LBN, SE 175, and latanoprost caused relaxation of ET-1-contracted HTMCs. The effect on HTMC relaxation observed with LBN was significantly greater in magnitude than that observed with latanoprost or SE 175. Data indicate that the NO-donating moiety of LBN mediates HTMC relaxation through activation of the cGMP signaling pathway and a subsequent reduction in MLC-2 phosphorylation. These findings suggest that increased conventional outflow facility may mediate the additional IOP-lowering effects of LBN over that of latanoprost observed in in vivo studies.
Episodes of hospitalization for heart failure patients are frequent and are often accompanied by fluid accumulations. The change of the body impedance, measured by bioimpendace spectroscopy, is an indicator of the water content. The hypothesis was that it is possible to detect edema from the impedance data. First, a finite integration technique was applied to test the feasibility and allowed a theoretical analysis of current flows through the body. Based on the results of the simulations, a clinical study was designed and conducted. The segmental impedances of 25 patients suffering from heart failure were monitored over their recompensation process. The mean age of the patients was 73.8 and their mean body mass index was 28.6. From these raw data the model parameters from the Cole model were deduced by an automatic fitting algorithm. These model data were used to classify the edema status of the patient. The baseline values of the regression lines of the extra- and intracellular resistance from the transthoracic measurement and the baseline value of the regression line of the extracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of peripheral edema. The rate of change of the imaginary impedance at the characteristic frequency and the mean intracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of pulmonary edema. To classify the data, two decision trees were considered: One should detect pulmonary edema (n(pulmonary) = 13, n(none) = 12) and the other peripheral edema (n(peripheral) = 12, n(none) = 13). Peripheral edema could be detected with a sensitivity of 100% and a specificity of 90%. The detection of pulmonary edema showed a sensitivity of 92.31% and a specificity of 100%. The leave-one-out cross-validation-error for the peripheral edema detection was 12% and 8% for the detection of pulmonary edema. This enables the application of BIS as an early warning system for cardiac decompensation with the potential to optimize patient care.
Electrical impedance tomography (EIT) provides global and regional information about ventilation by means of relative changes in electrical impedance measured with electrodes placed around the thorax. In combination with lung function tests, e.g. spirometry and body plethysmography, regional information about lung ventilation can be achieved. Impedance changes strictly correlate with lung volume during tidal breathing and mechanical ventilation. Initial studies presumed a correlation also during forced expiration maneuvers. To quantify the validity of this correlation in extreme lung volume changes during forced breathing, a measurement system was set up and applied on seven lung-healthy volunteers. Simultaneous measurements of changes in lung volume using EIT imaging and pneumotachography were obtained with different breathing patterns. Data was divided into a synchronizing phase (spontaneous breathing) and a test phase (maximum effort breathing and forced maneuvers). The EIT impedance changes correlate strictly with spirometric data during slow breathing with increasing and maximum effort ([Formula: see text]) and during forced expiration maneuvers ([Formula: see text]). Strong correlations in spirometric volume parameters [Formula: see text] ([Formula: see text]), [Formula: see text]/FVC ([Formula: see text]), and flow parameters PEF, [Formula: see text], [Formula: see text], [Formula: see text] ([Formula: see text]) were observed. According to the linearity during forced expiration maneuvers, EIT can be used during pulmonary function testing in combination with spirometry for visualisation of regional lung ventilation.
Background: Mapracorat is a drug candidate for ocular and skin inflammatory diseases. Its anti-inflammatory mechanism is not fully understood. Results: Mapracorat augments MKP-1 expression, accelerates p38 deactivation, and inhibits the production of pro-inflammatory mediators. Conclusion: Mapracorat exerts its anti-inflammatory effects, at least in part, by augmenting MKP-1. Significance: This study highlights the therapeutic potential of augmenting the endogenous anti-inflammatory regulators.
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