Online monitoring of cell metabolism for studying pharmacodynamic effects

To characterize modes of action of substances and their cytotoxic effects Bionas GmbH has developed a new screening system to allow the continuous recording of how an active substance can act (Bionas 2500 analyzing system). In the pharmaceutical industry it is important to acquire as much information as possible about the metabolic effects of an active substance. Most classical pre-clinical studies are very expensive and time-consuming. Often they are so-called end-point tests which require many individual tests before approximate statements can be made about how an effect takes its course. With the Bionas 2500 analyzing system metabolically relevant data including oxygen consumption, acidification rate and the adhesion (cell impedance) of cells can be measured in parallel, online and label-free. Using e.g. ion-sensitive field effect-transistors (ISFET) and electrode structures it is possible to observe metabolic parameters non-invasively and continuously over longer periods of time. The system has already been established for several cell models, cell lines as well as primary cells. It also offers the advantage that regenerative effects can be observed during the same test run.     

Effect in cat locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered paCO2

In pentobarbital-anesthetized cats, over arterial p_aCO₂ values of 20–60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflected curves with slopes significantly greater than zero. To examine the role of the locus coeruleus (LC) in these responses, bilateral stereotactic thermo-coagulation lesions of the LC were made. The effect of lesions confirmed to involve the LC bilaterally (n= 10), were compared with the effects of misdirected lesions placed in the cerebellum abd lateral to the LC (n= 10) and sham lesions (n= 10). Ted days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and p_aCO₂ response curves were determined for CBF and CO prior to and following intravenous administration of propranolol (1 mg/kg, i.v.). The results obtained with the sham-operated animals and the animals with lesions outside of the LC were indistinguishable. Bilateral LC lesions had no significant effect on normocapnic CBF as compared to control animals. They did, however, significantly reduce the slope of the CBF p_aCO₂ response curve. Propranolol produced a significant reduction in CBF in lesioned and non-lesioned animals measured at all levels of pCO₂ and did not alter the slope of the pCO₂ response curve for any group as compared to predrug values. Bilateral lesions of the LC did not significantly alter either normacapnic CO or the slope of the CO-p_aCO₂ relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close indicate a correlation between the ability of the lesion to reduce norepinephrine content and produce the observed physiological effects. The results of these experiments suggest that the hypercapnic response of CBF, but not CO to arterial p_aCO₂ is modulated by systems which traverse the dorsal brainstem. The role of the locus coeruleus-catecholamine cell bodies in this effect, however, must be considered speculative until further transmitter-selective interventions are carried out.     

Highly parallel volumetric imaging with a 32-element RF coil array.

The improvement of MRI speed with parallel acquisition is ultimately an SNR-limited process. To offset acquisition- and reconstruction-related SNR losses, practical parallel imaging at high accelerations should include the use of a many-element array with a high intrinsic signal-to-noise ratio (SNR) and spatial-encoding capability, and an advantageous imaging paradigm. We present a 32-element receive-coil array and a volumetric paradigm that address the SNR challenge at high accelerations by maximally exploiting multidimensional acceleration in conjunction with noise averaging. Geometric details beyond an initial design concept for the array were determined with the guidance of simulations. Imaging with the support of 32-channel data acquisition systems produced in vivo results with up to 16-fold acceleration, including images from rapid abdominal and MRA studies.     

Comparison of three multichannel transmit/receive radiofrequency coil configurations for anatomic and functional cardiac MRI at 7.0T: implications for clinical imaging

Objectives

To implement, examine, and compare three multichannel transmit/receive coil configurations for cardiovascular MR (CMR) at 7T.

Methods

Three radiofrequency transmit-receive (TX/RX) coils with 4-, 8-, and 16-coil elements were used. Ten healthy volunteers (seven males, age 28?±?4?years) underwent CMR at 7T. For all three RX/TX coils, 2D CINE FLASH images of the heart were acquired. Cardiac chamber quantification, signal-to-noise ratio (SNR) analysis, parallel imaging performance assessment, and image quality scoring were performed.

Results

Mean total examination time was 29?±?5?min. All images obtained with the 8- and 16-channel coils were diagnostic. No significant difference in ejection fraction (EF) (P?>?0.09) or left ventricular mass (LVM) (P?>?0.31) was observed between the coils. The 8- and 16-channel arrays yielded a higher mean SNR in the septum versus the 4-channel coil. The lowest geometry factors were found for the 16-channel coil (mean ± SD 2.3?±?0.5 for R?=?4). Image quality was rated significantly higher (P?Conclusions All three coil configurations are suitable for CMR at 7.0T under routine circumstances. A larger number of coil elements enhances image quality and parallel imaging performance but does not impact the accuracy of cardiac chamber quantification.

Key Points

? Cardiac chamber quantification using 7.0T magnetic resonance imaging is feasible. ? Examination times for cardiac chamber quantification at 7.0T match current clinical practice. ? Multichannel transceiver RF technology facilitates improved image quality and parallel imaging performance. ? Increasing the number of RF channels does not influence cardiac chamber quantification.     

The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.     

Infective endocarditis resulting from CardioSEAL closure of a patent foramen ovale.

Patent foramen ovale and atrial septal aneurysm are associated with an increased risk of cryptogenic stroke and recurrent thromboembolic events. Percutaneous closure is a therapeutic option to medical therapy and surgical closure. We present the first case of endocarditis associated with a CardioSEAL device closing a patent foramen ovale.