Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC

The seed laser system of the FERMI free-electron laser: design, performance and near future upgrades

Abstract An important trend in extreme ultraviolet and soft X-ray free-electron laser (FEL) development in recent years has been the use of seeding by an external laser, aimed to improve the coherence and stability of the generated pulses. The high-gain harmonic generation seeding technique was first implemented at FERMI and provided FEL radiation with high coherence as well as intensity and wavelength stability comparable to table-top ultrafast lasers. At FERMI, the seed laser has another very important function: it is the source of external laser pulses used in pump–probe experiments allowing one to achieve a record-low timing jitter. This paper describes the design, performance and operational modes of the FERMI seed laser in both single- and double-cascade schemes. In addition, the planned upgrade of the system to meet the challenges of the upgrade to echo-enabled harmonic generation mode is presented

Characterization of soft x-ray echo-enabled harmonic generation free-electron laser pulses in the presence of incoherent electron beam energy modulations

Echo-enabled harmonic generation free-electron lasers (EEHG FELs) are promising candidates to produce fully coherent soft x-ray pulses by virtue of efficient high-harmonic frequency up-conversion from ultraviolet lasers. The ultimate spectral limit of EEHG, however, remains unclear, because of the broadening and distortions induced in the output spectrum by residual broadband energy modulations in the electron beam. We present a mathematical description of the impact of incoherent (broadband) energy modulations on the bunching spectrum produced by the microbunching instability through both the accelerator and the EEHG line. The model is in agreement with a systematic experimental characterization of the FERMI EEHG FEL in the photon energy range 130\u2013210 eV. We find that amplification of electron beam energy distortions primarily in the EEHG dispersive sections explains an observed reduction of the FEL spectral brightness proportional to the EEHG harmonic number. Local maxima of the FEL spectral brightness and of the spectral stability are found for a suitable balance of the dispersive sections\u2019 strength and the first seed laser pulse energy. Such characterization provides a benchmark for user experiments and future EEHG implementations designed to reach shorter wavelengths

Towards jitter-free pump-probe measurements at seeded free electron laser facilities

X-ray free electron lasers (FEL) coupled with optical lasers have opened unprecedented opportunities for studying ultrafast dynamics in matter. The major challenge in pump-probe experiments using FEL and optical lasers is synchronizing the arrival time of the two pulses. Here we report a technique that benefits from the seeded-FEL scheme and uses the optical seed laser for nearly jitter-free pump-probe experiments. Timing jitter as small as 6 fs has been achieved and confirmed by measurements of FEL-induced transient reflectivity changes of Si3N4 using both collinear and non-collinear geometries. Planned improvements of the experimental set-up are expected to further reduce the timing jitter between the two pulses down to fs level

Tunability experiments at the FERMI@Elettra free-electron laser

FERMI@Elettra is a free electron-laser (FEL)-based user facility that, after two years of commissioning, started preliminary users' dedicated runs in 2011. At variance with other FEL user facilities, FERMI@Elettra has been designed to deliver improved spectral stability and longitudinal coherence. The adopted scheme, which uses an external laser to initiate the FEL process, has been demonstrated to be capable of generating FEL pulses close to the Fourier transform limit. We report on the first instance of FEL wavelength tuning, both in a narrow and in a large spectral range (fine- and coarse-tuning). We also report on two different experiments that have been performed exploiting such FEL tuning. We used fine-tuning to scan across the 1s–4p resonance in He atoms, at ≈23.74 eV (52.2 nm), detecting both UV–visible fluorescence (4p–2s, 400 nm) and EUV fluorescence (4p–1s, 52.2 nm). We used coarse-tuning to scan the M4,5 absorption edge of Ge (∼29.5 eV) in the wavelength region 30–60 nm, measured in transmission geometry with a thermopile positioned on the rear side of a Ge thin foil