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1.
ObjectiveTo determine the biotic effects of angiotensin Ⅱ (Ang Ⅱ) on the migration of rat smooth muscle cells (VSMCs) and investigate the mechanisms involved in the development of vascular injury. Methods VSMCs isolated from aortic media of Wistar rats and cultured by the modified explant method were adopted. In the presence and absence of Ang Ⅱ, the expression of Ang Ⅱ receptor (ATR) and reorganization of the actin cytoskeleton and focal adhesion of VSMCs were studied by an immunocytochemistry technique and fluorocytochemistry technique. Migration assays were performed with a modified Boyden’s chamber. The effects of AT(1)R antagonist (CV- 11974), AT2R antagonist (PD123319) on the aforementioned target were studied. Results VSMCs migration was stimulated by adding Ang Ⅱ. The dynamic reorganization of actin cytoskeleton and focal adhesions may be an important mechanism by which Ang Ⅱ facilitates VSMCs motility. The expression of AT(1)R in VSMCs could be upregulated initially after treatment with Ang Ⅱ, then decreased gradually. The expression of AT(1)R was downregulated by AT(1)R antagonists. The effect of Ang Ⅱ on VSMCs migration was mediated by AT(1)R, while AT2R had no significant effect. Conclusions The dynamic reorganization of focal adhesions and the actin cytoskeleton is required for Ang Ⅱ- induced VSMCs migration. This effect is mediated by AT(1)R.  相似文献   

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Background Advanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs). Methods VSMCs were cultured and then co-incubated with AOPP (200μmol/L, 400μmol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK. Results Treatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP-1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression. Conclusions AOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect.  相似文献   

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Objective:ATP-binding cassette transporters(ABC)A1 and G1 play an important role in mediating cholesterol efflux and preventing macrophage foam cell formation.In this study,we examined the regulation of ABC transporters by high glucose in human vascular smooth muscle cells(VSMCs),the other precursor of foam cells.Methods:Incubation of human VSMCs with D-glucose(5 to 30 mM)for 1 to 7 days in the presence or absence of antioxidant and nuclear factor(NF)-κB inhibitors,the expressions of ABCA1 and ABCG1 were analyzed by real time PCR and Western blotting.Results:High glucose decreased ABCG1 mRNA and protein expression in cultured VSMCs,whereas the expression of ABCA1 was not significantly decreased.Down-regulation of ABCG1 mRNA expression by high glucose was abolished by antioxidant N-acetyl-L-cysteine(NAC)and NF-κB inhibitors,BAY 11-7085 and tosyl-phenylalanine chloromethyl-ketone(TPCK).Conclusion:High glucose suppresses the expression of ABCG1 in VSMCs,which is the possible mechanism of VSMC derived foam cell transformation.  相似文献   

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Introducing foreign gene(s) into vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) is the pre-require-ment of gene therapy for cardiovascular diseases. We have explored the use of adenoviral vectors (Adv-CMV / LacZ) to transfer LacZ gene into cultured VSMCs and ECs. Our results demonstrated that adenoviral vectors transfered foreign gene into VSMCs and ECs high-efficiently with dose-dependent response pattern. The frequencies of transfection reached 100% at the viral titer of 109 pfu / ml. Comparing the sensitivities of VSMCs and ECs to adenoviral vectors, we found that ECs were more sensitive than VSMCs, of which the frequencies of transfection in ECs reached 80% while in VSMCs only 40% for 8 hrs after transfection. In addition, the transfection of ECs and VSMCs with adenoviral vectors was partly blocked by monoclonal antibodies to Fiber and Core protein of the adenoviral capsid, but not by monoclonal antibody to Hcxon protein. It is suggested transfection of ECs and VSMCs with adenovirus  相似文献   

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Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.  相似文献   

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Objective To investigate the mechanism of a novel angiotensin n type 1 receptor-associated protein (ATRAP) interfering with angiotensin Ⅱ type 1 (AT1) receptor-mediated vascular smooth muscle cell (VSMC) growth and neointimal formation. Methods VSMCs isolated from thoracic aorta of adult Sprague-Dawley ( SD) rats were used in this study. ATRAP Cdna was subcloned into pcDNA3 vector and then transfected into VSMCs. DNA synthesis and extracellular signal-regulated kinase (ERK) and phospho-ERK expressions in VSMCs were assayed by measurement of 3H thymidine incorporation and Western blotting, respectively. Morphological changes were observed in the balloon injured artery with or without transfection of ATRAP Cdna using 12-week-old male SD rats. Results ATRAP overexpression in VSMCs inhibited angiotensin Ⅱ (Ang Ⅱ) -induced 3H thymidine incorporation 48 hours after Ang Ⅱ stimulation (P < 0.05). In VSMC, Ang Ⅱ stimulation increased the phosphorylation of ERK, which reached the peak around 60 minutes. The activation of phospho-ERK was significantly decreased by ATRAP (P < 0.05). Neointimal formation was markedly inhibited by ATRAP overexpression in injuried arteries. Conclusions The AT1 receptor-derived activation of ERK plays an essential role in Ang Ⅱ-induced VSMC growth. The growth inhibitory effects of ATRAP might be due to interfering with AT1 receptor-mediated activation of ERK in VSMC growth and neointimal formation.  相似文献   

