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ABSTRACT: The dibenzodiazepine derivative is a so-called "atypical" or second-generation antipsychotic that is widely regarded as one of the most effective drug treatments for schizophrenia and depression. Quetiapine and olanzapine are novel atypical antipsychotic agents that possess much improved tolerability. To the best of our knowledge, FDA has reported three cases of olanzapine-induced interstitial nephritis. Yet there have been no known clinical reports that associate quetiapine treatment with chronic interstitial nephritis (CIN). Here, we report the occurrence of CIN in the presence of edema during quetiapine and olanzapine therapy.
Renal Failure 04/2013; · 0.82 Impact Factor
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ABSTRACT: To explore the role of indoleamine-pyrrole 2,3-dioxygenase (IDO), an immunomodulatory enzyme, in renal cell carcinoma (RCC).
A total of 40 patients diagnosed as RCC in the Second Xiangya Hospital were included in this study. All patients received nephrectomy. The histopathological features of samples were assessed semi-quantitatively. IDO mRNA level in RCC and non-RCC renal tissues was determined by real-time quantitative PCR (RT-qPCR). And the expression of IDO protein in endothelial cells was examined by immunohistochemistry; a Kaplan-Meier survival curves was calculated on the basis of IDO mRNA level.
Level of IDO mRNA in RCC samples was significantly higher than that in tumor-free samples with P<0.001. Patients with high IDO expression had an significantly longer survival time than those with low IDO expression (P=0.01). There was a statistically significant inverse correlation between IDO and proliferation marker Ki67. Patients with high IDO level were of low Ki67 level, and vice versa (P<0.01).
IDO might be a prognostic biomarker for patients with RCC.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 07/2012; 37(7):649-55.
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ABSTRACT: The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF-beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells.
HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml). The morphological changes of HK-2 cells were observed under an inverted microscope. Expression of alpha-SMA was detected by Western blot and immunofluorescence. The protein expression of ZO-1, fibronectin, CTGF, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) were evaluated by Western blot.
Through down-regulation of p-Smad2 and p-Smad3 proteins, AKF-PD significantly inhibited protein expression of alpha-SMA, fibronectin, and CTGF. Meanwhile, the depressed ZO-1 expression and morphological changes induced by TGF-beta1 were attenuated by AKF-PD.
AKF-PD acts as an anti-fibrotic agent through blocking TGF-beta/Smads signaling and consequently inhibits TGF-beta1-induced EMT and CTGF expression in human proximal tubular epithelial cells.
Pharmazie 12/2011; 66(12):961-7. · 1.01 Impact Factor
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Ling Hao Wang,
Ji Shi Liu,
Wang Bin Ning,
Qiong Jing Yuan,
Fang Fang Zhang,
Zhang Zhe Peng,
Miao Miao Lu,
Ren Na Luo, Xiao Fu,
Gao Yun Hu,
Zhao He Wang,
Li Jian Tao
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ABSTRACT: Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of the present study was to investigate the effects of AKF-PD on diabetic nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of action.
We administered AKF-PD to diabetic db/db mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations.
AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the db/db mice. The upregulated expression of α₁(I)- and α₁(IV)-collagen and fibronectin mRNAs, transforming growth factor-β1 (TGF-β₁), α-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins was inhibited by AKF-PD treatment in the renal cortex of db/db mice. The maximal effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the upregulated expression of α₁(I)- and α₁(IV)-collagens, TGF-β₁, TIMP-1 and α-SMA induced by high glucose concentrations in cultured mesangial cells.
Our data indicate that AKF-PD diminishes the abnormal accumulation of mesangial matrix through the inhibition of upregulated expression of TGF-β target genes in kidneys of db/db mice, resulting in attenuation of renal fibrosis and amelioration of renal dysfunction despite persistent hyperglycemia. Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the treatment of diabetic nephropathy.
Pharmacology 08/2011; 88(1-2):88-99. · 1.79 Impact Factor
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ABSTRACT: To investigate the effect of rosuvastatin on atherosclerosis in apoE-knockout (apoE-/-) mice.
Eighteen 6-week-old apoE-/- mice fed with high fat diet were used as atherosclerosis models, twelve 6-week-old C57BL/6 mice fed with normal diet were used as control. After twelve weeks, six apoE-/- mice were used to observe the formation of atherosclerosis. Another 12 apoE-/- mice were divided into placebo treated group (n = 6) and rosuvastatin group (n = 6, 10 mg×kg(-1)×d(-1) per gavage) and treated for 12 weeks. Then, blood was collected for measuring lipid, aorta was prepared for morphologic study (HE, Oil red O, Masson) and immunohistochemical analysis (α-smooth active protein, transforming growth factor β(1), macrophage surface molecule-3).
Serum cholesterol and low density lipoprotein levels were significantly higher in apoE-/- mice fed with high fat diet than in C57/BL6 mice(all P < 0.01)while triglyceride level was similar between the two groups, these were not affected by rosuvastatin. Similarly, atherosclerotic lesion area in apoE-/- mice fed with high fat diet was also not significantly reduced by rosuvastatin, while lipid deposition could be significantly reduced and collagen deposition could be significantly increased in the aortic atherosclerotic lesions by treatment with rosuvastatin. Upregulated TGF-β(1) and Mac-3 expression in the aortic atherosclerotic lesions in apoE-/- mice fed with high fat diet could also be significantly reduced by rosuvastatin (all P < 0.01), suggesting reduce inflammatory responses in the atherosclerotic lesion and stable atherosclerotic plaque post rosuvastatin treatment.
Reducing inflammatory responses and stabilizing plaque properties might contribute to the anti-atherosclerosis effects of rosuvastatin in mice high fat diet fed apoE-/- mice.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 08/2011; 39(8):743-8.
