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1.
Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ12,14PGJ2 a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ12,14PGJ2 production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ2 and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment. 相似文献
2.
目的探讨维生素D(VitD)联合鱼油对糖尿病前期(PDM)患者糖脂代谢、胰岛β细胞功能的影响。 方法选取PDM患者132例,随机均分为联合组(VitD+鱼油)、VitD组(VitD)和对照组(不干预)。比较各组糖脂代谢、胰岛β细胞功能、炎症反应、血管内皮功能等指标。 结果与干预前比较,干预后联合组甘油三酯降低,白细胞介素-10增高(P<0.05),联合组和VitD组低密度脂蛋白胆固醇、肿瘤坏死因子-α、胰岛素抵抗指数、前列腺素E2、瘦素、抵抗素降低(P<0.05),空腹胰岛素、胰岛β细胞功能指数、脂联素增高(P<0.05),且联合组改善更为明显(P<0.05)。 结论维生素D联合鱼油治疗PDM患者可改善其脂代谢和胰岛功能相关指标,具有一定临床应用价值。 相似文献
3.
目的:探讨前列腺素E联合连续肾替代治疗(CRRT)对脓毒症合并急性肾损伤(AKI)患者预后的影响。方法:选取89例脓毒症合并AKI患者为研究对象,采用随机数字表法分为对照组(n=44)和观察组(n=45),分别采取CRRT及前列腺素E联合CRRT治疗。比较2组患者预后转归情况,检测并比较2组患者治疗前后血清炎性因子、肾功能及免疫功能指标。结果:观察组ICU治疗时间及住院时间较对照组明显缩短(P<0.05);对照组死亡14例(31.82%),观察组死亡9例(20.00%),2组患者死亡率无明显差异(P>0.05)。与治疗前比较,治疗后2组血清TNF-α、IL-6、hs-CRP含量降低,BUN、SCr含量升高(P<0.05),且观察组上述指标均低于对照组(P<0.05)。与治疗前比较,治疗后2组CD4+/CD8+及观察组NK细胞比例及IgG、IgA、IgM含量均明显升高(P<0.05),且观察组高于对照组(P<0.05)。与治疗前比较,治疗后2组Marshall评分、APACHEⅡ评分下降(P<0.05),且观察组低于对照组(P<0.05)。结论:前列腺素E联合CRRT治疗脓毒症合并AKI可显著降低患者炎性因子水平,改善患者肾功能和免疫功能,效果优于单独CRRT治疗。 相似文献
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目的目的探讨选择性环氧化酶-2(COX-2)抑制剂Celebrex对人卵巢癌细胞HO-8910的抑制作用及其机制。方法选用HO-8910体外培养,应用四甲基偶氮唑蓝(MTT)法、逆转录聚合酶链反应和酶联免疫吸附试验检测Celebrex对HO-8910细胞生长以及COX-2 mRNA、前列腺素E2(PGE2)和白介素-6(IL-6)蛋白表达的影响。结果 Celebrex对HO-8910细胞的生长具有抑制作用,其效应具有时间-剂量依赖性,在达到一定作用时间和剂量时能明显降低PGE2和IL-6蛋白的表达,但不影响COX-2 mRNA的表达。结论 Celebrex可能主要是通过抑制COX-2活性及PGE2和IL-6等的表达而对卵巢癌发挥抑制效应。 相似文献
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Lachmann S Kimmerle-Müller E Axmann D Scheideler L Weber H Haas R 《Clinical oral implants research》2007,18(2):212-223
OBJECTIVES: To assess possible relationships between peri-implant crevicular fluid (PICF) volumes, biochemical markers of the peri-implant immune response, and periodontitis-associated genotype. MATERIAL AND METHODS: PICF samples from 29 implant maintenance patients, 24 wearing overdentures, five having single crowns and bridgework (11 patients with peri-implantitis and 18 individuals with healthy peri-implant conditions), were analyzed for per site and per crevicular-fluid-volume concentrations of interleukin-1beta, plasminogen activator inhibitor type 2, and prostaglandin E2 by ELISA. Associations between the three substance concentrations and to crevicular fluid flow rate were analyzed by linear regression analysis. The possible differentiating influence of the composite interleukin-1A and -1B genotype on the patients' peri-implant health and biochemical inflammatory status was checked formally with t-test statistics and the Wilcoxon' test. One implant per patient was chosen for analysis. RESULTS: In patients with healthy peri-implant conditions, genotype-positive individuals showed elevated crevicular fluid flow rates and at the same time reduced mediator concentrations. In patients with an implant affected from peri-implantitis, no statistically significant influence of the periodontitis-associated genotype around the fixture can be stated. There was no statistical difference between per site and per crevicular-fluid-volume concentration analyses. All three mediator concentrations were positively related to each other, while there was a strong negative correlation between crevicular fluid volume and plasminogen activator inhibitor 2 or prostaglandin E2. CONCLUSIONS: The Interleukin-1 polymorphism investigated exerted only little influence on the peri-implant crevicular immune response, and this influence appeared to be of limited impact in sites with established peri-implantitis lesions. 相似文献
9.
