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排序方式: 共有3516条查询结果,搜索用时 15 毫秒
41.
王存解 《临床合理用药杂志》2015,(23)
目的:探讨亚临床甲状腺功能减退症(SCH)与急性冠脉综合征患者血脂、脑钠肽(BNP)、空腹血糖(FBG)、血肌酐(Scr)、血清同型半胱氨酸(Hcy)的关系。方法选取 ACS 患者468例,根据甲状腺功能是否正常分为甲状腺功能正常组(EUT 组)426例和 SCH 组42例。按照住院病历资料记录患者的年龄、吸烟史、身高、体质量和血压,计算体质量指数。检测 FBG、BNP、Hcy、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、促甲状腺素(TSH)、甲状腺激素和 Scr。结果 SCH 组患者的年龄、Scr、FBG、BNP 和 TSH 水平明显高于 EUT 组,差异均有统计学意义(P ﹤0.05或0.01)。结论 SCH 可影响 ACS 患者的 BNP、Scr、FBG 及 TSH 等代谢,重视纠正甲状腺功能有利于改善 ACS 患者的预后。 相似文献
42.
Iksoo Kim Hyeongmin Kim Jieun Ro Kanghee Jo Sandeep Karki Prakash Khadka Gyiae Yun Jaehwi Lee 《Biomolecules & therapeutics.》2015,23(3):296-300
β-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of β-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of β-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of β-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of β-lapachone was 15.5%. The considerable degradation of β-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of β-lapachone may be resulted from the first-pass metabolic degradation of β-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility. 相似文献
43.
Recent trends in preclinical drug–drug interaction studies of flavonoids — Review of case studies,issues and perspectives 下载免费PDF全文
Nuggehally R. Srinivas 《Phytotherapy research : PTR》2015,29(11):1679-1691
Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug–drug interaction potential between flavonoids and co‐ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti‐cancer drugs to enhance the bioavailability of anti‐cancer drugs and thereby reduce the dose size of the anti‐cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co‐administered drugs. The relevance of combination of flavonoids with anti‐cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
44.
Han Shen Stephanie Decollogne Pierre J Dilda Eric Hau Sylvia A Chung Peter P Luk Philip J Hogg Kerrie L McDonald 《Journal of experimental & clinical cancer research : CR》2015,34(1)
Background
Glioblastoma (GBM) is the most common and malignant primary brain tumor. In contrast to some other tumor types, aberrant glucose metabolism is an important component of GBM growth and chemoresistance. Recent studies of human orthotopic GBM in mice and in situ demonstrated GBM cells rely on both glycolysis and mitochondrial oxidation for glucose catabolism. These observations suggest that the homeostasis of energy metabolism of GBM cells might be further disturbed by dual-inhibition of glucose metabolism. The present study aimed to evaluate the efficacy and the mechanisms of dual-targeting therapy in GBM cells.Methods
Representative GBM cells (immortalized GBM cell lines and patient-derived GBM cells) and non-cancerous cells were treated with 4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid (PENAO), an in-house designed novel arsenic-based mitochondrial toxin, in combination with dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor. The efficacy of this combinatorial therapy was evaluated by MTS assay, clonogenic surviving assay and apoptotic assays. The underlying mechanisms of this dual-targeting treatment were unraveled by using mitochondrial membrane potential measurements, cytosol/mitochondrial ROS detection, western blotting, extracellular flux assay and mass spectrometry.Results
As monotherapies, both PENAO and DCA induced proliferation arrest in a panel of GBM cell lines and primary isolates. PENAO inhibited oxygen consumption, induced oxidative stress and depolarized mitochondrial membrane potential, which in turn activated mitochondria-mediated apoptosis. By combining DCA with PENAO, the two drugs worked synergistically to inhibit cell proliferation (but had no significant effect on non-cancerous cells), impair the clonogenicity, and induce mitochondria-mediated apoptosis. An oxidative stress of mitochondrial origin takes a prominent place in the mechanism by which the combination of PENAO and DCA induces cell death. Additionally, PENAO-induced oxidative damage was enhanced by DCA through glycolytic inhibition which in turn diminished acid production induced by PENAO. Moreover, DCA treatment also led to an alteration in the multidrug resistance (MDR) phenotype of GBM cells, thereby leading to an increased cytosolic accumulation of PENAO.Conclusions
The findings of this study shed a new light with respect to the dual-targeting of glucose metabolism in GBM cells and the innovative combination of PENAO and DCA shows promise in expanding GBM therapies. 相似文献45.
