Cryptotanshinone (CPT), a lipid soluble active compound in Salvia miltiorrhiza, has a significant inhibitory effect on multiple malignant tumors, e. g. chronic myeloid leukemia (CML) cells and can effectively enhance imatinib's chemotherapeutic effect. However, its functional molecular mechanism remained unclear. In this experiment, the authors conducted a systematic study on the effect of CPT on the imatinib sensitivity and P-glycoprotein (P-gp) expression in CML cells by using CML cells K562 and imatinib persister K562-R. The MTT assays were performed to determine CPT's impact on the inhibitory effect of imatinib. Annexin V-FITC/PI staining analysis was used to detect the changes in the cell apoptosis rate. The active changes in apoptosis regulatory proteins Caspase-3, Caspase-9 and PARP were determined by Western blot. After the cells were pretreated with the gradient concentration of CPT, the expression of P-gp was analyzed by Western blot and flow cytometry. The changes in intracellular concentrations of imatinib were determined by HPLC analysis. The results indicated that the pretreatment with CPT significantly increased the proliferation inhibiting and apoptosis inducing effects of imatinib on K562 and K562-R cells as well as the degradation product expression of pro-apoptotic proteins Caspase-3, Caspase-9 and PARP, with a significant difference with the control group (P < 0.01). However, CPT showed no impact on the P-gp expression in CML cells and the intracellular concentrations of imatinib. In summary, the findings suggested that CPT enhanced the sensitivity of CML cells to imatinib. Its mechanism is not dependent on the inhibition in P-gp expression and the increase in intracellular drug concentration.
ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; genetics ; metabolism ; Caspase 9 ; genetics ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Imatinib Mesylate ; pharmacology ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; physiopathology ; Phenanthrenes ; pharmacology

OBJECTIVETo estimate the feasibility of 16-multidetector spiral computed tomography (16-MDCT) on detecting coronary plaques in comparison with intravascular ultrasound (IVUS).

METHODSSixty-eight patients suspected of coronary heart diseases were examined by 16-MDCT, quantitative coronary angiography (QCA) and IVUS. Coronary stenosis was defined as lumen diameter reduction (DS) >or= 50%. Hounsfield units (HU) were used to determine different types of plaques: soft plaque (or= 120 HU).

RESULTSCompared to QCA, the sensitivity and the specificity for patients with DS >or= 50% were 91.8% (112/122) and 97.8% (556/568) respectively, the positive and negative predictive value were 90.3% (112/124) and 98.2% (556/566) respectively. In 96 plaques evaluated both by 16-MDCT and IVUS, 20 and 21 soft plaques, 37 and 36 fibrous plaques, 39 and 38 calcified plaques were identified by 16-MDCT and IVUS respectively. HU value of soft (11 +/- 36), fibrous (83 +/- 20), and calcified (292 +/- 80) plaques were significantly different (P < 0.05).

CONCLUSIONSNoninvasive 16-MDCT could correctly estimate coronary stenosis and coronary plaques compositions.

Aged ; Atherosclerosis ; diagnostic imaging ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Tomography, Spiral Computed ; methods ; Ultrasonography, Interventional

OBJECTIVETo develop a method for the determination of salvianolic acid B and paeoniflorin in Shuangdan granules.

METHODThe chromatographic separation was performed on a Zorbax SB C18 column with a linear gradient elution of phosphoric acid-water (0.05:100) and phosphoric acid-acetonitrile-methanol (0.05:4:96) was used. The flow rate was 1 mL x min(-1) and column temperature was set at 25 degrees C. The UV detection wavelength was set at 230 nm.

RESULTThe linear ranger was of 0.710-22.7 microg for salvianolic acid B and 0.103-3.30 microg for paeoniflorin. Three batches of Shuangdan granules were analyzed, and the content of salvianolic acid B ranged from 6.46-11.6 mg x g(-1) and paeoniflorin ranged from 1.44-1.78 mg x g(-1).

CONCLUSIONThe method was accurate, reproducible, reliable, and could be used for quantitative control of Shuangdan granules.

Benzoates ; analysis ; Benzofurans ; analysis ; Bridged-Ring Compounds ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Glucosides ; analysis ; Monoterpenes ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry

E2 gene of classical swine fever virus (CSFV) was cloned into secretory pPIC9K Pichia pastoris expression vector. After being linearized by digestion, the vector was transformed into Pichia pastoris by electroporation to integrate with the genome, the transformants with high copies were screened by G418 and were induced to express with methonal. The results of SDS-PAGE and Western blot demonstrated that the supernatant of the induced P. pastoris culture contained protein E2. The results of the study on the immunological activity indicated that the protein E2 expressed in P. pastoris can elicit animal bodies to produce antibodies against protein E2.
Animals ; Antibodies, Viral ; immunology ; Antigens, Viral ; genetics ; immunology ; Classical swine fever virus ; genetics ; immunology ; Cloning, Molecular ; Gene Expression ; Pichia ; Rabbits ; Swine ; Viral Envelope Proteins ; genetics ; immunology

OBJECTIVETo explore the possibility of clinical evaluation of cardiac function by CHM T3002 non-invasive hemodynamic monitor.

