BACKGROUNDStatins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.

METHODSForty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography.

RESULTSAfter treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P < 0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P < 0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P < 0.05) compared with levels measured during the 4th week.

CONCLUSIONSCoronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Adult ; Aged ; Azetidines ; administration & dosage ; Cholesterol ; metabolism ; Cholesterol, LDL ; blood ; Coronary Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; administration & dosage

BACKGROUNDVasoactive factors have been reported to correlate with vulnerable plaque and acute coronary syndrome (ACS). This study aimed to investigate the relationship between vasoactive factors and plaque morphology in patients suffering from non-ST-segment elevated ACS.

METHODSFrom April 2007 to April 2009, 124 consecutive patients suffering from non-ST-segment elevated ACS who had received coronary angiography (CAG) and intravascular ultrasound (IVUS) in the People's Liberation Army General Hospital and Beijing Anzhen Hospital were enrolled in this study. Three serum vasoactive factors, plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1), placental growth factor (PLGF) and interleukin-18 (IL-18), were measured by enzyme-linked-immunosorbent serologic assay of the patients. The levels of vasoactive factors were compared between vulnerable plaque group and stable plaque group, and between unstable angina pectoris (UAP) group and non-ST-segment elevation acute myocardial infarction (NSTE-AMI) group. The relationship between the plaque morphology and levels of vasoactive factors was analyzed.

RESULTSThe levels of vasoactive factors were similar between the UAP group (69 patients) and NSTE-AMI group (55 patients). The levels of sFlt-1 and PLGF in the vulnerable plaque group were significantly higher than those in the stable plaque group. The level of IL-18 was correlated positively with plaque morphology. Multivariate Logistic regression analysis showed that the level of PLGF was an independent risk factor for vulnerable plaque (OR=2.115, 95% CI 1.415-5.758, P=0.018). Using the ROC curve, PLGF was a significant factor for the diagnosis of vulnerable plaque (the diagnostic point was 26.3 ng/L, the proportion of square area under the ROC curve was 0.799, 95%CI 0.758-0.839, P<0.001; the sensitivity of PLGF under the ROC curve was 86%, and the specificity 63%).

CONCLUSIONBoth IL-18 and PLGF are biomarkers for vulnerable plaques and helpful to predict vulnerable plaque.

Acute Coronary Syndrome ; blood ; diagnostic imaging ; Aged ; Angina Pectoris ; blood ; diagnostic imaging ; Angina, Unstable ; blood ; diagnostic imaging ; Coronary Angiography ; Female ; Humans ; Interleukin-18 ; blood ; Male ; Middle Aged ; Placenta Growth Factor ; Pregnancy Proteins ; blood ; Ultrasonography, Interventional ; Vascular Endothelial Growth Factor Receptor-1 ; blood

OBJECTIVETo study the expressions of VEGF/VEGFRs and activation of STATs in ovarian epithelial carcinoma, and to elucidate direct effect of VEGF on ovarian carcinoma cells.

METHODSTissue samples from 42 women with primary ovarian epithelial carcinoma (OVCA), 29 with begnin ovarian tumor (OVBT) and 11 with normal ovarian tissue (NOV) were collected. LSAB immunohistochemical staining was used to determine the expression of VEGF, VEGFR1, VEGFR2 and activated STATS (P-STAT1, P-STAT3, P-STAT5, P-STAT6) proteins.

RESULTS(1) Semi-quantitative scoring showed that VEGF expression in OVCA was significantly higher than that in OVBT and NOV (P < 0.01). Expressions of VEGFR1 and VEGFR2 were significantly elevated in OVCA, including tumor cells and stromal vascular endothelial cells (P < 0.01, compared with OVBT and NOV). There was no difference in VEGFRs expressions between OVBT and NOV. (2) In OVCA, tumor cells and endothelial cells expressed P-STAT3 and P-STAT5 at significantly higher levels than those in OVBT and NOV (P = 0.000). The staining of P-STAT1 and P-STAT6 was weak with no significant differences among OVCA, OVBT and NOV. (3) Expressions of VEGFR1 and VEGFR2 in endothelial cells were significantly correlated with P-STAT5 and P-STAT3, respectively (P = 0.006 and 0.001). In cancer cells, VEGF, VEGFR1 and VEGFR2 were all significantly correlated with P-STAT3 and P-STAT5 (P = 0.000), but not with P-STAT1 or P-STAT6.

CONCLUSIONVEGF affects ovarian carcinoma cells via VEGFRs, and STATs probably participate in intracellular signaling of VEGF.

