1,721,151 research outputs found
Nicht-invasive Bestimmung des Herzschlagvolumens mittels Impedanzkardiographie und Acetylenrückatmung in Abhängigkeit exogener Einflußfaktoren
No full textHypergravitationsinduzierte Effekte auf cGMP-Konzentration humaner Melanozyten und Melanomzellen
No full textEnvironmental signals such as an altered acceleration vector (micro- and hypergravity) may influence cell morphology, proliferation, response to growth factors, gene expression, and metabolism. Despite the growing interest in the regulation of signaling activities in normal and transformed cells under altered gravity conditions, little is known how normal human melanocytes and melanoma cells respond to such environmental factors. In human skin, melanocytes function as a pivotal protective barrier against UV irradiation and oxidative stress by generating the radical-scavenging pigment melanin. Moreover, as human skin is repeatedly exposed to mechanical stimuli, it has been found that human melanocytes may also sense mechanical forces such as mechanical pressure and cyclic stretch. As guanosine 3',5'-cyclic monophosphate (cGMP) is known to play an important signaling role in human melanocytes and different guanylyl cyclase isoforms are responsible for the cGMP synthesis in nonmetastatic and metastatic melanoma cells, the effects of hypergravity on the regulation of cGMP levels in normal human melanocytes and in melanoma cell lines with different metastatic potential have been investigated. Hypergravity stimulus was provided using horizontal centrifugal acceleration. The present study demonstrates that long-term exposure of cultured human melanocytes and nonmetastatic melanoma cells to hypergravity (up to 5g for 24 h) induced a decrease in intracellular and an increase in extracellular cGMP levels in the presence of isobutylmethylxanthine as a nonspecific inhibitor of the phosphodiesterase-mediated cyclic nucleotide hydrolysis. Such alterations were equally prominent despite the presence of trequinsin and zaprinast as inhibitors of cGMP-specific phosphodiesterases and of the cGMP transport by the multidrug resistance proteins MRP4 and MRP5. Importantly, expression and stimulation of soluble guanylyl cyclase isoform by a nitric oxide donor and of the membrane isoforms by natriuretic peptides were not changed by hypergravity in comparison to 1g controls. Thus, the hypergravity-induced alteration in cGMP levels was due to a stimulation of the cGMP export into the extracellular space. On the other hand, cyclic AMP efflux in normal human melanocytes and nonmetastatic melanoma cells was not altered, but production of cAMP appeared to be stimulated by centrifugal acceleration as is evident by the similar increase in intra- and extracellular cAMP levels, which was associated with enhanced melanin formation in pigmented human melanocytes. In contrast, metastatic melanoma cells were apparently insensitive to hypergravity. Taken together, the present results indicate that the environment created by centrifugal acceleration represents a new factor for regulating cyclic nucleotide levels in human melanocytes
Einfluss kurzzeitiger Immobilisation in 6 Kopftieflage auf die Kinetik des Muskelabbaus
No full textThe aim of this study was to analyse, if there are any changes in muscle turnover after a short term bed rest in a -6° head down tilt position. Simultaneously with the measurements of the marker of muscle mass and breakdown such as kreatinine, 3 Methylhistidine, urea, serum protein and serum amino acid concentrations, we also determined a calf circumference and above all maximum voluntary plantar flexion force as a marker of muscle size and function. Eight healthy, male test subjects participated in this study which was performed in a randomized crossover design. Each of the two study phases consisted of 2 dietary adaptation days (ambulatory) and 11 days (24 h/day) in the metabolic ward [Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany]. The metabolic ward days were divided into a 4-day ambulatory period, a 6-day intervention period: either bed rest [-6° headdown tilt (HDT)] or non-bed rest, and 1 recovery day. The same sequence was repeated after a four day break. During both 11-day periods in the ward, constant room temperature (24°C) and relative humidity (50%) were ensured. Both study phases were identical with respect to environmental conditions, study protocol, and diet. During the bed rest phase, subjects were kept in bed for 24 h and were not allowed to elevate their heads > 30° from horizontal. Horizontal movement was allowed. All activities, including showering and weighing, were carried out either in horizontal or in the 6° HDT position. During the non-bed rest phase, the subjects were allowed to walk around in the ward. The volunteers received a diet according to dietary reference intake values of German association of nutrition. To avoid any impact of nutrients other than the controlled foods, the menu as well as the meal frequency and the dietary energy intake was identical during both phases. The data of our short-term bed rest study in a crossover design show that unloading of weightbearing muscles does not lead to increased excretion of markers of muscle mass, like creatinine, or of muscle breakdown, like urea and 3-Me-His excretion. Together with the unchanged excretion of these parameters, neither serum protein concentration nor serum amino acid concentration increased. The weight loss of all test persons was due to the fluid shift and changed fluid balance caused by increased urin excretion at the beginning of the immobilisation phase. There was a significant decrease of the 3,98% in the size of the calf muscles in the intervention group in comparisson with the non-bed rest group. The maximum voluntary calf muscle force velocity also showed a significant decrease by 6,2%. These results prove that after a short immobilisation in -6°HDT a significant decrease in the function of the calf muscles appear without a corresponding biochemical correlation.Therefore we conclude that- a short term immobilisation by means of a 6 day bed rest in a head down tilt position do not inevitably lead to a significant rise in muscle protein breakdown, - any change in muscle mass during bed rest is therefore most likely associated with a decrease in skeletal muscle protein synthesis rather than in protein breakdown, - the changes in serum amino acid concentration can not be varified without the measurement of the protein synthesis flows,- in future studies tracer dilution techniques and a longer term immobilisation phases should be included to analyse additional dynamic changes in protein metabolism
