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排序方式: 共有652条查询结果,搜索用时 31 毫秒
1.
Nowak KW Strowski MZ Switonska MM Kaczmarek P Singh V Fabis M Mackowiak P Nowak M Malendowicz LK 《International journal of molecular medicine》2005,15(6):969-972
Orexins are recently identified neuropeptides that appear to play a role in the regulation of energy homeostasis and arousal. They bind to and activate two closely related G protein-coupled receptors (OXR1 and OXR2), previously described as orphans. In this study we examined involvement of orexins in regulation of insulin secretion from rat pancreatic islets utilizing an in situ perfused pancreas and isolated pancreatic islet models. By means of RT-PCR we found that both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the expression levels of OXR1 were higher than OXR2. In both experimental models applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently stimulated insulin secretion at two different glucose concentrations (6.66 or 26.4 mmol/l), with orexin A being more potent than orexin B. This study demonstrates that orexins A and B modulate insulin secretion in vitro. 相似文献
2.
Curcumin is one of the most frequently researched herbal substances; however, it has been reported to have a poor bioavailability and fast metabolism, which has led to doubts about its effectiveness. Curcumin has antioxidant and anti-inflammatory effects, and has demonstrated favorable health effects. Nevertheless, well-reported in vivo pharmacological activities of curcumin are limited by its poor solubility, bioavailability, and pharmacokinetic profile. The bidirectional interactions between curcumin and gut microbiota play key roles in understanding the ambiguity between the bioavailability and biological activity of curcumin, including its wider health impact. 相似文献
3.
Antiparkinsonian-like activity of glutamate receptor antagonists (mostly of N-methyl-D-aspartate (NMDA) receptors) has been demonstrated in animals and for uncompetitive agents, also in humans. In the present study we investigated the potential antiparkinsonian-like activity of compounds acting at the glycine site of the NMDA receptor complex in three animal models of Parkinson's disease and compared them with the new uncompetitive NMDA receptor antagonist MRZ 2/579. Haloperidol-induced catalepsy was inhibited by the Merz glycine site antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 but not by another antagonist L-701,324 or the glycine site partial agonists ACPC and D-CS. None of the tested glycine site antagonists or partial agonists increased locomotor activity or potentiated L-DOPA responses in reserpine and alpha-MT treated rats. In rats with a unilateral 6-OHDA medial forebrain bundle lesion neither glycine site antagonists nor partial agonists affected rotations on their own or enhanced the contralateral rotations induced by L-DOPA. In contrast, the uncompetitive NMDA receptor antagonist MRZ 2/579 was active in all antiparkinsonian tests used in this study. Based on the present data the therapeutic potential of the glycine site antagonists and partial agonists tested for the treatment of Parkinson's disease is rather doubtful. Uncompetitive NMDA receptor antagonists seem to possess a better profile as antiparkinsonian agents. 相似文献
4.
Marzena Karcz-Kubicha Katerina Antoniou Anton Terasmaa Davide Quarta Marcello Solinas Zuzana Justinova Antonella Pezzola Rosaria Reggio Christa E Müller Kjell Fuxe Steven R Goldberg Patrizia Popoli Sergi Ferré 《Neuropsychopharmacology》2003,28(7):1281-1291
The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade. 相似文献
5.
Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study. 总被引:4,自引:0,他引:4
Fabio Efficace Patrick Therasse Martine J Piccart Corneel Coens Kristel van Steen Marzena Welnicka-Jaskiewicz Tanja Cufer Jaroslaw Dyczka Michail Lichinitser Lois Shepherd Hanneke de Haes Mirjam A Sprangers Andrew Bottomley 《Journal of clinical oncology》2004,22(16):3381-3388
PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population. 相似文献
6.
Marzena Ciechomska Caroline L. Wilson Achilleas Floudas Wang Hui Andrew D. Rowan Willem van Eden John H. Robinson Andrew M. Knight 《Immunology》2014,141(1):70-78
The majority of studies examining antigen‐presenting cell (APC) function have focused on the capture and presentation of antigens released from pathogens or damaged cells. However, antigen‐specific B cells are also capable of efficiently extracting antigens that are either tethered to, or integrally part of the plasma membrane of various target cells. In this study we show that B cells are also highly efficient at extracting integral components of the extracellular matrix (ECM) for subsequent presentation. In particular we demonstrate that B cells specific for aggrecan, an integral component of cartilage ECM, acquire this rheumatoid arthritis candidate autoantigen in both a B‐cell‐receptor‐dependent and a contact‐dependent manner. We also demonstrate that the subsequent presentation of aggregan from ECM leads to CD4+ T‐cell activation and effector cell formation. Recent studies have identified B‐cell‐mediated antigen presentation as essential for the development of autoimmunity, but a unique role for B cells compared with other APC has yet to be defined. Our findings lead us to propose that the acquisition of ECM‐derived autoantigens represents a mechanism that defines the APC requirement for B cells in the development of autoimmunity. 相似文献
7.
Andrzej Nowicki Zbigniew Trawinski Barbara Gambin Wojciech Secomski Michał Szubielski Marzena Parol Robert Olszewski 《Ultrasound in medicine & biology》2018,44(6):1187-1197
A high-frequency scanning system consisting of a 20-MHz linear array transducer combined with a 20-MHz pulsed Doppler probe was introduced to evaluate the degree of radial artery flow-mediated dilation (FMD [%]) in two groups of patients after 5?min of controlled forearm ischemia followed by reactive hyperemia. In group I, comprising 27 healthy volunteers, FMD (mean?±?standard deviation) was 15.26?±?4.90% (95% confidence interval [CI]: 13.32%–17.20%); in group II, comprising 17 patients with chronic coronary artery disease, FMD was significantly less at 4.53?±?4.11% (95% CI: 2.42%–6.64%). Specifically, the ratio FMD/SR (mean?±?standard deviation), was equal to 5.36?×?10?4?±?4.64?×?10?4 (95% CI: 3.54?×?10?4 to 7.18?×?10?4) in group I and 1.38?×?10?4?±?0.89?×?10?4 (95% CI: 0.70?×?10?4 to 2.06?×?10?4) in group II. Statistically significant differences between the two groups were confirmed by a Wilcoxon–Mann–Whitney test for both FMD and FMD/SR (p?<0.01). Areas under receiver operating characteristic curves for FMD and FMD/SR were greater than 0.9. The results confirm the usefulness of the proposed measurements of radial artery FMD and SR in differentiation of normal patients from those with chronic coronary artery disease. 相似文献
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