Adult ; Aged ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Endothelial Cells ; metabolism ; Female ; Humans ; Middle Aged ; Milk Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Ovary ; metabolism ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Signal Transduction ; Trans-Activators ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

OBJECTIVETo investigate the anti atherosclerosis effect and related mechanisms of total flavone of radix puerariae (TFRP) on atherosclerotic plaques in apoE gene deficiency (apoE-/-) mice.

METHODSapoE-/- mice were treated with saline, TFRP 15 mg . kg(-1). d(-1) or TFRP 85 mg . kg-1. d-1 (n = 8 each group) respectively per gavage for 12 weeks. The apoptotic cells in atherosclerotic plaques were then detected by TUNEL analysis, transmission electron microscope (TEM). The expression of CD-68, SMA and Caspase-3 were determined by immunochemical methods.

RESULTSEarly macrophage apoptosis signs were observed under TEM, TUNEL-positive and CD-68 positive cells were found in lipid cores of atherosclerotic plaques. TFRP significantly reduced the number of apoptotic cells in a dose-dependent manner [(0.38 +/- 0.17)%, (1.95 +/- 1.02)%, (10.50 +/- 5.89)%, respectively, P < 0.01] in atherosclerotic plaques. TFRP treatment also significantly reduced the immune expression of Caspase-3 protein in a dose-dependent manner.

CONCLUSIONTFRP significantly attenuated the development of advanced atherosclerotic plaques in a dose-dependent manner which might related to down-regulated expression of Caspase-3 protein and reduced macrophage apoptotic cells in atherosclerotic plaques post TFRP treatment.

Animals ; Apolipoproteins E ; genetics ; Apoptosis ; drug effects ; Atherosclerosis ; genetics ; pathology ; Caspase 3 ; genetics ; metabolism ; Disease Models, Animal ; Flavones ; pharmacology ; In Situ Nick-End Labeling ; Macrophages ; cytology ; Male ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular ; cytology ; Pueraria ; chemistry

OBJECTIVETo develop an alternative method for assessment of gene delivery systems in vivo.

METHODSMouse primary spleen lymphocytes were genetically modified in vitro by a retroviral vector harboring a Gaussia luciferase (Gluc) expression cassette. After implantation of these cells into recipient mice, the expression of Gluc was detected in whole blood or plasma collected.

RESULTSAs little as 10 muL whole blood drawn from the recipient mice could guarantee prompt reading of Gluc activity with a luminometer. And the reading was found in good correlation with the number of genetically modified spleen lymphocytes implanted to the mice.

CONCLUSIONSGluc may be useful as an in vivo reporter for gene therapy researches, and Gluc blood assay could provide an alternative method for assessment of gene delivery systems in vivo.

Animals ; Arecaceae ; enzymology ; Cell Line ; Gene Transfer Techniques ; Genes, Reporter ; Humans ; Luciferases ; genetics ; Mice

OBJECTIVETo investigate bone defect healing by true bone ceramic complex carrying core binding factor a1 (Cbfa1) gene modified rabbit skin fibroblasts.

METHODSTransfect rabbit skin fibroblasts (RSF) with both eukaryotic expression vector pSG5 which could express Cbfa1 gene and pSG5. After being cultured for 48 h, the transfected RSF were seeded into true bone ceramic (TBC) of 2 cm in length and 4 mm in diameter to construct pSG5-Cbfa1/RSF/TBC complex and pSG5/RSF/TBC complex. Forty-eight bone defect model rabbits were randomized into four groups, each has 6 rabbits (12 radius), due to different treatment. group I: with pSG5-Cbfa1/RSF/TBC complex, group II: with pSG5/RSF/TBC complex, group III: with TBC, Group IV: empty control. After being seeded and cultured for about 24 h the complexes were implanted into 2 cm long bone defects in the middle of bilateral radius of rabbits. The radius were inspected by X-ray and then the specimens were collected at the end of the fourth and twelfth weeks after operation. Then, the specimens were decalcified and histologically investigated with Hematoxylin eosin staining and Masson staining methods. Newly synthesized trabecular bone was inspected by image analysis system and the strength of bone defect area treated with graft-implantation was tested with biomechanical method-three point bending test.

RESULTSIn group I, trabecular bone was actively synthesized to generate a great amount of trabecular bone and osteon. Preliminary union and bone defect healing were completed with good biomechanical characteristics. There were no newly synthesized trabecular in the other three groups, and bone defect healing were not discovered. The amount of newly synthesized trabecular bone and the results of biomechanical testing differed significantly between group I and the other three (P < 0.01). The efficacy of group I was significantly better than that of the other three groups.

