Interleukin-6 deficiency modifies the effect of high fat diet on myocardial expression of fatty acid transporters and myocardial lipids.

Chronic inflammation is a critical feature of obesity in the development of myocardial dysfunction. The observations that interleukin-6 (IL-6) is implicated in lipid and glucose homeostasis as well as its connection with the pathogenesis of insulin resistance might suggest the involvement of this cytokine in metabolic disorders of the failing heart. In the present study we aimed to assess the effects of IL-6 ablation in mice fed with normal and high fat diet on the myocardial expression of glucose and fatty acid transporting proteins, and to evaluate the paralleled alterations in lipid content.

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Objective: Reintegration of cancer patients into occupational life is an important social and economic factor. Data for the "return to work" in Head and Neck Cancer (HNC) patients are sparse, especially compared with other tumor entities.

Material And Methods: In a selective literature research, original articles dealing with the theme complex "return to work in patients with HNC", between 1997 and 2018 were included and analyzed.

Conformational changes underlying variation in the structural dynamics of materials confined at the nanometric scale.

Broadband dielectric and Raman spectroscopies combined with calorimetric measurements and DFT calculations have been used to investigate the molecular dynamics of the benzyl derivative of ibuprofen (Ben-IBU) incorporated into aluminum oxide (AAO) templates of various pore diameters (d = 20 nm and d = 80 nm). Time-dependent experiments on the material confined in pores of d = 20 nm revealed the occurrence of a low activation barrier kinetic process, that was manifested as a variation in the integral intensities of some characteristic vibrations of carboxylic and benzene moieties as well as a shift of the structural relaxation process. Complementary DFT computations enabled us to identify its molecular nature as originating from cis to trans like conformational change.

The relationships among monocyte subsets, miRNAs and inflammatory cytokines in patients with acute myocardial infarction.

Background: Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

Methods: In eighteen consecutive AMI patients (mean age 56.

Fluid therapy in non-septic, refractory acute decompensated heart failure patients - The cautious role of central venous pressure.

Purpose: Fluid therapy in congestive acute decompensated heart failure (ADHF) patients might be inappropriate and worsening the prognosis. The aim of our study was to analyze the effect of fluid administration on mortality in non-septic, ADHF patients with reduced ejection fraction.

Material And Methods: We analyzed 41 ADHF consecutive 'cold-wet' patients (mean age 69.

A Systematic Approach to Teaching Case Studies and Solving Novel Problems.

Both research and practical experience in education support the use of case studies in the classroom to engage students and develop critical thinking skills. In particular, working through case studies in scientific disciplines encourages students to incorporate knowledge from a variety of backgrounds and apply a breadth of information. While it is recognized that critical thinking is important for student success in professional school and future careers, a specific strategy to tackle a novel problem is lacking in student training.

KA-11, a Novel Pyrrolidine-2,5-dione Derived Broad-Spectrum Anticonvulsant: Its Antiepileptogenic, Antinociceptive Properties and in Vitro Characterization.

Recently, compound KA-11 was identified as a promising candidate for a new broad-spectrum anticonvulsant. This compound revealed wide protective activity across the most important animal models of seizures such as the maximal electroshock test (MES), the subcutaneous pentylenetetrazole test ( scPTZ), and the six-hertz test (6 Hz, 32 mA). Importantly, KA-11 was devoid of acute neurological activity, which was assessed by applying the chimney test (TD value higher than 1500 mg/kg).

Persistently elevated plasma heart-type fatty acid binding protein concentration is related with poor outcome in acute decompensated heart failure patients.

Background: The aim of the study was to determine clinical and prognostic role of repeated heart-type fatty acid binding protein (hFABP) measurements in acute decompensated HF (ADHF) patients.

Methods: In seventy-seven ADHF patients (III and IV NYHA class, mean age 70 ± 12.7 years, mean left ventricle ejection fraction [LVEF] 29.

Impact of Intermolecular Interactions, Dimeric Structures on the Glass Forming Ability of Naproxen, and a Series of Its Derivatives.

