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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
981.
982.
983.
In mammals, the pineal hormone melatonin activates G protein-coupled MT(1) and MT(2) melatonin receptors. Acute exposure of recombinant MT(1) and MT(2) melatonin receptors to supraphysiological concentrations of melatonin differentially regulates these two receptors with the MT(2), but not the MT(1), exhibiting rapid desensitization and internalization. In the present study, we sought to determine whether prolonged exposure to supraphysiological and physiological concentrations of melatonin desensitized and/or internalized the MT(1) melatonin receptor. Using a Chinese hamster ovary (CHO) cell line stably expressing MT(1)-FLAG or transiently expressing MT(1)-green fluorescent protein (GFP) melatonin receptors, we found that prolonged exposure (8h) to supraphysiological concentrations of melatonin (100 nM) significantly increased the number of MT(1) melatonin receptors and decreased the affinity (K(i)) of melatonin for competition for 2-[125]iodomelatonin. A similar treatment also desensitized the MT(1) melatonin receptor-mediated stimulation of [(35)S]GTPgammaS binding, but did not internalize the receptor. In contrast, prolonged exposure to a concentration of melatonin mimicking nocturnal levels (400 pM) did not affect the number of MT(1) melatonin receptors, the affinity for melatonin, or the functional sensitivity of the receptor. We conclude that in vivo endogenous melatonin does not significantly affect the functional sensitivity of MT(1) melatonin receptors, however, exogenous melatonin taken therapeutically at doses above physiological levels could desensitize the receptor thereby affecting physiological responses mediated following activation of MT(1) melatonin receptors. 相似文献
984.
Stórustovu Sí Sánchez C Pörzgen P Brennum LT Larsen AK Pulis M Ebert B 《British journal of pharmacology》2004,142(1):172-180
1. Clinical observations with the selective serotonin reuptake inhibitor (SSRI), S-citalopram, indicate that S-citalopram is more efficacious and produces earlier symptom relief than RS-citalopram. Since R-citalopram is at least 20-fold weaker than S-citalopram as inhibitor of the 5-HT transporter (SERT) in preclinical studies, the clinical data suggest an unexpected antagonistic interaction between the two enantiomers. We therefore characterised the interaction of R- and S-citalopram with the SERT in in vivo and in vitro assays. 2. In both behavioural (potentiation of 5-hydroxytryptophan (5-HTP)-induced behaviour) and electrophysiological studies (inhibition of 5-HT-elicited ion currents in Xenopus oocytes expressing the human SERT (hSERT) R-citalopram inhibited the effects of S-citalopram in a dose-dependent manner. With S-citalopram : R-citalopram ratios of 1 : 2 and 1 : 4, 5-HTP potentiation was significantly smaller than with S-citalopram alone. 3. R-citalopram did not antagonise the effects of another SSRI (fluoxetine) in either behavioural or electrophysiological studies. 4. In oocytes, inhibition of hSERT-mediated currents by R-citalopram was almost completely reversible and characterised by fast on- and off-sets of action. In contrast, the off-set for S-citalopram was 35-fold slower than for R-citalopram. 5. Kinetic analysis of the oocyte experiments suggests that S-citalopram binding to SERT induces a long-lasting, inhibited state of the transporter and that coapplication of R-citalopram partially relieves SERT of this persistent inhibition. 6. We propose that the kinetic interaction of R- and S-citalopram with SERT is a critical factor contributing to the antagonistic effects of R-citalopram on S-citalopram in vitro and in vivo. 相似文献
985.
OBJECTIVE: Data from a large, nationally representative sample of hospital emergency departments (EDs) were used to assess the prevalence and characteristics of alcohol-related ED visits among people ages 13 to 25 years in the United States. METHOD: Emergency department visits recorded in the National Electronic Injury Surveillance System-All Injury Program were coded for alcohol involvement based on alcohol product codes and abstractions of chart narratives. National estimates and confidence intervals were calculated using SUDAAN statistical software. RESULTS: Based on these chart data, in the United States in 2001 there were an estimated 244,331 alcohol-related ED visits among people ages 13 to 25 (3.2% of total visits). Of these, an estimated 119,503 (49%) involved people below the legal drinking age of 21. The number of alcohol-related visits increased throughout adolescence and young adulthood to the age of 21, after which they decreased to levels similar to those seen for 18 to 20 year olds. Alcohol-related visits were most frequent on weekends and among males and were more strongly associated with visits related to assault or self-harm than to visits for unintentional injuries or injuries of unknown intent. In this population, 38% of alcohol-related visits involved no external cause of injury (e.g., drinking to excess only). CONCLUSIONS: These data highlight the need for stronger efforts to delay initiation of alcohol use among adolescents as long as possible and to limit access to alcohol for underage drinkers. 相似文献
986.
