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To explore the structure and function of thioredoxin glutathione reductase (TGR) from Schistosoma j aponi-cum ,the homologous model of TGR in Schistosoma j aponicum was constructed by Swiss-Pdbviewer based on sequence and structure alignment .The potential substrates binding sites of TGR were analyzed and these sites of various TGRs were also as-sessed .Our results showed that the homologous model of Schistosoma japonicum TGR based on Schistosoma mansoni TGR structure was proved to be reasonable by PROCHECK program .Analysis of binding sites showed that NADPH and GDS bind-ing sites were conservative sites and GSH binding site was a specific site for parasite .Our data suggested that inhibitors which work in NADPH and GDS binding sites of other various TGRs may also interact with TGR form Schistosoma j aponicum .GSH binding region might be one of the potential targets for design of specific inhibitors of parasite TGRs .In addition ,C-terminal of TGR plays an important role in electron transfer and may participate in the binding of the substrate .Thus compound inhibiting swing of C-terminal could effectively restrain Schistosoma j aponicum TGR activity .
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<p><b>OBJECTIVE</b>To evaluate the feasibility of monitoring clopidogrel resistance with flow cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP) phosphorylation.</p><p><b>METHODS</b>Twenty patients with coronary heart disease (CHD) and 17 healthy volunteers were examined for platelet aggregation rate and phosphorylation of VASP (calculated as platelet reactivity index, PRI) using traditional optical nephelometry and flow cytometry before and after concurrent therapy of clopidogrel and aspirin.</p><p><b>RESULTS</b>No significant differences were found in PRI between CHD group and healthy control group [(89.45∓5.22)% vs (86.58∓4.35)%] before treatment. The PRI in CHD group was significantly lowered after treatment to (67.66∓19.77)% (P<0.05). Clopidogrel resistance was found in 6 (30%) cases in CHD group by flow cytometric analysis, which showed a higher sensitivity than optical nephelometry (10%).</p><p><b>CONCLUSION</b>Flow cytometric analysis of VASP phosphorylation is a more reliable test to specifically evaluate clopidogrel resistance.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Case-Control Studies , Cell Adhesion Molecules , Chemistry , Drug Resistance , Flow Cytometry , Microfilament Proteins , Chemistry , Phosphoproteins , Chemistry , Phosphorylation , Platelet Function Tests , Ticlopidine , PharmacologyABSTRACT
Objective To investigate hemorrhagic transformation (HT) and outcomes in acute ischemic stroke.Methods The demographics,vascular risk factors,imaging and other clinical data in patients with acute ischemic acute were collected retrospectively and compared.Using the susceptibility weighted imaging (SWI) to diagnose HT,and the patients were divided into either a HT group or a non-HT group.The modified Rankin scale was used to evaluate the clinical outcomes.Multivariate logistic regression analysis was used to determine the independent risk factors for HT and poor outcome in HT patients.Results A total of 96 patients with acute ischemic stroke were enrolled and 34 of them had HT (35.4％).The age (66.21 ± 7.04 years vs.61.21 ±13.42 years; t =2.020,P=0.046) and infarct volume (3.88 ±2.20 cm3 vs.1.96 ± 1.37 cm3; t =5.67,P=0.001) in the HT group were significantly older or larger than those in the non-HT group.The proportions of hypertension (58.8％ vs.30.6％;x2 =7.228,P=0.007),diabetes (29.4％ vs.6.5％;x2 =9.293,P=0.002),atrial fibrillation (35.3％ vs.3.2％;x2=18.128,P=0.000),and cardiogenic cerebral embolism (35.3％ vs.3.2％ ; P =0.000) were significantly higher than those in the non-HT group,while the proportion of small arterial occlusive stroke was significantly lower than that in the non-HT group (38.2％ vs.62.9％ ;P =0.032).Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.168,95％ confidence interval [CI] 1.059-3.412; P =0.021),infarct volume (OR 3.461,95 ％ CI 1.317-6.270; P =0.044) and atrial fibrillation (OR 1.284,95％ CI 1.117-2.903; P =0.015) were the independent risk factors for HT.In the HT patients,age (69.46 ±7.17 years vs.64.19 ±6.31 years; t =2.248,P =0.032) in the poor outcome group was significantly older than that in the good outcome group.The proportions of hypertension (84.6％ vs.42.9％ ;x2 =781,P =0.016),diabetes (50.0％ vs.14.3％ ;x2 =6.053,P =0.014),cardiogenic cerebral embolism (61.5％ vs.19.0％ ; P =0.025) and hematoma HT (76.9％ vs.19.0％ ;x2 =11.104,P =0.001) were significantly higher than those in the good outcome group.Multivariate logistic regression analysis showed that the diabetes (OR 2.151,95％ CI 1.179-3.218; P =0.023),atrial fibrillation (OR 4.136,95％ CI1.010 to 8.413; P =0.046) and hernatoma HT (OR 2.134,95％ CI 1.219-4.452; P =0.039) were the independent risk factors for the poor outcomes of HT patients at 3 months after symptom onset.Conelusions The incidence of HT in patients with acute ischemic stroke was 35.4％.Age,infarct volume and atrial fibrillation were the independent risk factors for HT,and diabetes,atrial fibrillation and hematoma HT were the independent risk factors for the poor outcomes in HT patients at 3 months after symptom onset.
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Objective To evaluate the lung V/Q imaging in the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH).Methods Seventy-six patients (46 males,30 females,age 27-84 y) with clinically suspected CTEPH who had undergone lung V/Q imaging,CT pulmonary angiography (CTPA),pulmonary angiography (PA) and right heart cardiac catheterization were studied.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of lung V/Q imaging in detecting CTEPH were calculated and compared with those of CTPA.The x2 test was used for statistical analysis with SPSS 11.5.The distribution of involvement of segments in 47 patients with CTEPH was analyzed.Results Forty-seven patients had a final diagnosis of CTEPH and 29 had non-CTEPH etiology.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of lung V/Q imaging were 97.9％ (46/47),86.2％ (25/29),93.4％ (71/76),92.0％ (46/50) and 96.2％ (25/26),while those of CTPA were 78.7％ (37/47),93.1％ (27/29),84.2％ (64/76),94.9％ (37/39) and 73.0％ (27/37),respectively.The sensitivity (x2 =5.818,P=0.012) and negative predictive value (x2 =5.693,P =0.017) for lung V/Q imaging were significantly higher than those of CTPA.V/Q imaging could identify patients with CTEPH from those with idiopathic PAH and familial PAH based on the almost normal ventilation imaging.The lung perfusion SPECT imaging detected 585 (62.2％) of involved segments among 940 segments in 47 patients with CTEPH,with an average of 12.4 involved segments in each patient.The number of involved segments in the right lung was significantly higher than that in the left lung (36.2％ (340/940) vs 26.1％ (245/940) ; x2 =40.85,P＜0.01).Conclusions Lung V/Q imaging plays an important role in diagnosis of CTEPH and in identification of CTEPH from other types of PAH.A normal V/Q imaging can effectively exclude CTEPH.In addition,V/Q imaging can provide more diagnostic information in patients with a clinical suspicion of CTEPH who had negative results by CTPA and PA.