In this article, thermal properties, molecular dynamics, crystallization kinetics, and intermolecular interactions in pure naproxen (NAP), its amide (NH-NAP), and four esters (methyl, Met-NAP; isopropyl, Iso-NAP; hexyl, Hex-NAP; and benzyl, Ben-NAP) have been investigated using differential scanning calorimetry as well as broadband dielectric and Fourier transform infrared spectroscopies. We found that the modification of the NAP molecule by substituting a hydrogen atom from the hydroxyl group strongly inhibits the crystallization tendency of this active pharmaceutical ingredient (API) and simultaneously increases its glass forming ability (GFA). In this context, it is worthwhile to stress that pure naproxen and its amide crystallized very quickly, regardless of the cooling rate.

Very Small Embryonic-Like Stem Cells, Endothelial Progenitor Cells, and Different Monocyte Subsets Are Effectively Mobilized in Acute Lymphoblastic Leukemia Patients after G-CSF Treatment.

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease of lymphoid progenitor cells. ALL chemotherapy is associated with numerous side effects including neutropenia that is routinely prevented by the administration of growth factors such as granulocyte colony-stimulating factor (G-CSF). To date, the effects of G-CSF treatment on the level of mobilization of different stem and progenitor cells in ALL patients subjected to clinically effective chemotherapy have not been fully elucidated.

Studies on dynamics and isomerism in supercooled photochromic compound Aberchrome 670 with the use of different experimental techniques.

Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) and Broadband Dielectric (BD) spectroscopies were applied to investigate the thermal, structural, photochemical and dynamical properties of a fulgide-type photochromic compound, Aberchrome 670 (Ab670). In the original crystals, characterized by a pale yellow color, molecules take the E conformation. However, upon UV irradiation of either the crystalline or glassy compound, it isomerizes to the closed (C) form, characterized by the intense red tone.

Studying molecular dynamics of the slow, structural, and secondary relaxation processes in series of substituted ibuprofens.

In this paper, the molecular dynamics of a series of ester derivatives of ibuprofen (IBU), in which the hydrogen atom from the hydroxyl group was substituted by the methyl, isopropyl, hexyl, and benzyl moieties, has been investigated using Broadband dielectric (BD), Nuclear magnetic resonance (NMR), and Raman spectroscopies. We found that except for benzyl IBU (Ben-IBU), an additional process (slow mode, SM) appears in dielectric spectra in all examined compounds. It is worth noting that this relaxation process was observed for the first time in non-modified IBU (a Debye relaxation).

The role of platelets in the development and progression of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a multifactorial disease characterized by vasoconstriction, vascular remodeling, inflammation and thrombosis. Although an increasing number of research confirmed that pulmonary artery endothelial cells, pulmonary artery smooth muscle cells as well as platelets have a role in the pulmonary arterial hypertension pathogenesis, it is still unclear what integrates these factors. In this paper, we review the evidence that platelets through releasing a large variety of chemokines could actively impact the pulmonary arterial hypertension pathogenesis and development.

High-pressure dielectric studies on 1,6-anhydro-β-D-mannopyranose (plastic crystal) and 2,3,4-tri-O-acetyl-1,6-anhydro-β-D-glucopyranose (canonical glass).

Broadband Dielectric Spectroscopy was applied to investigate molecular dynamics of two anhydrosaccharides, i.e., 1,6-anhydro-β-D-mannopyranose, anhMAN (hydrogen-bonded system) and 2,3,4-tri-O-acetyl-1,6-anhydro-β-D-glucopyranose, ac-anhGLU (van der Waals material), at different thermodynamic conditions.

Anticoagulant Properties of Poly(sodium 2-(acrylamido)-2-methylpropanesulfonate)-Based Di- and Triblock Polymers.

Di- and triblock copolymers with low dispersity of molecular weight were synthesized using radical addition-fragmentation chain transfer polymerization. The copolymers contained anionic poly(sodium 2-acrylamido-2-methylpropanesulfonate) (PAMPS) block as an anticoagulant component. The block added to lower the toxicity was either poly(ethylene glycol) (PEG) or poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC).

Interleukin 6 Knockout Inhibits Aging-Related Accumulation of p53 in the Mouse Myocardium.