Ritu Arora David Schmitt Balasubramanyam Karanam Ming Tan Clayton Yates Windy Dean-Colomb 《Oncotarget》2015,6(2):662-678
Metabolism is an important differentiating feature of cancer cells. Lactate dehydrogenases (LDH) A/B are metabolically important proteins and are involved in the critical step of inter-conversion of lactate to pyruvate. Panepoxydone (PP), a natural NF-kB inhibitor, significantly reduces the oxygen consumption and lactate production of MCF-7 and triple negative (MDA-MB-231, MDA-MB-468 and MDA-MB-453) breast cancer cells. We further observed that PP inhibited mitochondrial membrane potential and the ATP synthesis using flow cytometry. PP also up-regulated LDH-B and down-regulated LDH-A expression levels in all breast cancer cells to similar levels observed in HMEC cells. Over-expression of LDH-B in cancer cell lines leads to enhanced apoptosis, mitochondrial damage, and reduced cell migration. Analyzing the patient data set GDS4069 available on the GEO website, we observed 100% of non TNBC and 60% of TNBC patients had less LDH-B expression than LDH-A expression levels. Herein we report a new term called Glycolytic index, a novel method to calculate utilization of oxidative phosphorylation in breast cancer cells through measuring the ratio of the LDH-B to LDH-A. Furthermore, inhibitors of NF-kB could serve as a therapeutic agent for targeting metabolism and for the treatment of triple negative breast cancer. 相似文献
46.
Wafa Hassen Alboukadel Kassambara Thierry Reme Surinder Sahota Anja Seckinger Laure Vincent Guillaume Cartron Jér?me Moreaux Dirk Hose Bernard Klein 《Oncotarget》2015,6(8):6431-6447
Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival. MMCs of patients with a favourable outcome have an increased expression of genes coding for xenobiotic receptors (RXRα, LXR, CAR and FXR) and accordingly of their gene targets, influx transporters and phase I/II DMEs. On the contrary, MMCs of patients with unfavourable outcome displayed a global down regulation of genes coding for xenobiotic receptors and the downstream detoxification genes but had a high expression of genes coding for ARNT and Nrf2 pathways and ABC transporters. Altogether, these data suggests ARNT and Nrf2 pathways could be involved in MM primary resistance and that targeting RXRα, PXR, LXR and FXR through agonists could open new perspectives to alleviate or reverse MM drug resistance. 相似文献
47.
目的 观察瑞波西汀对氯氮平所致代谢综合征的改善作用,以及对慢性精神分裂症患者生活质量的影响.方法 将110例男性慢性精神分裂症患者分为研究组和对照组各55例,疗程24周,分别于治疗前及治疗后24周末测定体重、BMI、腰围、臀围、WHR、空腹血糖、血脂、血浆胰岛素(INS)水平等指标,采用生活质量综合评定问卷(GQOLI-74)评定对生活质量改善情况;以不良反应量表(TESS)评定不良反应.结果 治疗24周后,研究组体重、体重指数(BMI)、腰围、臀围、腰臀比(WHR)、TG、TC、LDL、VLDL、血浆胰岛素(INS)均低于治疗前,HDL高于治疗前,治疗前后比较差异有统计学意义,与对照组比较差异亦有统计学意义(P<0.05),血糖无明显改变.GQOLI-74躯体健康维度、心理功能维度、社会功能维度及总分得分均高于对照组,差异有统计学意义(P<0.01).研究组失眠、便秘、出汗患者比例高于对照组,差异有统计学意义(P<0.05).结论 瑞波西汀可有效改善氯氮平所致的代谢综合征,提高慢性精神分裂症患者的生活质量. 相似文献
48.
49.
Major factors linking mitochondrial dysfunction with myocardial injury are analyzed along with protective mechanisms elicited
by endogenous processes and pharmacological treatments. In particular, a reduced rate of ATP hydrolysis and a slight increase
in ROS formation appear to represent the prevailing components of self-defense mechanisms, especially in the case of ischemic
preconditioning. These protective processes are activated by signaling pathways, which converge on mitochondria activating
the mitochondrial KATP channels and/or inhibiting the mitochondrial permeability transition pore. These pathways can also be stimulated by pharmacological
treatments. Another major goal for cardioprotection is decreasing the burst in mitochondrial ROS formation that characterizes
post-ischemic reperfusion. Finally, mitochondrial targets for therapeutic intervention may include the switch of substrate
being utilized, because inhibition of fatty acid oxidation is associated with cardioprotective effects.
Fabio Di Lisa and Paolo Bernardi are recipients of grants from CNR and MIUR. 相似文献
50.
《Drug metabolism reviews》2012,44(1):61-86
In drug design, it is crucial to have reliable information on how a chemical entity behaves in the presence of metabolizing enzymes. This requires substantial experimental efforts. Consequently, being able to predict the likely site/s of metabolism in any compound, synthesized or virtual, would be highly beneficial and time efficient.In this work, six different methodologies for predictions of the site of metabolism (SOM) have been compared and validated using structurally diverse data sets of drug-like molecules with well-established metabolic pattern in CYP3A4, CYP2C9, or both. Three of the methods predict the SOM based on the ligand's chemical structure, two additional methods use structural information of the enzymes, and the sixth method combines structure and ligand similarity and reactivity. The SOM is correctly predicted in 50 to 90% of the cases, depending on method and enzyme, which is an encouraging rate. We also discuss the underlying mechanisms of cytochrome P450 metabolism in the light of the results from this comparison. 相似文献