Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis.

In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and on survival in the post-traumatic sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48 h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%), while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1st hit solely based on the common immuno-inflammatory parameters could be misleading.

Selective mass enhancement close to the quantum critical point in BaFe2(As1-x P x )2.

A quantum critical point (QCP) is currently being conjectured for the BaFe2(As1-x P x )2 system at the critical value x c ≈ 0.3. In the proximity of a QCP, all thermodynamic and transport properties are expected to scale with a single characteristic energy, given by the quantum fluctuations. Such a universal behavior has not, however, been found in the superconducting upper critical field H c2. Here we report H c2 data for epitaxial thin films extracted from the electrical resistance measured in very high magnetic fields up to 67 Tesla. Using a multi-band analysis we find that H c2 is sensitive to the QCP, implying a significant charge carrier effective mass enhancement at the doping-induced QCP that is essentially band-dependent. Our results point to two qualitatively different groups of electrons in BaFe2(As1-x P x )2. The first one (possibly associated to hot spots or whole Fermi sheets) has a strong mass enhancement at the QCP, and the second one is insensitive to the QCP. The observed duality could also be present in many other quantum critical systems.

Signatures of a magnetic field-induced unconventional nematic liquid in the frustrated and anisotropic spin-chain cuprate LiCuSbO4.

Modern theories of quantum magnetism predict exotic multipolar states in weakly interacting strongly frustrated spin-1/2 Heisenberg chains with ferromagnetic nearest neighbor (NN) inchain exchange in high magnetic fields. Experimentally these states remained elusive so far. Here we report strong indications of a magnetic field-induced nematic liquid arising above a field of ~13 T in the edge-sharing chain cuprate LiSbCuO4 ≡ LiCuSbO4. This interpretation is based on the observation of a field induced spin-gap in the measurements of the 7Li NMR spin relaxation rate T 1-1 as well as a contrasting field-dependent power-law behavior of T 1-1 vs. T and is further supported by static magnetization and ESR data. An underlying theoretical microscopic approach favoring a nematic scenario is based essentially on the NN XYZ exchange anisotropy within a model for frustrated spin-1/2 chains and is investigated by the DMRG technique. The employed exchange parameters are justified qualitatively by electronic structure calculations for LiCuSbO4.

Coupled multiple-mode theory for s± pairing mechanism in iron based superconductors.

We investigate the interplay between the magnetic and the superconducting degrees of freedom in unconventional multi-band superconductors such as iron pnictides. For this purpose a dynamical mode-mode coupling theory is developed based on the coupled Bethe-Salpeter equations. In order to investigate the region of the phase diagram not too far from the tetracritical point where the magnetic spin density wave, (SDW) and superconducting (SC) transition temperatures coincide, we also construct a Ginzburg-Landau functional including both SC and SDW fluctuations in a critical region above the transition temperatures. The fluctuation corrections tend to suppress the magnetic transition, but in the superconducting channel the intraband and interband contribution of the fluctuations nearly compensate each other.

Complex Field-Induced States in Linarite PbCuSO4(OH)2 with a Variety of High-Order Exotic Spin-Density Wave States.

Low-temperature neutron diffraction and NMR studies of field-induced phases in linarite are presented for magnetic fields H∥b axis. A two-step spin-flop transition is observed, as well as a transition transforming a helical magnetic ground state into an unusual magnetic phase with sine-wave-modulated moments ∥H. An effective J[over ˜]_{1}-J[over ˜]_{2} single-chain model with a magnetization-dependent frustration ratio α_{eff}=-J[over ˜]_{2}/J[over ˜]_{1} is proposed. The latter is governed by skew interchain couplings and shifted to the vicinity of the ferromagnetic critical point. It explains qualitatively the observation of a rich variety of exotic longitudinal collinear spin-density wave, SDW_{p}, states (9≥p≥2).

Systemic inhibition and liver-specific over-expression of PAI-1 failed to improve survival in all-inclusive populations or homogenous cohorts of CLP mice.

