Vasopressors and Inotropes in the Treatment of Human Septic Shock: Effect on Innate Immunity?

Catecholamines have been suggested to modulate innate immune responses in experimental settings. The significance hereof in the treatment of human septic shock is unknown. We therefore sought if and how vasopressor/inotropic doses relate to pro-inflammatory mediators during treatment of septic shock. We prospectively studied 20 consecutive septic shock patients. For 3 days after admission, hemodynamic variables, lactate and plasma levels of interleukins (IL)-6 and 8, tumor necrosis factor (TNF)-α, and elastase-α1-antitrypsin were measured six hourly. Doses of vasoactive drugs were recorded. Of the 20 patients, nine died in the intensive care unit. Dobutamine doses were positively associated and related to TNF-α plasma levels, independently of disease severity, hemodynamics, and outcome, in multivariable models. Dopamine doses were positively associated with IL-6, and norepinephrine was inversely associated with IL-8 and TNF-α levels. Our observations suggest that catecholamines used in the treatment of human septic shock differ in their potential modulation of the innate immune response to sepsis in vivo. Dobutamine treatment may contribute to circulating TNF-α and dopamine to IL-6, independently of activated neutrophils. Conversely, norepinephrine may lack pro-inflammatory actions

The Complement Anaphylatoxin C5a Induces Apoptosis in Adrenomedullary Cells during Experimental Sepsis

Sepsis remains a poorly understood, enigmatic disease. One of the cascades crucially involved in its pathogenesis is the complement system. Especially the anaphylatoxin C5a has been shown to have numerous harmful effects during sepsis. We have investigated the impact of high levels of C5a on the adrenal medulla following cecal ligation and puncture (CLP)-induced sepsis in rats as well as the role of C5a on catecholamine production from pheochromocytoma-derived PC12 cells. There was significant apoptosis of adrenal medulla cells in rats 24 hrs after CLP, as assessed by the TUNEL technique. These effects could be reversed by dual-blockade of the C5a receptors, C5aR and C5L2. When rats were subjected to CLP, levels of C5a and norepinephrine were found to be antipodal as a function of time. PC12 cell production of norepinephrine and dopamine was significantly blunted following exposure to recombinant rat C5a in a time-dependent and dose-dependent manner. This impaired production could be related to C5a-induced initiation of apoptosis as defined by binding of Annexin V and Propidium Iodine to PC12 cells. Collectively, we describe a C5a-dependent induction of apoptotic events in cells of adrenal medulla in vivo and pheochromocytoma PC12 cells in vitro. These data suggest that experimental sepsis induces apoptosis of adrenomedullary cells, which are responsible for the bulk of endogenous catecholamines. Septic shock may be linked to these events. Since blockade of both C5a receptors virtually abolished adrenomedullary apoptosis in vivo, C5aR and C5L2 become promising targets with implications on future complement-blocking strategies in the clinical setting of sepsis

An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice

Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV

We report the STAR measurement of Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV. Using the event mixing technique, the Phi spectra and yields are obtained at mid-rapidity for five centrality bins in Au+Au collisions and for non-singly-diffractive p+p collisions. It is found that the Phi transverse momentum distributions from Au+Au collisions are better fitted with a single-exponential while the p+p spectrum is better described by a double-exponential distribution. The measured nuclear modification factors indicate that Phi production in central Au+Au collisions is suppressed relative to peripheral collisions when scaled by the number of binary collisions. The systematics of versus centrality and the constant Phi/K- ratio versus beam species, centrality, and collision energy rule out kaon coalescence as the dominant mechanism for Phi production.Comment: 6 pages, 3 figures, submitted to Phys. Rev. Let

Rapidity and centrality dependence of proton and antiproton production from 197Au + 197Au collisions at √SNN = 130 GeV

We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3