Partieller Schlafentzug: Auswirkungen auf Schlafarchitektur, Schlafqualität und zirkadiane Rhythmik
No full textZirkadiane Rhythmik und Schlafqualität : Beeinflussung durch partiellen Schlafentzug im Vergleich zu Hypoxie und Alkohol als Referenzstressoren
No full textIndividuelle UV-Strahlenexposition ausgewählter Gruppen der Bevölkerung in Deutschland : Auswertung von Messkampagnen mit einem biologisch wichtenden UV-Personendosimeter unter besonderer Berücksichtigung des sich ändernden UV-Strahlenklimas
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Gastroenteropankreatische und endokrine Reaktionen auf Kinetosen bei 15 russischen Kosmonauten
No full textEinfluss von Hypergravitation auf den cGMP-Efflux in Stickstoffmonoxid-stimulierten humanen Melanozyten und Melanomzellen
No full textGravity alteration is known to affect cell proliferation, morphology, gene expression, and me-tabolism. To our knowledge, studies concerning the gravity influence on melanocyte physiol-ogy with respect to activation and cellular responses that are important for malignant trans-formation have been rarely reported. Since melanocytes are able to sense mechanical forces and transform them into biochemical signals it was assumed that these cells likewise respond to gravity alteration. We examined whether hypergravity (up to 5g for 24 h) modulates the efflux of the second messenger cGMP under conditions of stimulated cGMP-synthesis. Due to the differential expression of functional guanylyl cyclase (GC) isoforms in normal human melanocytes (NHM) and melanoma cell lines we used direct NO donors (NONOates) which differ in their kinetics of NO release as stimulators of sGC and ANP as a GC-A modulator. Our results demonstrate that long-term application of hypergravity (5g for 24 h) in the presence of DETA/NO induced a decrease in intracellular cGMP in NHMs and non-metastatic 1F6 melanoma cells compared to cGMP levels at 1g. The corresponding extracellular cGMP levels increased suggesting that hypergravity enhances the cGMP efflux. This efflux was re-duced in the presence of trequinsin as a selective phosphodiesterase 5 inhibitor and additionally a highly selective inhibitor of multidrug resistance protein 4/5, indicating that in melanocytes the hypergravity-stimulated cGMP efflux under PDE5 inhibition is most proba-bly mediated by endogenous anion transporters and/or selective cGMP transporters like MRP 4/5. Short-term application (5g up to 6 h) was not effective. Compared to the 1g-controls there existed no differences between intra- and extracellular cGMP-levels. These results indicate that short-term centrifugation did not affect cGMP efflux in melanocytic cells. Interestingly, highly metastatic melanoma cells were apparently insensitive to a 24 hour centrifugation in the presence of ANP. These cells that do not express the NO-sensitive GC isoforms, showed no alteration in intra- and extracellular cGMP concentrations. Application of hypergravity did not alter the cAMP efflux in melanocytic cells, but the production of cAMP appeared to be stimulated by centrifugal acceleration. In summary, the presented in vitro experiments demonstrate that long-term exposure to hypergravity increases the cGMP efflux in NO-stimulated NHMs and non-metastatic melanoma cells, whereas highly metastatic melanoma cells are not sensitive. Thus an altered acceleration vector may induce cGMP-dependent signalling events in NO-stimulated human melanocytic cells
Differente Expression der Multidrug-Resistenz-Proteine 4/5 in nicht und stark metastasierenden Melanomzellen unter Hypergravitationsbedingungen
No full textMultidrug resistance proteins (MRPs) are transmembrane proteins with the potential to export a wide range of substances in the extracellular space preventing cells from toxification. MRP4 and 5, on which this investigation is focused, particularly mediate nucleoside-analogue export, i.e. guanosine 3´, 5´-cyclic monophosphate (cGMP) and conjugated nucleosides. cGMP plays an important signaling role in melanocytic physiology, especially in the UV-B induced melanogenesis. Previous studies could show that long-term exposure to mechanical stress in terms of hypergravity leads to an increased cGMP efflux in non-metastatic melanoma cell lines, whereas the highly metastatic phenotype appeared to be insensitive. Biochemical analysis let assume that overexpressed MRP4, 5 and 8 could be responsible for these effects. Based on these results the aim of the present study was to investigate the effects of hypergravity (5xg for 24 h) on mRNA and protein levels of MRP4, 5, and/or 8. The data show that the mRNA as well as the protein levels of MRP4 and MRP5 were about 1.4-fold higher in non-metastatic melanoma cells exposed to hypergravity in comparison to 1xg controls. In contrary, the expressions of MRP4 and 5 in highly metastatic cells remained unaffected. For MRP8 we basically measured low mRNA and protein expression levels in all investigated cell lines independent of gravity alterations. Our studies indicate that the previously found elevated cGMP export in hypergravity could be a consequence of an upregulated expression of MRP4 and MRP5 in non-metastatic melanoma cells, whereas a MRP8-driven export can be excluded. Furthermore, the elevated cGMP efflux and MRP expressions seems to be a part of an adaptation process for non-metastatic melanoma cells to hypergravity conditions. Since enhanced MRP expression is responsible for a decreased drug uptake in cells, a gravity-modified MRP expression on long-term space flights can lead to an altered drug tolerance and efficiency in astronauts
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