BACKGROUND: The role of plasminogen activator inhibitor type-1 (PAI-1) in abdominal sepsis remains elusive. OBJECTIVES: To study the influence of inhibition and over-expression of PAI-1 upon survival in cecal ligation and puncture (CLP) sepsis. METHODS: (i) Mice underwent moderate CLP and received 10 mg kg(-1) of either monoclonal anti-PAI-1 (MA-MP6H6) or control (MA-Control) antibody intravenously at 0, 18 or 30 h post-CLP. The 30-h treatment group was additionally stratified into mice predicted to survive (P-SUR) or die (P-DIE) based on IL 6 measured at 24 h post-CLP. (ii) PAI-1 expression was induced with pLIVE.PAI-1 plasmid administered 72 h pre-CLP. Blood was sampled for 5 days and survival was monitored for 28 days. RESULTS: MA-MP6H6 effectively neutralized active PAI-1 and fully restored fibrinolysis while PAI-1 over-expression was liver-specific and correlated with PAI-1 increase in the blood. Without stratification, MA-MP6H6 co-/post-treatment conferred no survival benefit. Prospective stratification (IL-6 cut-off: 14 ng mL(-1) ) suggested increased mortality by MA-MP6H6 treatment in P-SUR that reached 30% difference (vs. MA-Control; P < 0.05) after a retrospective cut-off readjustment to 3.3 ng mL(-1) for better P-SUR homogeneity. Subsequent prospective anti-PAI-1 treatment in P-SUR mice with 3.3 ng mL(-1) cut-off demonstrated a negative but statistically insignificant effect: mortality was higher by 17% after MA-MP6H6 vs. MA-Control. Over-expression of PAI 1 did not alter post-CLP survival. Neither PAI-1 inhibition nor over-expression meaningfully modified inflammatory response and/or organ function. CONCLUSIONS: Restoration of fibrinolysis in early abdominal sepsis was not beneficial and it may prove detrimental in subjects with the lowest risk of death, while preemptive PAI-1 up-regulation at the current magnitude was not protective.

Ca(2)Y(2)Cu(5)O(10): the first frustrated quasi-1D ferromagnet close to criticality.

Ca(2)Y(2)Cu(5)O(10) is built up from edge-shared CuO(4) plaquettes forming spin chains. From inelastic neutron scattering data we extract an in-chain nearest-neighbor exchange J(1)≈-170 K and the frustrating next-neighbor J(2)≈32 K interactions, both significantly larger than previous estimates. The ratio α=|J(2)/J(1)|=0.19±0.01 places the system close to the critical point α(c)=0.25 of the J(1)-J(2) chain but in the 1D ferromagnetic regime. We establish that the vicinity to criticality only marginally affects the dispersion and coherence of the spin-wave-like magnetic excitations but instead results in a dramatic T dependence of high-energy Zhang-Rice singlet excitation intensities.

Saturation field of frustrated chain cuprates: broad regions of predominant interchain coupling.

A thermodynamic method to extract the interchain coupling (IC) of spatially anisotropic 2D or 3D spin-1/2 systems from their empirical saturation field H(s) (T=0) is proposed. Using modern theoretical methods we study how H(s) is affected by an antiferromagnetic (AFM) IC between frustrated chains described in the J(1)-J(2)-spin model with ferromagnetic 1st and AFM 2nd neighbor in-chain exchange. A complex 3D-phase diagram has been found. For Li(2)CuO(2) and Ca(2)Y(2)Cu(5)O(10), we show that H(s) is solely determined by the IC and predict H(s)≈61 T for the latter. With H(s)≈55 T from magnetization data one reads out a weak IC for Li(2)CuO(2) close to that obtained from inelastic neutron scattering.

Spin gap in the zigzag spin-1/2 chain cuprate Sr(0.9)Ca(0.1)CuO(2).