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Lipoma preferred partner(LPP) has been identified as a protein which is highly selective for smooth muscle progenitor cells(SMPCs) and regulates differentiation and migration of SMPCs,but mechanisms of LPP expression are not elucidated clearly.The aim of the present study was to discuss the mechanisms by which LPP expression is regulated in the differentiation and migration of SMPCs induced by TGF-β1.It was found that TGF-β1 could significantly increase the expression of LPP,smooth muscle α-actin,smooth muscle myosin heavy chain(SM-MHC),and smoothelin in SMPCs.Moreover,inactivation of Rho kinase(ROK) with ROK inhibitors significantly inhibited LPP mRNA expression in TGF-β1-treated SMPCs and mouse aortic smooth muscle cells(MAoSMCs).At the same time,LPP silencing with short interfering RNA significantly decreased SMPCs migration.In conclusion,LPP appears to be a ROK-dependant SMPCs differentiation marker that plays a role in regulating SMPCs migration.  相似文献   

11.
Objective To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.Methods Five hundred and thirty‐nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved.The genotypes of GSTM1,GSTT1,GSTP1,GSTM3,and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis.The observed polymorphisms were analyzed by Chi‐square and Hardy‐Weinberg equilibrium...  相似文献   

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Objective A highly sensitive and rapid high‐performance liquid chromatography method with pre‐column derivatization with 4‐fluoro‐7‐nitrobenzofurazan was developed for determination of taurine in biological samples,including plasma,brain,and liver.Methods The optimum derivatization reaction temperature was 70℃,and at this temperature the reaction was complete within 3 min.The derivatized taurine was separated using phosphate buffer (0.02 mol/L,pH 6.0):acetonitrile (84:16,v/v) as the mobile phase at a flow r...  相似文献   

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Objective To break immune tolerance to prion (PrP) proteins using DNA vaccines.Methods Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector:PrP‐WT expressing wild‐type PrP,Ubiq‐PrP expressing PrP fused to ubiquitin,PrP‐LII expressing PrP fused to the lysosomal integral membrane protein type II lysosome‐targeting signal,and PrP‐ER expressing PrP locating the ER.Using a prime‐boost strategy,three‐doses of DNA vaccine were injected intramuscularly into Balb/c mice,fol...  相似文献   

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Background

A sizeable portion of psychiatric ward beds in military hospitals is occupied by patients with psychoactive substance abuse and especially by alcohol-dependence syndrome (ADS) cases. Though there have been significant advances in the diagnosis and management of these cases, not much of work has been done in our set up for the evaluation of their cognitive impairment and its response to treatment.

Methods

Neuropsychological evaluation of 100 cases of freshly diagnosed ADS was done by using postgraduate battery of brain dysfunction (PGI-BBD). The findings were compared with controls. They were detoxified, treated and after four weeks were re-evaluated and the findings were analysed.

Results

There was significant impairment in all parameters of cognition. All of them showed improvement with treatment but after four weeks, the impairment persisted to significant level in some parameters.

Conclusion

Alcohol-dependence syndrome cases have significant cognitive impairment but improve with detoxification, multivitamin supplement and abstinence. This aspect has to be kept in mind while deploying them in sensitive appointments.  相似文献   

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Objective To compare the bacterioplankton communities in streams exposed to pollution of different types. Methods The bacterioplankton communities in three selected heavily polluted streams were investigated by using terminal‐restriction fragment length polymorphism (T‐RFLP) analysis in combination with 16S rRNA gene clone library analysis. Results Both T‐RFLP and 16S rRNA gene clone library revealed a great difference in bacterioplankton community composition in the different streams. Conclusion This work ...  相似文献   

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Objective

Surgical Process Models (SPMs) are models of surgical interventions. The objectives of this study are to validate acquisition methods for Surgical Process Models and to assess the performance of different observer populations.

Design

The study examined 180 SPM of simulated Functional Endoscopic Sinus Surgeries (FESS), recorded with observation software. About 150,000 single measurements in total were analyzed.

Measurements

Validation metrics were used for assessing the granularity, content accuracy, and temporal accuracy of structures of SPMs.

Results

Differences between live observations and video observations are not statistically significant. Observations performed by subjects with medical backgrounds gave better results than observations performed by subjects with technical backgrounds. Granularity was reconstructed correctly by 90%, content by 91%, and the mean temporal accuracy was 1.8 s.

