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Testing and typing of eicosanoid-patterns

100%
Schafer D.
Journal of Physiology and Pharmacology. Supplement
|
2006
|
tom 57
|
nr 12
47-64
Eicosanoids are pleiotrope mediators with essential function in most biological processes. The network of inter- and intracellular signalling requires coordinated cellular information processing. The cross-talk is characterised by complex non-linear responses to combinations of different stimuli and cells, but little is known about the density of these interactions. Here I have analysed eicosanoid interactions carried out by functional eicosanoid testing and typing (FET) in leucocytes from healthy subjects and patients suffering from inflammatory diseases. The known eicosanoid pattern scoring was extended to metabolically linked prostaglandin E2 and peptido-leukotrienes pathways, both alone and in all pair wise combinations, for basal, maximal synthesis capacity, acetylsalicylic acid, and neuropeptide modification. Eicosanoids fluctuated over twenty minutes context-dependent dynamically, demanding further data integration. The integration suggested that many stimuli converge for quantitative discrimination applying a total eicosanoid pattern score (TEP). Varying cellular activities affect FET and thereby TEP. The non-additive metabolic interactions were consistent with known mechanisms of metabolic pathway cross-talk. FET-based modelling of eicosanoid circuits most suitably reflects the fundamental impact of eicosanoids in maintaining cellular integrity of organ and body function. This might improve our present understanding of complex cellular eicosanoid interactions of inflammatory diseases and might be applied for diagnostic considerations.
2
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Functional eicosanoid test and typing [FET] of peripheral blood cells in eicosanoid related diseases

63%
Schafer D., Baenkler H. W.
Journal of Physiology and Pharmacology. Supplement
|
2005
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tom 56
|
nr 5
103-118
Monitoring of eicosanoid synthesis in peripheral blood cells has significant potential for improving the diagnosis and therapy of many human diseases. The quantitative relation between concentrations of prostaglandins and leukotrienes is central to the physiologic function of the eicosanoid network. Here we show that this regulation, which we call the functional eicosanoid typing (FET), fluctuates dynamically in individual living blood cells from patients, thereby limiting the accuracy with which concentration circuits of eicosanoids can transfer metabolic information. Using living cells in functional cell testing, we characterised the eicosanoid pattern score (EPS). A novel technique based on binomial errors on lipid mediator partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that eicosanoid production rates fluctuate over a time scale of about twenty minutes, while intrinsic noise decays rapidly. Thus, biochemical eicosanoid parameters, noise, and slowly varying cellular states together determine the effective FET. These results can form a basis for quantitative modelling of natural eicosanoid circuits in diagnosis of eicosanoid related diseases and design of synthetic ones for the prediction other diseases.
3

Abnormal eicosanoid-pattern of peripheral white-blood-cells in gastro-intestinal cancer

63%
Baenkler H. W., Schafer D.
Journal of Physiology and Pharmacology. Supplement
|
2005
|
tom 56
|
nr 5
119-128
COX-inhibitors promote nasal polyps or bronchial asthma in individuals susceptible to an alteration of the pattern of the eicosanoids, especially leukotrienes and prostaglandins. This is associated with an abnormal release of eicosanoids from white blood cells. Since COX-inhibitors also protect from colorectal cancer an analogous association may be suggested. The study was performed to detect abnormal patterns of eicosanoids in white blood cells of patients with intestinal cancer compared to healthy controls. Seventy patients with intestinal cancer (stomach = 5; colon = 25; sigma = 18; rectum = 22) were compared to 62 healthy controls. Blood leukocytes from patients in complete long-lasting remission were incubated with diluent, arachidonic acid or acetylsalicylic acid. The synthesis of prostaglandin E2 and peptido-leukotrienes was quantified using competitive enzyme-immuno-assays and calculated for individual eicosanoid patterns. The mean basal and arachidonic- or acetylsalicylic acid-modulated PGE2 synthesis in patients was significantly higher than in controls (4.8-fold, 9.4-fold, 3.7-fold, respectively) whereas pLT was generally less elevated. We conclude that the eicosanoid-pattern of white-blood-cells from patients with intestinal cancer differs significantly from that in healthy individuals. This abnormal cellular metabolism may contribute to the manifestation of cancer and help to detect individuals at risk.
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