CONCLUSIONTrue bone ceramic complex composed with Cbfa1 gene modified rabbit skin fibroblasts can effectively heal bone defect in rabbits.

Animals ; Bone Regeneration ; Bone Substitutes ; Bone Transplantation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit ; genetics ; Disease Models, Animal ; Fibroblasts ; cytology ; metabolism ; Plasmids ; genetics ; Rabbits ; Radius ; injuries ; physiopathology ; surgery ; Random Allocation ; Skin ; cytology ; Tissue Engineering ; methods ; Transfection

BACKGROUNDThe long term prognosis of unprotected left main coronary artery (LMCA) stenting is controversial. This study was conducted to evaluate the immediate and long term outcomes of LMCA stenting in Chinese patients and to determine which factors affect the outcomes.

METHODSFrom May 1997 to March 2003, 224 patients in 23 hospitals underwent elective unprotected LMCA stenting with bare metal stents. Their clinical records were analysed to ascertain immediate and long term outcomes of LMCA stenting as well as factors influencing the prognosis.

RESULTSStents were implanted into LMCA successfully in 223 cases (99.6 %). One death (0.5%) and one case of non-Q wave nonfatal myocardial infarction (MI) occurred in hospital. The mean follow-up time was (15.6 +/- 12.3) months. Cardiac death developed in 10 cases (4.5%), noncardiac death in 2 cases (0.9%), nonfatal MI in 4 cases (1.8%), target lesion revascularization (TLR) of LMCA in 26 cases (11.7%) and TLR of nonLMCA in 37 cases (16.5%). Univariate analysis showed that cardiac death correlated with left ventricular ejection fraction (LVEF < 40%), female gender and LMCA combined with multivessel disease; that major adverse cardiac events (MACE) correlated with LVEF < 40%, bifurcation lesion and incomplete revascularization. Logistic regression analysis revealed that LVEF < 40% and female gender were independent predictors of cardiac death and MACE. Follow-up angiography was performed in 102 cases (45.7%). The restenosis rate was 31.4%.

CONCLUSIONSLong-term outcomes of stenting for selected patients with unprotected LMCA stenosis is acceptable. It should be performed in inoperable or low risk patients with LVEF > or = 40% and isolated LMCA disease or LMCA combined with multivessel diseases in whom complete revascularization can be obtained.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Disease ; therapy ; Coronary Restenosis ; etiology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stents ; adverse effects ; Treatment Outcome

BACKGROUNDAvailable drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.

METHODSA prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length ≤ 40 mm, reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis.

RESULTSAngiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25 ± 0.33) mm vs. (0.57 ± 0.55) mm, diff (95%CI) -0.23 (-0.32, -0.14), P < 0.0001; in-segment (0.25 ± 0.33) mm vs. (0.42 ± 0.55) mm, diff (95%CI) -0.13 (-0.23, -0.02), P = 0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P = 0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P = 0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P = 0.1630).

CONCLUSIONSTIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Artery Disease ; drug therapy ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Polymers ; chemistry ; Sirolimus ; analogs & derivatives ; therapeutic use ; Treatment Outcome

OBJECTIVETo observe the expression pattern of bone morphogenetic protein receptor IA (BMPR IA) in rats after contusive spinal cord injury.

METHODSThe expressions of BMPR IA, IB, and II were detected by immunochemistry in the spinal cord of normal adult rats, and the expression of BMPR IA was detected in the infinite horizons impactor model at 1, 3, 7, 14, 30, and 60 days after spinal cord injury.

RESULTSIn the spinal cord of normal adult rats, BMPR IA and II were expressed predominantly in the oligodentrocytes and neurons in the grey matter, and also in some astrocytes and numerous microglia cells. Only a low level of BMPR IB expression was detected in the neurons of the grey matter. After spinal cord injury, the expression of BMP IA markedly increased with sustained strong expression in the astrocytes till one month after the injury; its expression was also increased obviously in the microglia cells activated by the injury.

CONCLUSIONThe expression of BMPR IA increases significantly in the astrocytes and activated microglia cells in rats after contusive spinal cord injury, suggesting the involvement of BMP signaling pathway in the physiological and pathological role of glia cells.

Animals ; Astrocytes ; metabolism ; Bone Morphogenetic Protein Receptors, Type I ; metabolism ; Female ; Microglia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism