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Dynamic linearity ofVO2 responses during aerobic exercise

Summary The multifrequent pseudorandom binary sequence (PRBS) technique is a useful tool for studying oxygen uptake ( ) kinetics within the aerobic range. However, the validity of this multifrequent test may be limited by nonlinearities generated by the circulatory and pulmonary system. To check for such nonlinear effects, we compared the frequency responses computed from two PRBS protocols with the results of pure sinusoidal frequencies varying in amplitude and mean values (periods between 50 s and 450 s). According to our results the frequency response does not seem to depend on the type of testing — PRBS or sine — or the changes within each test, i.e. mean power and power amplitude of the sine tests and the switching frequency of the PRBS. In the range of higher frequencies small differences between the test conditions may have been obscured by the greater scatter of dynamic responses. It was concluded that the frequency response was quasi-linear for periods down to at least 100 s. However, even in this range nonlinearities can be provoked by rest-exercise transitions, by a varying contribution of lactate or by an insufficient noise reduction.     

Intraoperative Analgesiesteuerung: Analgesie Nociception Index (ANI) vs. „standard care“ bei Hysterektomien unter Sevoflurannarkose

Die Anaesthesiologie - Während zu klinischer Überwachung und Kontrolle von Hypnose und Muskelrelaxation validierte Methoden im Anästhesiealltag existieren, basiert die...     

Tropisetron via α7 nicotinic acetylcholine receptor suppresses tumor necrosis factor‐α‐mediated cell responses of human keratinocytes

Tropisetron is a serotonin receptor (5‐HT‐R)‐modulating agent and approved as an antiemetic for patients undergoing chemotherapy. In the gut, it acts via specific serotonin receptors, 5‐HT₃‐R, to elicit its beneficial effects against nausea. We investigated whether tropisetron can affect inflammatory cell responses of human primary epidermal keratinocytes (NHK) which are key cells in the regulation of skin homoeostasis. Tropisetron significantly and dose‐dependently suppressed tumor necrosis factor (TNF)‐α‐mediated mRNA expression and protein secretion of interleukin (IL)‐6 and IL‐8 in these cells. This effect of tropisetron was independent of p65/NF‐κB as shown by various NF‐κB signal transduction read‐outs. Importantly, the anti‐inflammatory tropisetron effect on NHK was neither mediated by 5‐HT₃‐R nor 5‐HT₄‐R since these receptors were absent in NHK. In contrast, NHK expressed α7 nicotinic acetylcholine receptors (α7nAchR) which previously were found to bind tropisetron. The α7nAchR antagonist α‐bungarotoxin neutralized, whereas AR‐R17779, a specific α7nAchR agonist, mimicked the suppressive effect of tropisetron on TNF‐α‐mediated IL‐6 and IL‐8 expression in NHK. Our findings suggest that tropisetron and probably other α7nAchR‐activating agents could be useful for the future therapy of inflammatory skin diseases.     

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, search for factors regulating this pathway are strongly desired. Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. Our in vitro assessment indicates an oncostatic capacity of melatonin in time‐dependent manner (24, 48, 72 hours) in highly pigmented MNT‐1 melanoma cells. The similar pattern of regulation regarding cell viability was observed in amelanotic Sk‐Mel‐28 cells. Subsequently, MNT‐1 cells were tested for the first time for evaluation of melanin/melatonin interaction. Thus primary, electron paramagnetic resonance (EPR) spectroscopy demonstrated that melatonin reduced melanin content. Artificially induced disturbances of melanogenesis by selected inhibitors (N‐phenylthiourea or kojic acid) were slightly antagonized by melatonin. Additionally, analysis using transmission electron microscopy has shown that melatonin, particularly at higher dose of 10^?3 mol/L, triggered the appearance of premelanosomes (stage I‐II of melanosome) and MNT‐1 cells synthesize de novo endogenous melatonin shown by LC‐MS. In conclusion, these studies show a melanogenic‐like function of melatonin suggesting it as an advantageous agent for treatment of pigmentary disorders.