Warm afterglow from the Toarcian Oceanic Anoxic Event drives the success of deep-adapted brachiopods.

Many aspects of the supposed hyperthermal Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, c. 182 Ma) are well understood but a lack of robust palaeotemperature data severely limits reconstruction of the processes that drove the T-OAE and associated environmental and biotic changes. New oxygen isotope data from calcite shells of the benthic fauna suggest that bottom water temperatures in the western Tethys were elevated by c. 3.5 °C through the entire T-OAE. Modelling supports the idea that widespread marine anoxia was induced by a greenhouse-driven weathering pulse, and is compatible with the OAE duration being extended by limitation of the global silicate weathering flux. In the western Tethys Ocean, the later part of the T-OAE is characterized by abundant occurrences of the brachiopod Soaresirhynchia, which exhibits characteristics of slow-growing, deep sea brachiopods. The unlikely success of Soaresirhynchia in a hyperthermal event is attributed here to low metabolic rate, which put it at an advantage over other species from shallow epicontinental environments with higher metabolic demand.

High intensity proton injector for facility of antiproton and ion research.

The high current ion source with the low energy beam transport (LEBT) will serve as injector into the proton LINAC to provide primary proton beam for the production of antiprotons. The pulsed ion source developed and built in CEA/Saclay operates with a frequency of 2.45 GHz based on ECR plasma production with two coils with 87.5 mT magnetic field necessary for the electron cyclotron resonance. The compact LEBT consists of two solenoids with a maximum magnetic field of 500 mT including two integrated magnetic steerers to adjust the horizontal and vertical beam positions. The total length of the compact LEBT is 2.3 m and was made as short as possible to reduced emittance growth along the beam line. To measure ion beam intensity behind the pentode extraction system, between solenoids and at the end of the beam line, two current transformers and a Faraday cup are installed. To get information about the beam quality and position, the diagnostic chamber with different equipment will be installed between the two solenoids. This article reports the current status of the proton injector for the facility of antiproton and ion research.

Investigation of ion beam space charge compensation with a 4-grid analyzer.

Experiments to investigate the space charge compensation of pulsed high-current heavy ion beams are performed at the GSI ion source text benches with a 4-grid analyzer provided by CEA/Saclay. The technical design of the 4-grid analyzer is revised to verify its functionality for measurements at pulsed high-current heavy ion beams. The experimental investigation of space charge compensation processes is needed to increase the performance and quality of current and future accelerator facilities. Measurements are performed directly downstream a triode extraction system mounted to a multi-cusp ion source at a high-current test bench as well as downstream the post-acceleration system of the high-current test injector (HOSTI) with ion energies up to 120 keV/u for helium and argon. At HOSTI, a cold or hot reflex discharge ion source is used to change the conditions for the measurements. The measurements were performed with helium, argon, and xenon and are presented. Results from measurements with single aperture extraction systems are shown.

The proton injector for the accelerator facility of antiproton and ion research (FAIR).

The new international accelerator facility for antiproton and ion research (FAIR) at GSI in Darmstadt, Germany, is one of the largest research projects worldwide and will provide an antiproton production rate of 7 × 10(10) cooled pbars per hour. This is equivalent to a primary proton beam current of 2 × 10(16) protons per hour. For this request a high intensity proton linac (p-linac) will be built with an operating rf-frequency of 325 MHz to accelerate a 35 mA proton beam at 70 MeV, using conducting crossed-bar H-cavities. The repetition rate is 4 Hz with beam pulse length of 36 µs. The microwave ion source and low energy beam transport developed within a joint French-German collaboration GSI/CEA-SACLAY will serve as an injector of the compact proton linac. The 2.45 GHz ion source allows high brightness ion beams at an energy of 95 keV and will deliver a proton beam current of 100 mA at the entrance of the radio frequency quadrupole (RFQ) within an acceptance of 0.3π mm mrad (norm., rms).

Ischemic and inflammatory lung impairment by extracorporeal circulation: effect of PARP-inhibition by INO1001.

OBJECTIVE: Among the complications after cardiac surgery the development of postoperative pulmonary distress is a serious problem. Typically, the patients leave the operating theatre with good blood gas values and O(2)-saturation, but develop their respiratory problems within the next hours/days. We investigated whether extracorporeal circulation may induce biochemical and histological changes in the lungs which may help to explain this development. METHODS: Piglets (6-10 kg) were anaesthetized using isoflurane and underwent extracorporeal circulation (ECC) with hypothermic (25-28 degrees C) cardioplegic arrest for 90 min followed by 3h reperfusion. An additional group received a poly(ADP-ribose) polymerase (PARP)-Inhibitor, INO1001. Cardiopulmonary monitoring was performed during the whole procedure. Finally, lungs were explanted and investigated by histomorphometry and immunohistology for heat shock protein HSP70 (indicator for cellular damage) and TNFalpha in comparison to normal piglets without ECC. RESULTS: Histologically we found significant swelling of the type I alveocytes (thickness increased from 2.4 to 3.2 microm), interstitial oedema, intra-alveolar erythrocyte (4.8 versus 0.4 erythrocytes/alveole) and granulocyte accumulation and fibrinous exudates. There was a significant up-regulation of TNFalpha and of the cellular repair enzyme HSP70, while in control piglets only minimal levels were observed. INO1001 significantly reduced ECC-induced elevation in TNFalpha and in HSP70. Despite the dramatic changes after heart-lung-machine (HLM), blood gases and gas transport were almost not affected at that time. CONCLUSIONS: ECC can lead to early significant histological and histochemical changes which have similarities with a beginning early stage shock lung, although - at 3h reperfusion - gas transport is still sufficient. INO1001 can partially antagonize these changes.