Interleukin 6 (IL6) and p53 are linked by mutual regulatory mechanisms and are both upregulated in aging. The aim of this study was to evaluate the effects of aging and IL6 on expression of p53 in the mouse heart. Male C57BL6/J wild-type and IL6 knockout mice at the age of 4-5 months (young adult) and 24-30 months (old) were used.

Evaluation of anticonvulsant and analgesic activity of new hybrid compounds derived from N-phenyl-2-(2,5-dioxopyrrolidin-1-yl)-propanamides and -butanamides.

Epilepsy is a chronic neurological disorder that is associated with various types of recurrent seizures, which are drug-resistant in about one third of patients. Moreover, anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic pain. Here, we investigated the anticonvulsant activity of six new hybrid compounds based on the pyrrolidine-2,5-dione scaffold in the 6 Hz corneal stimulation test with 44 mA stimulus intensity in mice, which is the model of pharmacoresistant seizures.

Increased platelet content of SDF-1alpha is associated with worse prognosis in patients with pulmonary prterial hypertension.

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression.

Unexpected Crossover in the kinetics of mutarotation in the supercooled region: the role of H-bonds.

Intra- and intermolecular studies on the molten L-sorbose have been carried out at variable temperature conditions to determine the crosover temperature (T ). In addition, isothermal time-dependent FTIR and Raman measurements were performed to probe the pace of mutarotation and activation energy of this reaction in the studied saccharide, which varied from 53-62 kJ/mol up to 177-192 kJ/mol below and above T , respectively. To explain the change in activation barrier for the mutarotation a complementary analysis using difference FTIR spectra collected around T  = 365 K in the hydroxyl region has been done.

LC-MS-based serum fingerprinting reveals significant dysregulation of phospholipids in chronic heart failure.

Cardiac and extracardiac lipid metabolism is known to be significantly altered in the course of the heart failure with reduced ejection fraction (HF-REF), however the precise mechanisms are not fully elucidated. The aim of the study was to use of untargeted metabolomics to identify and validate changes in the blood metabolites profile, occurring as a result of HF-REF development. The analyses were performed first in the derivation set (36 chronic HF-REF patients and 19 controls without the disease) and repeated in validation cohort (31 chronic HF-REF patients and 20 controls).

Anhydrosaccharides-A new class of the fragile plastic crystals.

In this paper, 1,6-anhydro-β-D-glucopyranose (anhGLU), 1,6-anhydro-β-D-mannopyranose (anhMAN), and 1,6-anhydro-β-D-galactopyranose (anhGAL), three new materials that form the Orientationally Disordered Crystal (ODIC) phase, have been thoroughly investigated using various experimental techniques. All measurements clearly indicated that these compounds possess a series of very interesting physical properties that are considerably different than those reported for ordinary plastic crystals. X-Ray diffraction investigations have revealed enormously long-range static correlations between molecules, reaching even 120 Å.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62).

The significance of diminished sTWEAK and P-selectin content in platelets of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative changes in pulmonary arteries. There is growing evidence suggesting that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P-selectin could be involved in PAH development and progression. Here we investigate whether circulating platelets may be a source of sTWEAK and contribute to diminished availability of sTWEAK and P-selectin in PAH patients.

Interleukin-6 Affects Aging-Related Changes of the PPARα-PGC-1α Axis in the Myocardium.

Aging is related to gradual increase of interleukin 6 (IL-6) plasma level that affects peroxisome proliferator-activated receptor (PPAR) expression. We evaluated age-related changes in cardiac expression of PPARα, its coactivator PGC-1α, and selected downstream proteins in mice with systemic IL-6 knockout (IL6KO). Male C57BL6/J wild-type (WT) and IL6KO mice were used at the age of 16-20 weeks (young) and 24-30 months (senescent).

Perioperative thrombocytopenia predicts poor outcome in patients undergoing transcatheter aortic valve implantation.

Purpose: To determine the time point at which thrombocytopenia after TAVI procedure is an indicator of the worst prognosis, with special consideration of perioperative platelet and coagulation activation as its potential causes.

Methods: Thirty two patients (mean age 78.5±7.