Conclusion

The study shows the validity of video as well as live observations for modeling Surgical Process Models. For routine use, the authors recommend live observations due to their flexibility and effectiveness. If high precision is needed or the SPM parameters are altered during the study, video observations are the preferable approach.  相似文献   

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Objective

This study evaluated the effect of a Computerized Physician Order Entry system with basic Clinical Decision Support (CPOE/CDSS) on the incidence of medication errors (MEs) and preventable adverse drug events (pADEs).

Design

Interrupted time-series design.

Measurements

The primary outcome measurements comprised the percentage of medication orders with one or more MEs and the percentage of patients with one or more pADEs.

Results

Pre-implementation, the mean percentage of medication orders containing at least one ME was 55%, whereas this became 17% post-implementation. The introduction of CPOE/CDSS has led to a significant immediate absolute reduction of 40.3% (95% CI: −45.13%; −35.48%) in medication orders with one or more errors.Pre-implementation, the mean percentage of admitted patients experiencing at least one pADE was 15.5%, as opposed to 7.3% post-implementation. However, this decrease could not be attributed to the introduction of CPOE/CDSS: taking into consideration the interrupted time-series design, the immediate change was not significant (−0.42%, 95% CI: −15.52%; 14.68%) because of the observed underlying negative trend during the pre-CPOE period of −4.04% [95% CI: −7.70%; −0.38%] per month.

Conclusions

This study has shown that CPOE/CDSS reduces the incidence of medication errors. However, a direct effect on actual patient harm (pADEs) was not demonstrated.  相似文献   

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Background

Angiogenesis is critical for the growth of colorectal carcinoma (CRC). Vascular endothelial growth factor is the most important angiogenic growth factor.

Method

Fifty cases of CRC operated at INHS Asvini were studied by using immunohistochemical labelling of the tumours by using CD34, p53, and vascular endothelial growth factor (VEGF).

Results

Out of the 50 cases, 31 (62%) were positive for p53; of which 80.7% showed high expression. Significant staining (> 20% tumour cells showing positivity) was seen in 33 patients (66%), while 34% were negative. Of the 33 positive cases, 57.58% showed high-grade VEGF positivity.

Conclusion

Vascular endothelial growth factor correlated significantly with the stage and grade of disease. Intra tumours microvessel density as calculated from CD34 expression increased with the stage and grade of the CRC.  相似文献   

19.

Objective

To facilitate patient handoffs between physicians, the computerized patient handoff tool (PHT) extracts information from the electronic health record to populate a form that is printed and given to the cross-cover physician. Objectives were to: (1) evaluate the rate at which data elements of interest were extracted from the electronic health record into the PHT, (2) assess the frequency for needing information beyond that contained in the PHT and where obtained, (3) assess physician's perceptions of the PHT, (4) identify opportunities for improvement.

Design

Observational study.

Measurements

This multi-method study included content coding of PHT forms, end of shift surveys of cross-cover resident physicians, and semi-structured interviews to identify opportunities for improvement. Thirty-five of 42 internal medicine resident physicians participated. Measures included: 1264 PHT forms coded for type of information, 63 end-of-shift surveys of cross-cover residents (residents could participate 2 times), and 18 semi-structured interviews.

Results

For objective 1, patient identifiers and medications were reliably extracted (>98%). Other types of information—allergies and code status—were more variable (<50%). For objective 2, nearly a quarter of respondents required information from physician notes not available in the PHT. For objective 3, respondents found that the PHT supported handoffs but indicated that it often excluded the assessment and plan. For objective 4, residents suggested including treatment plans.

Conclusions

The PHT reliably extracts information from the electronic health record. Respondents found the PHT to be suitable, although opportunities for improvement were identified.  相似文献   

20.

Background

Polymethylmethacrylate (PMMA) is the most common material used to fabricate interim fixed partial denture (FPD). Several attempts have been made to improve fracture strength of this material with various methods of reinforcement, but its effect on the fracture resistance of interim FPD was not evaluated.

Method

The study was designed in two stages. In the first stage various methods of reinforcement (glass fibre, polyethylene, combination of glass and polyethylene, and stainless steel) for interim FPD of PMMA were used and its effect on the fracture resistance of interim FPD was evaluated by three point bending test using universal testing machine. In the second stage, fibres which showed the highest fracture resistance value was used to ascertain the most appropriate site of placement for reinforcing interim FPD. Comparisons were made with analysis of variance.

Results

Stainless steel and glass fibres showed significantly higher fracture resistance value than polyethylene alone or mixed with glass fibres (P < 0.001). Fibre placement in the occlusal third region of the pontic resulted in higher fracture resistance than the other locations (P < 0.05).

Conclusion

There was a definite improvement in the fracture resistance after reinforcement with fibres and stainless steel. The occlusal third region of the pontic is the most appropriate site of placement for reinforcement in interim FPD.  相似文献   

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