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61.
62.
MDR1 P-glycoprotein transports endogenous opioid peptides 总被引:3,自引:0,他引:3
MDR1 P-glycoprotein is generally regarded as an efflux pump for amphipathic toxic compounds. The question remains, however, whether certain endogenous compounds are also substrates for this transporter. Certain peptides have been shown to interact with MDR1 Pgp as well and we have therefore investigated whether endogenous bioactive peptides are substrates. We demonstrate here that the synthetic μ-opioid peptide DAMGO is a good substrate for MDR1 Pgp. In view of its low interaction with the membrane it is an attractive ligand for measurement of MDR1 Pgp-mediated transport activity in membrane vesicles. Various linear peptides with amidated C-termini were found to inhibit MDR1 Pgp-mediated DAMGO transport. This group includes endogenous opioid peptides such as adrenorphin and endomorphin 1 and 2, as well as the neurokinin, Substance P. The latter bioactive peptides have a relatively high affinity for the transporter. Transport of endomorphin 1 and 2 could be directly demonstrated by the uptake of the radiolabeled opioid peptides in membrane vesicles from MDR1-transfected cells with a Km of 15 and 12 μM, respectively. This opens the possibility that MDR1 Pgp is involved in the elimination and/or tissue distribution of these bioactive peptides. 相似文献
63.
Newly shed foliar plant litter often has a decomposition rate of ca 0.1–0.2% day–1, which decreases greatly with time and may reach 0.0001 to 0.00001% day–1 or lower in litter material in the last stages of decay. The decrease in decomposability (substrate quality) varies among species and is complex, involving both direct chemical changes in the substrate itself and the succession in microorganisms able to compete for substrate with a given chemical composition. In late stages, the decomposition appears very little affected by climate, suggesting that climate change will have little effect on late-stages decomposition rates. Here, we apply a model for the late stages of litter decomposition to address the question of climate-change effects on soil-C storage. Decomposition of litter turning into soil organic matter (SOM) is determined by the degradation rate of lignin. In the last phases of decay, raised N concentrations have a rate-retarding effect on lignin degradation and thus on the decomposition of far-decomposed litter and litter in near-humus stages. The retardation of the decomposition rate in late stages may be so strong that decomposition reaches a limit value at which total mass losses virtually stop. At such a stage the remaining litter would be close to that of stabilized SOM. The estimated limit values for different species range from about 45 to 100% decomposition indicating that between 0 and 55% should either be stabilized or decompose extremely slowly. For no less than 106 long-term studies on litter decomposition, encompassing 21 litter types, limit values were significantly and negatively related to N concentration, meaning that the higher the N concentration in the newly shed litter (the lower the C/N ratio) the more litter was left when it reached its limit value. Trees growing under warmer and wetter climates (higher actual evapotranspiration, AET) tend to shed foliar litter more rich in N than those growing under colder and drier climates. A change in climate resulting in higher AET would thus mean that within species, e.g., Scots pine, a higher N level in the foliar litter may result. Further, within the boreal system deciduous species appear to have foliar litter richer in N than have conifers and within the conifers group, Norway spruce has needle litter more rich in N than, e.g., Scots pine. Thus, a change of species (e.g., by planting) from pine to spruce or from spruce to a deciduous species such as birch may result in a higher N level in the litter fall at a given site. In both cases the result would be a lower limit value for decomposition. The paper presents an hypothesis, largely based on available data that a change in climate of 4° higher annual average temperature and 40% higher precipitation in the Baltic basin would result in higher N levels in litter, lower decomposition and thus a considerable increase in humus accumulation. 相似文献
64.
A. Klockow-Beck A. Nick St. Geisshuesler D. Schaufelberger 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,720(1-2):141-151
A capillary electrophoresis (CE) method has been developed as an alternative method for the determination of the inorganic degradation products sulfate and sulfamate in topiramate drug product and drug substance, currently performed by ion chromatography. The anions are separated in a background electrolyte containing potassium chromate and boric acid, followed by indirect UV detection. By adding tetradecyltrimethylammonium bromide to the electrolyte, analysis is performed under co-electroosmotic flow conditions. Variations in injection volumes and migration times are compensated for by use of an internal standard. The validation of the method, which was performed according to ICH guidelines (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) [1], comprises specificity, accuracy, linearity, precision, sensitivity and robustness. In addition, the results of an actual tablet sample analysis obtained by this CE method are statistically shown to be in close agreement with those obtained by an ion chromatographic method. 相似文献
65.
H. Wiksell V. Ekstrand C. Wadström G. Auer 《Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)》2009,25(3):128-132
A large and increasing number of women in the western world will at some point during their life be investigated morphologically for some type of breast lesion. Fine Needle Aspiration (FNA) is one morphological method which is considered to be the fastest, cheapest and the most patient-friendly approach. However, the frequency of conclusive samples using this method varies and is often too low, especially when performed by unexperienced operators. In this study we have developed and tested a new semi-automated instrument (“CytoTest”) designed for FNA which is intended to improve the efficacy of the technique by increasing the percentage of conclusive samples. A total of 443 consecutive aspiration procedures on palpable breast lesions were performed to compare this new “CytoTest” equipment with the standard protocol using the same type of needles. We conclude that by increasing the extent and frequency of the reciprocatory motions used by an experienced sampling operator as well as enhancing the ejection pressure, the cellular yield can be increased almost three folded compared to the standard protocol. For cases with high amounts of non-diagnostic material (such as blood or cystic fluid) which were discarded, up to four times more sample could be obtained. Furthermore, the frequency of sparse samples under 1 mg was halved with use of the “CytoTest”. 相似文献
66.
The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change. 相似文献
67.
Stine Lastein Erik Höglund Øyvind Øverli Kjell B. Døving 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2008,194(12):1007-1012
The corticotrophin-releasing factor (CRF) receptors show striking homogeneity throughout the vertebrate subphylum. In mammals, the CRF(1) receptor (CRFR(1)) plays an important role in mediating behavioral and endocrine responses to fear and stress. The specific roles of this receptor subtype in fear and stress reactions in non-mammalian vertebrates are largely unknown. Crucian carp displays the olfactory-mediated fright reaction, a stereotypic behavioral response to waterborne cues from damaged skin of conspecifics. This reaction shows several similarities to basic components of avoidance behavior in mammals. In the present study, we applied the non-peptide CRFR(1) antagonist, antalarmin, to crucian carp 1 h before exposure to conspecific skin extract. This treatment resulted in a suppression of the fright reaction. After skin extract exposure, antalarmin treatment also lead to lower plasma cortisol values, as compared to vehicle treatment. This suppression of the behavioral fright reaction and the stress induced rise in plasma cortisol in crucian carp suggests that the functions of the CRFR(1) are conserved by evolution. 相似文献
68.
Sven Hörstadius 《Development genes and evolution》1923,98(1-2):1-9
Ohne ZusammenfassungDie Untersuchungen wurden an der Zoologischen Station Kristineberg, Schweden, ausgeführt. Es ist mir eine angenehme Pflicht, dem Direktor, Herrn ProfessorHjalmar Théel, und dem Vorstand, Herrn Dr.Hjalmar Östergren, meinen besten Dank auszusprechen. Schließlich richte ich den herzlichsten Dank an Herrn Dr.John Runnström, Stockholm, der mir die Idee der Untersuchung gegeben und mit größtem Interesse und größter Freundlichkeit meine Arbeit geleitet hat. 相似文献
69.
70.