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Objective To study the drug dosage and time dependency characteristics of high-fructose-high-fat-feeding plus dexamethason for inducing the mouse acute fatty liver model and to optimize the condition of drug induced fatty liver model.Methods Male KM mice were divided into the normal control group and high-fructose-high-fat-feeding plus peritoneal injection of dexamethason group.The mice were killed at 3 different time points.The mouse body mass and liver mass were detected.The liver index was calculated.The serum and liver tissue homogenate TG and serum glucose(GLU) levels were detected.The liver tissue pathological change was observed by HE staining.Total RNA reverse expression related gene was extracted from the liver tissue.The total protein was extracted from the liver tissue and the related protein expression was detected by Western Blot.Results Compared with the control group,blood and liver homogenate TG after 7 d in the dexamethason model group was increased,the liver index was increased,the pathological section displayed that the fatty liver was formed.RT-PCR showed that lipid metabolism related gene expression had obvious change.Western Blot showed that SIRT1 was significantly decreased.But with the dexamethason dosage decrease and time extending,the fatty liver related indexes were decreased,lipid metabolic gene PPAR,FOXO3 and FXR were gradually increased,while LXR was gradually decreased and protein SIRT1 was gradually increased.Conclusion High-fructose-high-fatfeeding plus peritoneal injection of dexamethason could establish the mouse acute fatty liver model,moreover the model maintenance has dependency on dexamethason dosage and medication time,which has a guidance significance for the drug interventional experiment.
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<p><b>Objectives:</b> To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers.</p><p><b>Methods:</b> Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed.</p><p><b>Results:</b> UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia.</p><p><b>Conclusions:</b> UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings.</p>
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Objective To investigate the effect of cell proliferation and apoptosis induced by Pingyangmycin (PYM)and dexamethasone (DEX) on human umbilical vein endothelial cells (HUVEC)in vitro, so as to provide therotical evidence for treatment of aneurysm with PYMand DEX. Methods Control, PYM, DEX and PYM group were established after HUVEC were cultured for 24 hours. Cell morphology was observed by inverted microscope.The effect of cell proliferation and apoptosis were detected with CCK-8reagents and flow Cytometry. The apoptotic protein expression of caspase-3 was testedthrough Western blot. Results Descend of adherent cell density and the ascend of floating cells could be observed after treated with PYM and DEX for 24 hours. HUVEC could be inhibited effectively with concentration-dependent on PYM and DEX. The significant statistical difference of cell apoptosis rate between the group used for PYM alone and the group combined low-concentration PYM with DEX through Flow Cytometrywas found. There was significant statistical difference of apoptotic protein expression of caspase-3 through Western blot compared with the group used for PYM alone and the group combined low-concentration PYM with DEX. Conclusion PYM and DEXcould inhibitthe proliferation of HUVEC alone. The better effects could be observed combination low-concentration PYM with DEX , the mechanism of which might beapoptosis with low-concentration PYM and necrosis with high-concentration PYM.
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Objective To investigate the kinetics processes of TLR2 and TLR4 in CD14~+ monocyte of patients during and after cardiac surgery with cardiopulmonary bypass(CPB) and the effects of dexamethasone(DXM) on the regulation of TLR2 and 4 in CD14~+ monocyte. Methods Twenty patients undergoing elective atrial/ventricular septal defect correction were randomized to received 1 mg/kg dexamethasone or placebo before induction of anesthesia. The CD14~+ monocyte surface TLR2 and TLR4 and the intracellular HSP70 were stained and analyzed by flow cytometry, and plasma level of TNF-?, IL-6, IL-10, NO and MDA were measured at following times: before the dexamethasone or placebo were administer(T1), before starting CPB(T2), immediately after aortic declamping(T3), 30min after aortic declamping(T4), 5h after skin closure(T5) and 24h after skin closure(T6). Results Both the HSP70~+ TLR2~+ monocytes and HSP70~+-TLR4~+ monocytes,the plasma concentration of TNF-?, IL-6, NO and IL-10 were upregulated after introduction (P