METHODSA total of 26 patients admitted to Zhongshan Hospital in Shanghai were enrolled, including 11 cardiac insufficiency patients and 15 control. Each subject was tested by non-invasive cardiac hemodynamic monitor immediately after echocardiography. Linear regression analysis and Bland-Altman consistency analysis were used in the analysis of relevance and consistency between two different methods.

RESULTSLinear correlation was shown on LVEF, SV, SVI, CO, CI, EDV, LVET and PEP/LVET, but not on PEP, between the two methods. Moreover, the consistency of the two methods was highly confirmed on LVEF and LVET, less on SV, SVI, CO, CI and EDV, while awfully weak on PEP and PEP/LVET.

CONCLUSIONCHM T3002 non-invasive hemodynamic monitor may be useful in assessing patients' cardiac function, however, it can not replace cardiac echocardiography.

Adult ; Aged ; Case-Control Studies ; Echocardiography ; instrumentation ; Equipment Design ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; instrumentation

OBJECTIVETo study cardiac troponin T (TNNT2) gene mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and analyze the correlation between the genotype and phenotype.

METHODSNinety-five unrelated Chinese patients with HCM and 120 control individuals were screened for TNNT2 gene mutations. Seven exons (8, 9, 10, 11, 14, 15, and 16) in the functional regions of TNNT2 gene were amplified using PCR and the products were sequenced. The patients with positive results underwent further family screening.

RESULTS AND CONCLUSIONThis study did not find any HCM-caused mutations in TNNT2 gene, a result different from the reported rates of TNNT2 gene mutation ranging from 10% to 20% in other nations, suggesting that TNNT2 gene is not a susceptible gene for HCM in Chinese population.

Asian Continental Ancestry Group ; genetics ; Cardiomyopathy, Hypertrophic ; genetics ; Case-Control Studies ; Humans ; Mutation ; Troponin T ; genetics

OBJECTIVETo study the changes of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in the autologous vein grafts and vein graft atherosclerotic lesions.

METHODSThirty New Zealand white rabbits were randomly assigned to normal control group (rabbits fed with normal diet, n = 10), vein graft group (autologous external jugular vein grafting to common carotid artery and fed with normal diet, n = 10) or vein graft plus high-lipid diet group (autologous vein graft and fed with high-lipid diet, n = 10) for 12 weeks. LOX-1 expressions in the grafts were examined by immunohistochemistry and semi-quantitative reverse transcription-PCR. The relationships between serum total cholesterol level, intimal thickness and LOX-1 expression were also investigated.

RESULTSLOX-1 expression was low in the endothelium of external jugular veins in the normal control group and significantly increased in the endothelium and neointima of vein grafts in the vein graft group (0.31 +/- 0.14 vs. 0.09 +/- 0.04, P < 0.01) and which was further increased in the endothelium and atherosclerotic lesions in the vein graft plus high-lipid diet group (0.93 +/- 0.34 vs. 0.31 +/- 0.14, P < 0.01). LOX-1 expression in the atherosclerotic lesions was located both in endothelial cells and foam cells and the expression was most prominent in endothelial cells. LOX-1 expression and intimal thickness were positively related to serum total cholesterol level (P = 0.00 and 0.02) and the partial correlation coefficient was 0.78 and 0.42, respectively.

CONCLUSIONSLOX-1 expression is increased in endothelium and neointima of autologous vein grafts of rabbits. Hypercholesterolemia upregulates LOX-1 expression in vein graft atherosclerosis. Thus, LOX-1 might play an important role in the pathogenesis of vein graft atherosclerosis.

