Neuregulin-1β, Biomarkers of Inflammation and Myocardial Fibrosis in Heart Failure Patients

Neuregulin-1β (NRG-1) is an emerging biomarker of heart failure (HF). The mechanisms of its action in HF patients are yet  to be investigated. Cardioprotective and anti-inflammatory  effects of NRG-1 have been reported.Aim. To assess NRG-1 levels in HF patients and investigate the association between NRG-1 and biomarkers of inflammation and myocardial fibrosis.Material and Methods. NRG-1, biomarkers of inflammation and fibrosis (hsCRP, IL-6, sVCAM-1, MMP-9, Galectin-3, ST2, TGF-β) were assessed in 47 patients with HF and preserved ejection fraction (HFpEF); 39 patients with HF and reduced ejection  (HFrEF) and 40 healthy participants. The associations between  NRG-1 and biomarkers of inflammation and fibrosis, as well as  the composite outcomes of cardiovascular death and HF  hospitalisations were assessed.Results. Median NRG-1 levels in HFpEF were 0.969 (0.348; 1.932) ng/ml, in HFrEF – 0.63 (0.348; 1.932), in healthy participants 0.379 (0.195; 0.861) ng/ml, and was significantly higher in HFpEF compared to healthy volunteers (р=0.004). There was no  difference in NRG-1 concentration between HFpEF and HFrEF. In  HF patients, all biomarkers of inflammation and fibrosis were  higher than in controls. ST2, IL-6 and TGF-β were significantly higher in HFrEF compared to HFpEF patients, while hsCRP,  sVCAM-1, MMP-9, and Galectin-3 levels were comparable. In  HFpEF, NRG-1 was associated with hsCRP (rs=0.378, p=0.023) and IL-6 (rs=0.378, p=0.014). Median follow-up time in patients with HFpEF and in patients was 312 (236; 388) days, in HFrEF – 147 (98; 237) days. In HFpEF, 2 patients died and 19 were  hospitalized due to HF. In HFrEF, 10 deaths and 19  hospitalizations were registered. Kaplan-Mayer analysis showed that HFpEF patients with increased NRG-1 and IL-6 had higher  levels of HF hospitalisation (log rank test, р=0.046 and р=0.012, respectively). In a multivariable cox proportional hazard model,  the association between the NRG-1 and outcomes remained significant after adjustment for age, gender and NTproBNP but diminished when hsCRP and IL-6 were included in the model.Conclusion. NGR-1 level significantly higher in HFpEF compared to healthy participants, and comparable with NRG-1 concentrations in HFrEF. In HFpEF, NRG-1 was associated with biomarkers of inflammation and fibrosis. The prognostic value of NRG-1 in HF requires further investigations

Plasma Level’s of Neuregulin-1 in Healthy People

Aim. To determine the median levels of neuregulin-1 (NRG-1; endothelium-derived growth factor and the natural agonist of the ERBB3 and ERBB4 receptors) NRG-1 in healthy volunteers and to study the associations of NRG-1 levels with gender and age.Material and Methods. Ninety seven healthy participants were enrolled (median age of 44 [32-54], men 45 men [46.4%]). The following age groups were identified: 20-29 y.о. (n=20, men – 50.0%),  30-39  y.о.  (n=21,  men  –  52.4%),  40-49  y.о.  (n=22,  men  –  45.5%),  50-59  y.о. (n=22, men – 36.4%); 60-69 y.о. (n=12, men – 50.0%). Peripheral blood samples were collected at the time of enrolment, standard laboratory tests were performed, and NRG-1 levels were determined in the plasma samples by ELISA.Results. In the cohort of 97 healthy participants the median value of NRG-1 was 0.3 [0.121-2.24] ng/ml. NRG-1 levels did not differ significantly between men and women (p=0.145), indicating that NRG-1 levels are not influenced by gender. The levels of NRG-1 were similar in the different age groups: age 20-29 years=0.26 [0.17-0.37] ng/ml; age 30-39=0.24 [0.1-0.39] ng/ml; age 40-49=0.31 [0.19-1.15] ng/ml; age 50-59=0.37  [0.19-1.0] ng/ml; age 60-69=0.4 [0.13-0.81] ng/ml. Correlation analysis between NRG-1 levels and route blood measurements (haemoglobin, lipids, glucose, creatinine, and uretic acid) did not show significant associations.Conclusions. In this study, the median value of NRG-1 plasma levels were determined. The results of the study show that age and gender had no influence on NRG-1 values

Characterization of neutrino signals with radiopulses in dense media through the LPM effect

We discuss the possibilities of detecting radio pulses from high energy showers in ice, such as those produced by PeV and EeV neutrino interactions. It is shown that the rich radiation pattern structure in the 100 MHz to few GHz allows the separation of electromagnetic showers induced by photons or electrons above 100 PeV from those induced by hadrons. This opens up the possibility of measuring the energy fraction transmitted to the electron in a charged current electron neutrino interaction with adequate sampling of the angular distribution of the signal. The radio technique has the potential to complement conventional high energy neutrino detectors with flavor information.Comment: 5 pages, 4 ps figures. Submitted to Phys. Rev. Let