J. B. Payne G. K. Johnson R. A. Reinhardt J. K. Dyer C. A. Maze D. G. Dunning 《Journal of periodontal research》1996,31(2):99-104
Cigarette smoking is a major risk factor in the development and further progression of periodontitis. However, little is known regarding the pathogenesis of smoking-related periodontal diseases. The purpose of this study was to examine the effects of nicotine, alone and in combination with lipopolysaccharide (LPS), on monocyte secretion of bone-resorbing factors, PGE2 and IL-1β. Peripheral blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from 15 healthy, non-smoking donors. PBM were incubated for 24 h in RPMI 1640 containing nicotine (0, 50 μg/ml, I μg/ml, 10 μg/ml and 100 μg/ml) with or without 10 μg/ml Porphyromonas gingivalis LPS or Escherichia coli LPS. Culture supernatants were assayed for PGE2 and IL-1β by ELISA. None of the nicotine preparations resulted in significant PBM secretion of PGE2 and IL-1β above that of unstimulated cultures. However, PGE2 release was potentiated 1.7-fold by the combination of P. gingivalis LPS and 10 μg/ml nicotine relative to P. gingivalis LPS alone (p<0.05, one-way ANOVA). Prostaglandin E3 release also was potentiated 3.5-fold by P. gingivalis LPS and 100 μg/ml nicotine relative to P. gingivalis LPS alone (p<0.00001, one-way ANOVA) and 3.1-fold by E. coli LPS and 100 μg/ml nicotine relative to E. coli LPS alone (p<0.00001, I. one-way ANOVA). IL-1β secretion was lower for either LPS plus 100 μg/ml nicotine relative to LPS alone, although not significantly. These data demonstrate upregulation of LPS-mediated monocyte secretion of PGE2 by nicotine and suggest a potential role for nicotine in periodontal disease pathogenesis. 相似文献
10.
G. K. Johnson T. K. Poore C. A. Squier P. W. Wertz R. A. Reinhardt S. D. Vincent 《Journal of periodontal research》1994,29(6):430-438
Inflammatory mediators released as a result of smokeless tobacco (ST)-induced irritation may play a role in the development of oral mucosal lesions at habitual tobacco placement sites in ST users. The present study examined levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) in ST-induced mucosal lesions and compared these to mediator levels in clinically normal mucosa. Soft tissue biopsies were obtained from white mucosal lesions at habitual placement sites and normal alveolar mucosal tissue at non-placement sites in 18 ST users. Fifteen non-tobacco using subjects also provided normal alveolar mucosal biopsies. IL-1 and PGE2 were recovered from the specimens, and mediator levels were determined by enzyme immunoassay. Prostaglandin E2 levels (pg/mg) were lower in both regions in the ST subjects, but values did not vary significantly between the regions with 2.77±0.72 and 2.86±0.99 at placement and non-placement sites, respectively, in ST users and 7.31±3.84 in non-tobacco users. Both IL-1α and IL-lβ (pg/mg) were significantly (p < 0.0I) elevated in ST lesions (IL-lã=25.56±4.00; IL-1β=7.76±1.68) compared to either non-placement sites in ST users (IL-lα=14.64±2.65; IL-lβ=1.63±0.72) or non-tobacco users (IL-lα=12.84±2.60; IL-lβ=2.04±0.75). In view of IL-l's role in keratinocyte proliferation and its inflammatory effects, this cytokine may contribute to mucosal and gingival alterations observed in ST users. 相似文献