We report a comparative study of (63)Cu nuclear magnetic resonance spin lattice relaxation rates T(1)(-1) on undoped SrCuO(2) and Ca-doped Sr(0.9)Ca(0.1)CuO(2) spin chain compounds. A temperature independent T(1)(-1) is observed for SrCuO(2) as expected for an S=1/2 Heisenberg chain. Surprisingly, we observe an exponential decrease of T(1)(-1) for T<90 K in the Ca-doped sample evidencing the opening of a spin gap. The data analysis within the J(1)-J(2) Heisenberg model employing density-matrix renormalization group calculations suggests an impurity driven small alternation of the J(2)-exchange coupling as a possible cause of the spin gap.

Online monitoring of cellular metabolism in the MCF-7 carcinoma cell line treated with phytoestrogen extracts.

BACKGROUND: Phytoestrogens are naturally occurring, plant-derived, nonsteroidal phytochemicals with anticarcinogenic potential. The aim of this study was to isolate phytoestrogens from the flax root of Linum usitatissimum and to test their effect on cellular metabolism in the human mammalian carcinoma cell line MCF-7 using the Bionas 2500 analysis system. MATERIALS AND METHODS: Metabolically relevant parameters such as acidification, oxygen consumption and cell adhesion were registered continuously over 8 and 24 hours on six sensor chips in parallel at different concentrations of flax root extracts. RESULTS: The extracts from flax roots of L. usitatissimum reduced extracellular acidification, respiration and adhesion in a concentration-dependent manner. CONCLUSION: The Bionas 2500 analysis system allows multiparametric online monitoring of cellular processes and can be used to detect the mode of action of anticarcinogenic compounds in cellular metabolism.

Spiral correlations in frustrated one-dimensional spin-1/2 Heisenberg J1-J2-J3 ferromagnets.

We use the coupled cluster method for infinite chains complemented by exact diagonalization of finite periodic chains to discuss the influence of a third-neighbor exchange J(3) on the ground state of the spin-½ Heisenberg chain with ferromagnetic nearest-neighbor interaction J(1) and frustrating antiferromagnetic next-nearest-neighbor interaction J(2). A third-neighbor exchange J(3) might be relevant to describe the magnetic properties of the quasi-one-dimensional edge-shared cuprates, such as LiVCuO(4) or LiCu(2)O(2). In particular, we calculate the critical point J(2)(c) as a function of J(3), where the ferromagnetic ground state gives way for a ground state with incommensurate spiral correlations. For antiferromagnetic J(3) the ferro-spiral transition is always continuous and the critical values J(2)(c) of the classical and the quantum model coincide. On the other hand, for ferromagnetic J3 is < or approximately equal to -(0.01...0.02)|J1|. the critical value J(2)(c) of the quantum model is smaller than that of the classical model. Moreover, the transition becomes discontinuous, i.e. the model exhibits a quantum tricritical point. We also calculate the height of the jump of the spiral pitch angle at the discontinuous ferro-spiral transition.

High-field pauli-limiting behavior and strongly enhanced upper critical magnetic fields near the transition temperature of an arsenic-deficient LaO0.9F0.1FeAs1-delta superconductor.

We report upper critical field Bc2(T) data for disordered (arsenic-deficient) LaO0.9F0.1FeAs1-delta in a wide temperature and magnetic field range up to 47 T. Because of the large linear slope of Bc2 approximately -5.4 to -6.6 T/K near Tc approximately 28.5 K, the T dependence of the in-plane Bc2(T) shows a flattening near 23 K above 30 T which points to Pauli-limited behavior with Bc2(0) approximately 63-68 T. Our results are discussed in terms of disorder effects within [corrected] unconventional superconducting pairings.

Optical study of LaO0.9F0.1FeAs: evidence for a weakly coupled superconducting state.

We have studied the reflectance of the recently discovered superconductor LaO0.9F0.1FeAs in a wide energy range from the far infrared to the visible regime. We report on the observation of infrared active phonons, the plasma edge, and possible interband transitions. On the basis of this data and the reported in-plane penetration depth lambda{L}(0)=254 nm [H. Luetkens, Phys. Rev. Lett. 101, 097009 (2008)] a disorder sensitive relatively small value of the total electron-boson coupling constant lambda{tot}=lambda{e-ph}+lambda{e-sp} approximately 0.6+/-0.35 can be estimated adopting an effective single-band picture.