Recombinant human thyroid-stimulating hormone (rhTSH), used to enhance diagnostic radioiodine whole body scanning and thyroglobulin testing, has dramatically altered the management of patients with thyroid cancer. Withdrawal from thyroid hormone suppression therapy and subsequent hypothyroidism is no longer the only safe and effective method for thyroid cancer surveillance. Currently, rhTSH is only approved for the monitoring of low-risk patients with well-differentiated thyroid cancer and radioactive iodine administration, in selected cases. Additional applications of rhTSH include enhancing the sensitivity of positron emission tomography in thyroid cancer, the management of multinodular goiter, and dynamic testing of thyroid reserve. The diagnostic and therapeutic role of rhTSH in these areas is discussed in this review. 相似文献
987.
Marongiu B Porcedda S Piras A Rosa A Deiana M Dessì MA 《Phytotherapy research : PTR》2004,18(10):789-792
The antioxidant activity of Melissa officinalis subsp. officinalis and of Melissa officinalis subsp. inodora extracts, obtained by using carbon dioxide under supercritical conditions was investigated. The samples were prepared in two steps. A preliminary extraction at 90 bar and 50 degrees C eliminated the essential oil, then a further extraction at 300 bar and 50 degrees C obtained the high molecular mass extract. These samples were tested for autoxidation and the iron or EDTA-mediated oxidation of linoleic acid at 37 degrees C in the absence of solvent, in in vitro systems. During linoleic acid autoxidation and its EDTA-mediated oxidation both M. officinalis and M. inodora extracts showed an antioxidant activity, and no significant differences in their efficacy were observed. None showed any prooxidant activity. 相似文献
988.
Martin RF Broadhurst S Reum ME Squire CJ Clark GR Lobachevsky PN White JM Clark C Sy D Spotheim-Maurizot M Kelly DP 《Cancer research》2004,64(3):1067-1070
New analogues of the minor groove binding ligand Hoechst 33342 have been investigated in an attempt to improve radioprotective activity. The synthesis, DNA binding, and in vitro radioprotective properties of methylproamine, the most potent derivative, are reported. Experiments with V79 cells have shown that methylproamine is approximately 100-fold more potent than the classical aminothiol radioprotector WR1065. The crystal structures of methylproamine and proamine complexes with the dodecamer d(CGCGAATTCGCG)(2) confirm that the new analogues also are minor groove binders. It is proposed that the DNA-bound methylproamine ligand acts as a reducing agent by an electron transfer mechanism, repairing transient radiation-induced oxidizing species on DNA. 相似文献
989.
The potential of antigen-directed cancer immunotherapy has not been fully realized, perhaps because many commonly targeted tumor associated proteins are not essential to maintaining the malignant cell phenotype. A constitutively activating mutation in the signaling molecule BRAF is expressed frequently in melanomas and may play an important role in the biology of this disease. A 29-mer B-Raf peptide incorporating the V599E mutation was used for in vitro stimulation of lymphocytes derived from melanoma patients, generating MHC class II-restricted CD4(+) T cells specific for this peptide as well as for melanoma cells expressing B-Raf V599E. Mutated B-Raf exemplifies targets that may be ideal for immunotherapy. 相似文献
990.
Akt stimulates aerobic glycolysis in cancer cells 总被引:26,自引:0,他引:26
Elstrom RL Bauer DE Buzzai M Karnauskas R Harris MH Plas DR Zhuang H Cinalli RM Alavi A Rudin CM Thompson CB 《Cancer research》2004,64(11):3892-3899
Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival. 相似文献