Animals ; Atherosclerosis ; metabolism ; pathology ; Disease Models, Animal ; Graft Occlusion, Vascular ; metabolism ; pathology ; Lipoproteins, LDL ; blood ; Male ; Rabbits ; Scavenger Receptors, Class E ; metabolism ; Transplantation, Autologous ; Veins ; transplantation

Objective To investigate the differences of blood glycosylated hemoglobin (HbA1c) levels between the patients with acute cerebral infarction and healthy controls, and explore the relation between HbA1c level and both neurological deficits scores and imaging of lesions in number. Methods One hundred and eighty-six patients with acute cerebral infarction within 1 week were performed neurological deficits scales after the admission; the HbA1c level was measured within 24 h admission; brain MRI scan was performed on these patients 48 h after onset or stabilization. Glucose tolerance test was taken at the rehabilitation of infarction (except for having a clear history of diabetes before). At the same time, 160 healthy controls were checked on the level of HbA1c and taken the glucose tolerance test. The differences of blood HbA1c levels between the patients with acute cerebral infarction and healthy controls were investigated; and the relation between HbA1c level and both neurological deficits scores and imaging of lesions in number was explored. Results The HbA1c level in patients with acute cerebral infarction (6.982%±1.803%) was significantly higher than that in the controls (5.128%±0.592%, P<0.05). The level of HbA1c in patients with cerebral infarction and the neurological deficits scores were positively correlated (r=0.760, P<0.05). The level of HbA1c in patients with 2 lesions (6.635%±0.427%) was obviously higher than that in patients with 1 lesion (5.803%±0.307%, P<0.05); The level of HbA1c in patients with 3 or more lesions (8.571%±0.519%) was obviously higher than that in patients with 1 or 2 lesions (P<0.05). Conclusion Diabetes is a major risk factor for cerebral infarction. High HbA1c level might cause a series of cerebrovascular diseases, thus it is an important factor in the happening of cerebral infarction and HbA1c level is an important indicator of the early assessment of the severity of the diseases. The incidence of cerebral infarction can be decreased by controlling hyperglycaemia, lowering the HbA1c levels.

BACKGROUNDInvasive intravascular ultrasound (IVUS) is current diagnostic standard for myocardial bridging (MB). Non-invasive multislice computerized tomography coronary angiography (MSCT) technique has provided a good anatomical view of the tunnel artery now.

METHODSA total of 51 consecutive patients with atypical or typical angina scheduled for IVUS were enrolled in this study and MSCT was performed 7 days before IVUS. Coronary imaging was quantified using IVUS and MSCT. Four main vessels (left main artery (LMA), left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA)) were examined.

RESULTSForty-one out of 51 (80%) patients received metaprolol (25 mg) before the MSCT scan and 25 of them were current beta-blocker users. The mean heart rate was (64 +/- 3) beats per minute. A total of 51 patients underwent IVUS examination (30 with MB and 21 without MB) were chosen for this study. Twenty-eight out of 30 MB cases were correctly diagnosed by MSCT and 2 patients with MB were not detected. Comparison with IVUS, the sensitivity of detection by MSCT was 93%, specificity was 100%. The lumen diameter of the tunnel artery derived from MSCT and IVUS significantly decreased from (2.9 +/- 0.3) mm to (2.4 +/- 0.4) mm (P < 0.001) and from (3.3 +/- 0.3) mm to (2.6 +/- 0.5) mm (P < 0.001), respectively. Minimal and maximal diameters of MB derived from MSCT were significantly smaller than those from IVUS ((2.4 +/- 0.4) mm vs (2.6 +/- 0.5) mm, P < 0.05 and (2.9 +/- 0.3) mm vs (3.3 +/- 0.3) mm, P < 0.05), respectively.

CONCLUSIONSMSCT offers a reliable non-invasive method for MB in LAD and atherosclerosis diagnosis with diagnostic accuracy comparable with invasive IVUS.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myocardial Bridging ; diagnostic imaging ; Tomography, Spiral Computed ; methods ; Ultrasonography, Interventional ; methods

OBJECTIVETo investigate the effect of coronary microemboliation (CME) on coronary microvascular injury and myocardial endothelin-1 (ET-1) level.

METHODSCME was induced in 10 miniswines by selective infusion of microspheres (45 microm) into left anterior descending artery (LAD). The ET-1 level in coronary sinus was measured with radioimmunoassay. The microvascular integrity indicator CFR was measured by Doppler flow wire in LAD at baseline and after infusion of microspheres.

RESULTCompared to the baseline, CFR decreased significantly with different doses of microspheres. ET-1 level increased significantly with doses of 5 x 10(4) and peaked with 10 x 10(4), and progressively decreased from doses of 12 x 10(4) to 15 x 10(4) microspheres. There was negative correlation between ET-1 and CFR (r=-0.31, P=0.02).

CONCLUSIONThe extent of microvascular injury is not linearly related to the extent of microembolization, but it is closely associated with myocardial ET-1 level.

Animals ; Coronary Vessels ; pathology ; Disease Models, Animal ; Embolism ; Endothelin-1 ; blood ; Female ; Male ; Myocardial Infarction ; blood ; pathology ; Swine ; Swine, Miniature