein Caf1M is a typical representative of a subfamily of periplasmic molecular chaperones with characteristic structural and functional features, one of which is the location of two conserved cysteine residues close to the putative binding pocket. We show that these residues form a disulphide bond, the reduction and alkylation of which significantly increases the dissociation constant of the Caf1M-Caf1 (where Caf 1 is a polypeptide subunit of the capsule) complex [from a Kd of (4.77+/-0.50)x10(-9) M for the intact protein to one of (3.68+/-0.68)x10(-8) M for the modified protein]. The importance of the disulphide bond for the formation of functional Caf1M in vivo was demonstrated using an Escherichia coli dsbA mutant carrying the Y. pestis f1 operon. In accordance with the CD and fluorescence measurements, the disulphide bond is not important for maintenance of the overall structure of the Caf1M molecule, but would appear to affect the fine structural properties of the subunit binding site. A three-dimensional model of the Caf1M-Caf1 complex was designed based on the published crystal structure of PapD (a chaperone required for Pap pili assembly) complexed with a peptide corresponding to the C-terminus of the papG subunit. In the model the disulphide bond is in close proximity to the invariant Caf1M Arg-23 and Lys-142 residues that are assumed to anchor the C-terminal group of the subunit. The importance of this characteristic disulphide bond for the orchestration of the binding site and subunit binding, as well as for the folding of the protein in vivo, is likely to be a common feature of this subfamily of Caf1M-like chaperones. A possible model for the role of the disulphide bond in Caf1 assembly is discussed