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target

Observation of the Askaryan Effect: Coherent Microwave Cherenkov Emission from Charge Asymmetry in High Energy Particle Cascades

We present the first direct experimental evidence for the charge excess in high energy particle showers predicted nearly 40 years ago by Askaryan. We directed bremsstrahlung photons from picosecond pulses of 28.5 GeV electrons at the SLAC Final Focus Test Beam facility into a 3.5 ton silica sand target, producing electromagnetic showers several meters long. A series of antennas spanning 0.3 to 6 GHz were used to detect strong, sub-nanosecond radio frequency pulses produced whenever a shower was present. The measured electric field strengths are consistent with a completely coherent radiation process. The pulses show 100% linear polarization, consistent with the expectations of Cherenkov radiation. The field strength versus depth closely follows the expected particle number density profile of the cascade, consistent with emission from excess charge distributed along the shower. These measurements therefore provide strong support for experiments designed to detect high energy cosmic rays and neutrinos via coherent radio emission from their cascades.Comment: 10 pages, 4 figures. Submitted to Phys. Rev. Let

Observations of the Askaryan Effect in Ice

We report on the first observations of the Askaryan effect in ice: coherent impulsive radio Cherenkov radiation from the charge asymmetry in an electromagnetic (EM) shower. Such radiation has been observed in silica sand and rock salt, but this is the first direct observation from an EM shower in ice. These measurements are important since the majority of experiments to date that rely on the effect for ultra-high energy neutrino detection are being performed using ice as the target medium. As part of the complete validation process for the Antarctic Impulsive Transient Antenna (ANITA) experiment, we performed an experiment at the Stanford Linear Accelerator Center (SLAC) in June 2006 using a 7.5 metric ton ice target, yielding results fully consistent with theoretical expectations.Comment: 4 pages, 5 figures, minor correction

Accelerator Measurements of the Askaryan effect in Rock Salt: A Roadmap Toward Teraton Underground Neutrino Detectors

We report on further SLAC measurements of the Askaryan effect: coherent radio emission from charge asymmetry in electromagnetic cascades. We used synthetic rock salt as the dielectric medium, with cascades produced by GeV bremsstrahlung photons at the Final Focus Test Beam. We extend our prior discovery measurements to a wider range of parameter space and explore the effect in a dielectric medium of great potential interest to large scale ultra-high energy neutrino detectors: rock salt (halite), which occurs naturally in high purity formations containing in many cases hundreds of cubic km of water-equivalent mass. We observed strong coherent pulsed radio emission over a frequency band from 0.2-15 GHz. A grid of embedded dual-polarization antennas was used to confirm the high degree of linear polarization and track the change of direction of the electric-field vector with azimuth around the shower. Coherence was observed over 4 orders of magnitude of shower energy. The frequency dependence of the radiation was tested over two orders of magnitude of UHF and microwave frequencies. We have also made the first observations of coherent transition radiation from the Askaryan charge excess, and the result agrees well with theoretical predictions. Based on these results we have performed a detailed and conservative simulation of a realistic GZK neutrino telescope array within a salt-dome, and we find it capable of detecting 10 or more contained events per year from even the most conservative GZK neutrino models.Comment: 15 pages, 16 figures, submitted to Phys. Rev.

NESTOR: A neutrino particle astrophysics underwater laboratory for the Mediterranean

Abstract An underwater neutrino astrophysics laboratory, to be located in the international waters off the Southwest of Greece, near the town of Pylos is now under construction. In the last two years a group of physicists from Greece and Russia have carried out two demonstration experiments in 4km deep water, counting muons and verifying the adequacy of the deep sea site. Plans are presented for a 100, 000 m 2 high energy neutrino detector composed of a hexagon of hexagonal towers, with 1176 optical detector units. A progress report is given and the physics potential of a siggle tower with 168 phototubes (currently under construction) is described

The Antarctic Impulsive Transient Antenna Ultra-high Energy Neutrino Detector Design, Performance, and Sensitivity for 2006-2007 Balloon Flight

We present a detailed report on the experimental details of the Antarctic Impulsive Transient Antenna (ANITA) long duration balloon payload, including the design philosophy and realization, physics simulations, performance of the instrument during its first Antarctic flight completed in January of 2007, and expectations for the limiting neutrino detection sensitivity. Neutrino physics results will be reported separately.Comment: 50 pages, 49 figures, in preparation for PR

VASCULAR INJURY CORRECTION IN ARTERIAL HYPERTENSION: FOCUS ON PERINDOPRIL

Risk factors are the cornerstone of the cardiovascular continuum concept. Arterial hypertension is one of major risk factors, which accounts for a substantial proportion of cardiovascular morbidity and mortality due to cardiovascular complications (CVC). The latter develop due to, among other reasons, the damage of the vascular component of cardiovascular system (CVS). Presently, the aims of antihypertensive treatment include not only control of blood pressure levels, but also CVC prevention. Antihypertensive medications of choice include the agents which also possess vasoprotective qualities