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Qiongjing Yuan,
Rui Wang,
Yu Peng, Xiao Fu,
Wei Wang,
Linghao Wang,
Fangfang Zhang,
Zhangzhe Peng,
Wangbin Ning,
Gaoyun Hu,
Zhaohe Wang,
Lijian Tao
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ABSTRACT: Novel therapeutic agents are urgently needed to combat renal fibrosis. The purpose of this study was to assess, using complete unilateral ureteral obstruction (UUO) in rats, whether fluorofenidone (AKF-PD) [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone] inhibits renal fibrosis, and to determine whether it exerts its inhibitory function on renal fibroblast activation.
Sprague-Dawley rats were randomly divided into 3 groups: sham operation, UUO and UUO/AKF-PD (500 mg/kg/day). Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-β(1), collagen III, α-SMA, p-Smad2, p-Smad3, p-ERK1/2, p-JNK and p-p38 were measured. In addition, the expressions of α-SMA, fibronectin, CTGF, p-Smad2/3, p-ERK1/2, p-p38 and p-JNK were measured in TGF-β(1)-stimulated normal rat renal fibroblasts (NRK-49F).
AKF-PD treatment significantly attenuated tubulointerstitium damage, ECM deposition, the expressions of TGF-β(1), collagen III, α-SMA, p-ERK1/2, p-p38 and p-JNK in vivo. In vitro, AKF-PD dose-dependently inhibited expressions of α-SMA, fibronectin and CTGF. Furthermore, AKF-PD did not inhibit Smad2/3 phosphorylation or nuclear accumulation, but rather attenuated ERK, p38 and JNK activation.
AKF-PD treatment inhibits the progression of renal interstitial fibrosis in obstructed kidneys; this is potentially achieved by suppressing fibroblast activation. Therefore, AKF-PD is a special candidate for the treatment of renal fibrosis.
American Journal of Nephrology 01/2011; 34(2):181-94. · 2.54 Impact Factor
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ABSTRACT: To explore the application of external jugular catheter in hemodialysis patients and provide a new means of inserting tube.
Data of patients who applied the external jugular venous catheter from January 2000 to December 2007 in Second Xiangya hospital were retrospectively analyzed. We observed the time of indwelling catheter, blood flow, tube associated complications and the adequacy of dialysis.
External jugular vein catheters were performed in 856 patients, the successful ratio was 93.22% (798 cases). In total, 223 with dual lumen and 575 with single lumen. The average time of indwelling catheter was (3.46+/-2.21) months. Altogether 405 patients were followed up until the end-point of the investigation, accounting for 50.75å.The average time was (3.12+/-1.22) months. Causes for withdrawal were internal fistula, death, renal transplantation, infection,poor blood flow, etc. Thirty-two patients (4.01%) had the blood flow lower than 150 mL/min(18 of dual lumen catheter), 20 improved through position adjustment and urokinase. The decreasing ratio of BUN in 100 patients after dialysis treatment was about 70%, and the average Kt/V was 1.37+/-0.35, which had no significant difference comparing with that of patients using internal jugular venous catheter (Kt/V=1.39+/-0.33, n=100).Main acute complications of catherizations included 4 local hematoma (0.5%) and 3 bleeding (0.38%). Infection was the major complication in the course of indwelling catherizations, including 32 (4.01%) with local skin infection, 26 (3.26%) catheter infections and 6 (0.75%) with catheter thromboses.
External jugular vein catheterization in hemodialysis is simple,with no serious complications and can provide adequate blood flow. It may be recommended for the patients with visible jugular vein.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 12/2008; 33(11):1056-9.
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Fu-you Liu,
Li Xiao,
You-ming Peng,
Shao-bin Duan,
Hong Liu,
Ying-hong Liu,
Gui-hui Ling,
Fang Yuan,
Jun-xiang Chen, Xiao Fu,
Jian-lian Zhu
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ABSTRACT: The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor beta1 (TGF-beta1) plays a key role in regulating tissue repair and remodelling after injury. Connective tissue growth factor (CTGF), a downstream mediator of TGF-beta1 inducing fibrosis, has been implicated in peritoneal fibrosis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis that can hasten peritoneal fibrosis. In this study, we investigated the effect of small interfering RNA (siRNA) of CTGF by pRETRO-SUPER (PRS) retrovirus vector on the expression of CTGF and VEGF in human peritoneal mesothelial cells.
Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect human peritoneal mesothelial cell (HPMC). The cells were divided into seven groups: low glucose DMEM, low glucose DMEM + TGF-beta1 5 ng/ml, low glucose DMEM + TGF-beta1 5 ng/ml + PRS-CTGF-siRNA(1-4) and low glucose DMEM + TGF-beta1 5 ng/ml + PRS. The expression of CTGF and VEGF were measured by semiquantitative RT-PCR and Western blot.
Low levels of CTGF and VEGF were detected in confluent HPMCs. Following stimulation with TGF-beta1, the levels of CTGF and VEGF were significantly upregulated (P < 0.01). Introduction of PRS-CTGF-siRNA(1-4) resulted in the significant reduction of CTGF mRNA and protein, and VEGF mRNA (P < 0.01), especially in groups PRS-CTGF-siRNA1 and PRS-CTGF-siRNA4. The introduction of PRS void vector did not have these effects (P > 0.05).
The expression of CTGF siRNA mediated by PRS retrovirus vector can effectively reduce the level of CTGF and VEGF induced by TGF-beta1 in cultured HPMCs. This study may provide potential therapeutic strategies to prevent the peritoneal fibrosis.
Chinese medical journal 02/2007; 120(3):231-6. · 0.86 Impact Factor
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Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 03/2006; 31(1):146.