Commensurate spin density wave in LaFeAsO: a local probe study.

We present a detailed study on the magnetic order in the undoped mother compound LaFeAsO of the recently discovered Fe-based superconductor LaFeAsO1-xFx. In particular, we present local probe measurements of the magnetic properties of LaFeAsO by means of 57Fe Mössbauer spectroscopy and muon-spin relaxation in zero external field along with magnetization and resistivity studies. These experiments prove a commensurate static magnetic order with a strongly reduced ordered moment of 0.25(5)muB at the iron site below T(N)=138 K, well separated from a structural phase transition at T(S)=156 K. The temperature dependence of the sublattice magnetization is determined and compared to theory. Using a four-band spin density wave model both, the size of the order parameter and the quick saturation below T(N) are reproduced.

Anisotropic multiband many-body interactions in LuNi2B2C.

We present a comprehensive de Haas-van Alphen study on the nonmagnetic borocarbide superconductor LuNi2B2C. The analysis of the angular-dependent effective masses for different bands in combination with full-potential density functional calculations allowed us to determine the mass-enhancement factors, lambda, for the different electronic bands and their wave-vector dependences. Our data clearly show the anisotropic multiband character of the superconductivity in LuNi2B2C.

Online monitoring of BALB/3T3 metabolism and adhesion with multiparametric chip-based system.

A multiparametric chip-based system was employed to measure cell adhesion, metabolism, and response to metal compounds previously classified as cytotoxic in immortalized mouse fibroblasts (BALB/3T3 cell line). The system measures in parallel, online, and in label-free conditions the extracellular acidification rates (with pH-sensitive field effect transistors [ISFETs]), the cellular oxygen consumption (with amperometric electrode structures [Clark-type sensors]), and cell adhesion (with impedimetric interdigitated electrode structures [IDESs]). The experimental protocol was optimized to monitor metabolism and adhesion of the BALB/3T3 cell line. A total of 70,000 cells and a bicarbonate buffer-free running low-glucose Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal clone serum III and 1mM Hepes were selected to maintain cells in good conditions on the chip during the measurements performed under perfusion conditions. Cells were exposed to sodium arsenite, cadmium chloride, and cis-platinum at concentrations ranging from 1 to 100 microM. The kinetics of cell response to these compounds was analyzed and suggests that the Clark-type sensors can be more sensitive than IDESs and ISFETs in detecting the presence of high chemical concentration when short exposure times (i.e., 2h) are considered. The cytotoxicity data obtained from the online measurements of acidification, respiration, and adhesion at 24h compare well, in terms of half-inhibition concentration values (IC(50)), with the ones obtained using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and colony-forming efficiency (CFE) assay. The results show a good sensitivity of the system combined with the advantages of the online and label-free detection methods that allow following cell status before, during, and after the treatment in the same experiment.

Frustrated cuprate route from antiferromagnetic to ferromagnetic spin-1/2 Heisenberg chains: Li2ZrCuO4 as a missing link near the quantum critical point.

From thermodynamics, local spin density approximation+Hubbard U studies and exact diagonalizations of a five-band Hubbard model on CuO2 stripes we find that Li2ZrCuO4 (Li2CuZrO4 in traditional notation) is close to a ferromagnetic critical point. Analyzing its susceptibility chi(T) and specific heat cp(T,H) within a Heisenberg model, we show that the ratio of the 2nd to the 1st neighbor exchange integrals alpha=-J2/J1 approximately 0.3 is close to the critical value alphac=1/4. Comparing with related chain cuprates we explain the rather strong field dependence of cp, the monotonic downshift of the peak of chi(T), and its increase for alpha-->alphac+0.

Physiology and pathophysiology of the 5-HT3 receptor.

The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.