Ultrastructural findings in porcine hearts after extracorporeal long-term preservation with a modified Langendorff perfusion system.

Preserved ultrastructure is an important precondition for functional regeneration after heart transplantation. We investigated the effectiveness of a newly developed modified Langendorff system in extracorporeal heart perfusion. (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts were connected to a modified Langendorff system, and perfused with leucocyte depleted autologous blood. (Experiment II) The untreated hearts of three healthy pigs served as controls. Forty-seven myocardial biopsies at different timepoints (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy. Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling, mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema. After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema and haemorrhages appeared. Untreated hearts (II) showed severely damaged mitochondria and nuclei after 30 min while the myofibrillar structure remained unaffected until 4 h later. This is a promising model for extracorporeal heart perfusion. However, ultrastructural findings indicated that some necessary modifications to prevent cellular damages during reperfusion were needed.

Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy.

Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine. Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p<0.05, n=6 each) but not in the FVB/N strain. These results correlate differential expression of excitatory class mGluR I and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability.

Epicardial treatment of atrial fibrillation using cryoablation in an acute off-pump sheep model.

BACKGROUND: The purpose of this study was to test the feasibility and effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare Inc., Irvine, California, USA) for linear epicardial treatment of atrial fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing electrodes positioned at the left atrial appendage (LAA), the pulmonary veins (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8 sheep. Circular epicardial ablations were performed with online temperature measurement in the ascending aorta and in the esophagus. The sheep were sacrificed two hours after ablation procedure, and heart, lungs, and esophagus were retrieved for histological examination. Out of all 8 sheep, histo-pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed electrical isolation. No significant changes in temperature in the descending aorta and the esophagus were observed. There was evidence of extensive transmural alteration including vascular lesions, myocardial degeneration and necrosis as well as epi- and endocardial necrosis in the left atria in three of 8 cases, in the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5 of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7 of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker tissues like LAA and RAA due to the rewarming of the current blood flow. However, thin tissues like VCC and PV can be isolated. Further chronic studies are necessary to evaluate the potential for regeneration of adjacent structures.

Influence of propiverine on hepatic microsomal cytochrome p450 enzymes in male rats.

The bladder spasmolytics propiverine was shown to induce hepatic cytochrome P450 (P450) and aminopyrine and aniline oxidation in rats. To characterize the type of enzyme induction and its dose dependence, activities of seven hepatic microsomal P450-dependent monooxygenases were measured in 72 male LEW1A albino rats (body weight 236-295 g) after oral treatment with 0.5, 2, 6, and 60 mg/kg of propiverine hydrochloride for 5 days and compared with the effects of 40 mg/kg beta-naphthoflavone, 10 mg/kg phenobarbital, and 20 mg/kg dexamethasone (each group, n = 8). CYP2B expression was measured by Western blotting. Furthermore, the inhibitory potency of propiverine on P450 enzymes was evaluated in competition assays with three most specific monooxygenases. Results show that Propiverine induced several monooxygenases and CYP2B expression dose dependently. The effects were well comparable with a phenobarbital-type inducer with 60 mg/kg being equipotent to 10 mg/kg phenobarbital. Furthermore, propiverine in low concentrations inhibited pentylresorufin O-dealkylase (for CYP2B) in vitro. In conclusion, propiverine is a phenobarbital-type inducer on hepatic P450 enzymes in rats in doses about 100-times above the therapeutic doses in man.

A new intracardiac microaxial pump: first results of a multicenter study.

As coronary artery bypass grafting (CABG) surgery in the beating heart technique is progressing, new devices have been developed to overcome hemodynamic instabilities while tilting the heart for exposure of back wall vessels. A new device for in heart biventricular intracorporeal circulation was applied in 42 patients undergoing CABG surgery (Group 1). The control group consisted of 38 patients operated on using a conventional cardiopulmonary bypass setup (Group 2). The study protocol of the prospective, randomized multicenter study was approved by the local ethics committees. Patients were included following inclusion criteria and patient informed consent. Mean age, procedure time, mean arterial pressure (MAP), and hemolysis by means of plasma free hemoglobin (fHb) were assessed preoperatively, perioperatively, on postoperative Days 1 to 3, at discharge, and at a 3 month follow-up. The mean age was 62.1 (range 59-74) years (Group 1), 62.7 (range 48-72) years (Group 2); procedure time was 112 min +/- 31.9 min (Group 1), 137.4 min +/- 36.2 min (Group 2); and 2.3 +/- 0.6 (Group 1), 2.2 +/- 0.7 (Group 2), vessels were revascularized. The flow on pump was 3.7 (2.5/4.4) L/min (Group 1), 4.9 (3.6/6.2) L/min (Group 2) which resulted in a MAP of 69.8 (4.0/143) mm Hg (Group 1), 58.3 (5.3/94) mm Hg while assessing the vessels of the back wall. Hemolysis defined by fHB was lower than 20 mg/dl at all times pre- and postoperatively. Intraoperative maximum values were up to 100 mg/dl in 4 patients (2 in Group 1 and 2 in Group 2). Body mass index was 26.4 +/- 2.6 (Group 1), 27.9 +/- 3.2. New York Heart Association Class was II to III in both groups. There were no pump related life threatening or severe adverse events. Beating heart procedures with ICC can be reliably and safely achieved. As the device is easy to use, it may deserve a more widespread use in the future.