To investigate the effects of icariin (ICA) on angiotensin Ⅱ(Ang Ⅱ)-induced injury in human umbilical vein endothelial cells line (ECV-304). The ECV-304 cells were cultured in vitro. After 24 h incubating with...To investigate the effects of icariin (ICA) on angiotensin Ⅱ(Ang Ⅱ)-induced injury in human umbilical vein endothelial cells line (ECV-304). The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability (MTT method), Lactate dehydrogenase (LDH) release and Nitric oxide (NO) production in the medium, the capacity of scavenging superoxide anion radicals (O2^-) and hydroxyl radicals (.OH) were measured. The activities of superoxide dismutase (SOD), total nitric oxide synthase (T-NOS), inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals ( O2^- ) and hydroxyl radicals(.OH), and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells (ECV-304) from Ang II-induced injury.展开更多
Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin w...Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.展开更多
Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabb...Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.展开更多
AIM: To study the effects of endotoxin on portal hemodynamic of normal and noncirrhotic portal hypertensive rats. METHODS: Normal rats were intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of lip...AIM: To study the effects of endotoxin on portal hemodynamic of normal and noncirrhotic portal hypertensive rats. METHODS: Normal rats were intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of lipopolysaccharide(LPS) respectively, portal vein ligation(PVL) and intrahepatic portal occlusion (IPO) rats as well as sham-operated rats were treated with an intraperitoneal injection of 1.0mg.kg(-1) of LPS, the portal vein pressure(PVP), portal venous flow(PVF), inferior vena cava pressure(IVCP) and portal vein resistance(PVR) were detected 4 hours after injection. RESULTS: PVF of the 5 groups of rats accepting intraperitoneal injection of LPS were increased from 14.0 to 18.0, 22.2, 26.2, 34.8, 39.6, 38.8 mL.min(-1) 4 hours after injection of LPS(P【0.01). PVP of the 4 groups of rats accepting more than 0.1mg/kg.b.w of LPS was increased from 1.04 to 1.25, 1.50, 1.80, 1.95, 2.05 kPa(P【0.01). The increments of PVF and PVP were in a dose-dependent manner of LPS. PVR of the 5 groups of rats was decreased from 51 to 42,44,48,45,44,47 kPa.min.L(-1) (P【0.05) and no dose-dependent manner was observed. PVF of PVL, IPO and sham-operated rats increased from 22.6 to 32.8, 22.0 to 28.0, 14.0 to 34.8 mL.min(-1) (P【0.01), and PVP increased from 1.86 to 2.24, 1.74 to 1.95, 1.04 to 1.80 kPa(P【0.01), PVR decreased from 71 to 61, 67 to 61, 52 to 44 kPa.min.L(-1) after intraperitoneal injection of 1mg.kg(-1) of LPS. The increments of PVF and PVP of PVL and IPO rats were significantly less than the sham-operated rats(P【0.01), There was no significant difference between the amounts of PVR decreased in the two groups of PHT model rats and sham-operated rats(P】0.05) after intraperitoneal injection 1mg.kg(-1) of LPS. CONCLUSION: Endotoxin could prompt portal hypertension of the normal and noncirrhotic portal hypertensive rats by increasing portal blood flow mainly.展开更多
Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE...Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study. All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge. We recorded incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding complications, and medication side effects. Results Seventy-eight consecutive patients were eligible and enrolled in this study. The mean hospital stat was 8.5±4.5 days. No symptomatic DVT, PE, or major bleeding events were observed. One patient developed wound ecchymosis, another developed wound bleeding, four had mild hepatic aminotransferase level elevation, and one developed a suspicious allergic reaction. Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression surgery.展开更多
Although most cases of acute nonvariceal gastrointestinal hemorrhage either spontaneously resolve or respond to medical management or endoscopic treatment,there are still a significant number of patients who require e...Although most cases of acute nonvariceal gastrointestinal hemorrhage either spontaneously resolve or respond to medical management or endoscopic treatment,there are still a significant number of patients who require emergency angiography and transcatheter treatment.Evaluation with noninvasive imaging such as nuclear scintigraphy or computed tomography may localize the bleeding source and/or confirm active hemorrhage prior to angiography.Any angiographic evaluation should begin with selective catheterization of the artery supplying the most likely site of bleeding,as determined by the available clinical,endoscopic and imaging data.If a hemorrhage source is identified,superselective catheterization followed by transcatheter microcoil embolization is usually the most effective means of successfully controlling hemorrhage while minimizing potential complications.This is now wellrecognized as a viable and safe alternative to emergency surgery.In selected situations transcatheter intra-arterial infusion of vasopressin may also be useful in controlling acute gastrointestinal bleeding.One must be aware of the various side effects and potential complications associated with this treatment,however,and recognize the high re-bleeding rate.In this article we review the current role of angiography,transcatheter arterial embolization and infusion therapy in the evaluation and management of nonvariceal gastrointestinal hemorrhage.展开更多
Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats we...Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)展开更多
AIM:To evaluate the effect of pantoprazole with a somatostatin adjunct in patients with acute non-variceal upper gastrointestinal bleeding(NVUGIB).METHODS:We performed a retrospective analysis of a prospective databas...AIM:To evaluate the effect of pantoprazole with a somatostatin adjunct in patients with acute non-variceal upper gastrointestinal bleeding(NVUGIB).METHODS:We performed a retrospective analysis of a prospective database in a tertiary care university hospital.From October 2006 to October 2008,we enrolled 101 patients with NVUGIB that had a high-risk stigma on endoscopy.Within 24 h of hospital admission,all patients underwent endoscopic therapy.After successful endoscopic hemostasis,all patients received an 80-mg bolus of pantoprazole followed by continuous intravenous infusion(8 mg/h for 72 h).The somatostatin adjunct group(n=49)also received a 250-μg bolus of somatostatin,followed by continuous infusion (250μg/h for 72 h).Early rebleeding rates,disappearance of endoscopic stigma and risk factors associated with early rebleeding were examined.RESULTS:Early rebleeding rates were not significantly different between treatment groups(12.2%vs 14.3%,P=0.766).Disappearance of endoscopic stigma on the second endoscopy was not significantly different between treatment groups(94.2%vs 95.9%,P=0.696).Multivariate analysis showed that the complete Rockall score was a significant risk factor for early rebleeding(P =0.044,OR:9.080,95%CI:1.062-77.595).CONCLUSION:The adjunctive use of somatostatin was not superior to pantoprazole monotherapy after successful endoscopic hemostasis in patients with NVUGIB.展开更多
Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CAB...Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62-0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47-0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54-1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P 〉 0.05 for all). The pre- sented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.展开更多
Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular di...Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.展开更多
Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interfe...Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interferon therapy. Chronic hepatitis C virus infection (genotype la) was diagnosed in a 33-year old asymptomatic man. His past medical history was unremarkable and previous routine ophthalmologic check-up was normal. Pegylated interferon alpha and ribavirin were started. Three weeks later he reported painless reduction of vision. Ophthalmologic examination showed extensive intraretinal hemorrhages and cottonwool spots, associated with inferior branch retinal vein thrombosis. Antiviral therapy was immediately discontinued, but one year later he persists with severely decreased visual acuity. This case illustrates the possibility of unpredictable and severe complications during pegylated interferon therapy.展开更多
In bilateral pbeochromocytoma, localization of the dominant adrenal is challenging but highly important since the removal of dominant side can markedly improve cardiovascular outcomes. To demonstrate the usefulness of...In bilateral pbeochromocytoma, localization of the dominant adrenal is challenging but highly important since the removal of dominant side can markedly improve cardiovascular outcomes. To demonstrate the usefulness of glucagon-stimulated BAVS (bilateral adrenal venous sampling) in determining the dominant adrenal to be removed, the authors reviewed records of patients who underwent BAVS with glucagon stimulation from 1997-2010. Nineteen out of 44 patients were diagnosed with bilateral pheochromocytoma. Mean age at diagnosis was 33 ± 14 years. Duration of hypertension was 5 ± 6 years with highest systolic BP (blood pressure) of 186 ±30 mmHg and diastolic BP of 113 ±18 mmHg. Headache (68%) is the most common symptom followed by paroxysmal hypertension (58%). Majority were taking 〉 3 anti-hypertensive drugs. On glucagon-stimulated BAVS, 63% had right adrenal dominance. Three patients, who were hypertensive for 1, 6 and 12 years, underwent removal of the dominant adrenal. On follow-up (mean period = 36 months), there was marked improvement in BP control [pre-op vs. post-op: (systolic) 160-240 mmHg vs. 120-150 mmHg; (diastolic) 90-110 mmHg vs. 70-90 mmHg] and reduction in number of anti-hypertensive medications (from 3-5 to 2 classes of drugs). BAVS with glucagon stimulation is a valuable tool in the identification of the dominant adrenal to be removed in patients with bilateral pheochromocytoma to alleviate chronic hypertension.展开更多
An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we...An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein(BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe儃/儃 mice infused with angiotensin II(AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species(ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2(MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor(AT1R) and inhibiting mitogen-activated protein kinases(MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention.展开更多
Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a re...Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican(a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.展开更多
OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat mo...OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin(STZ)(30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test(OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu(EX-B 3) group, EA Zusanli(ST 36)group, glimepiride group, and EA non-acupoint group(n = 12). EA(2 Hz continuous wave, 2 m A,20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, thestudy observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon-like peptide 1 receptor(GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4(GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R.RESULTS: EA Weiwanxiashu(EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices.CONCLUSION: EA Weiwanxiashu(EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu(EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.展开更多
Objective:Small intestinal bacterial overgrowth(SIBO)has been associated with several diseases.The association between SIBO and deep vein thrombosis(DVT)has not been investigated.This study was aimed to investigate th...Objective:Small intestinal bacterial overgrowth(SIBO)has been associated with several diseases.The association between SIBO and deep vein thrombosis(DVT)has not been investigated.This study was aimed to investigate the frequency and risk factors for the development of DVT in patients tested for SIBO.Methods:All 321 eligible patients were included from the Cleveland Clinic Gastrointestinal Motility Lab databank from January 2008 to January 2014.Patients who were evaluated with glucose hydrogen/methane breath test as well as Doppler ultrasonography for suspected DVT were included.Patients with catheter-related DVT were excluded.The primary outcomes were the frequency and risk factors(including SIBO)for DVT in this patient population.Results:Of the 321-case cohort,144 patients(44.9%)tested positive for SIBO,and 53(16.5%)had ultrasonographic findings of DVT.SIBO evaluation before the evaluation of DVT occurred in 201 patients(median time from the breath test to ultrasonography:27 months;interquartile range[IQR]:11.0–45.0 months),and SIBO evaluation after evaluation for DVT occurred in 120 patients(median time from ultrasonography to the breath test:30 months;IQR:11.8–54.3 months).In the univariate analysis,DVT was associated with family history of thromboembolic events(35.8%vs 16.0%,P=0.001),chronic kidney diseases(CKD;26.4%vs 13.4%,P=0.019)and the presence of SIBO(69.8%vs 39.9%,P50.001).In themultivariate analysis,family history of thromboembolic events(odds ratio[OR]:3.39;95%confidence interval[CI]:1.67–6.87;P50.001),CKD(OR:2.23;95%CI:1.04–4.74;P=0.037),and the presence of SIBO(OR:3.27;95% CI:1.70–6.32;P50.001)remained independently associated with DVT.Conclusion:SIBO was found to be associated with DVT.The nature of this association warrants further investigation.展开更多
基金National "Ninth five-year" Key Technology R&D Programme of China (Grant No.99-929-01-31)
文摘To investigate the effects of icariin (ICA) on angiotensin Ⅱ(Ang Ⅱ)-induced injury in human umbilical vein endothelial cells line (ECV-304). The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability (MTT method), Lactate dehydrogenase (LDH) release and Nitric oxide (NO) production in the medium, the capacity of scavenging superoxide anion radicals (O2^-) and hydroxyl radicals (.OH) were measured. The activities of superoxide dismutase (SOD), total nitric oxide synthase (T-NOS), inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals ( O2^- ) and hydroxyl radicals(.OH), and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells (ECV-304) from Ang II-induced injury.
文摘Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.
文摘Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.
文摘AIM: To study the effects of endotoxin on portal hemodynamic of normal and noncirrhotic portal hypertensive rats. METHODS: Normal rats were intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of lipopolysaccharide(LPS) respectively, portal vein ligation(PVL) and intrahepatic portal occlusion (IPO) rats as well as sham-operated rats were treated with an intraperitoneal injection of 1.0mg.kg(-1) of LPS, the portal vein pressure(PVP), portal venous flow(PVF), inferior vena cava pressure(IVCP) and portal vein resistance(PVR) were detected 4 hours after injection. RESULTS: PVF of the 5 groups of rats accepting intraperitoneal injection of LPS were increased from 14.0 to 18.0, 22.2, 26.2, 34.8, 39.6, 38.8 mL.min(-1) 4 hours after injection of LPS(P【0.01). PVP of the 4 groups of rats accepting more than 0.1mg/kg.b.w of LPS was increased from 1.04 to 1.25, 1.50, 1.80, 1.95, 2.05 kPa(P【0.01). The increments of PVF and PVP were in a dose-dependent manner of LPS. PVR of the 5 groups of rats was decreased from 51 to 42,44,48,45,44,47 kPa.min.L(-1) (P【0.05) and no dose-dependent manner was observed. PVF of PVL, IPO and sham-operated rats increased from 22.6 to 32.8, 22.0 to 28.0, 14.0 to 34.8 mL.min(-1) (P【0.01), and PVP increased from 1.86 to 2.24, 1.74 to 1.95, 1.04 to 1.80 kPa(P【0.01), PVR decreased from 71 to 61, 67 to 61, 52 to 44 kPa.min.L(-1) after intraperitoneal injection of 1mg.kg(-1) of LPS. The increments of PVF and PVP of PVL and IPO rats were significantly less than the sham-operated rats(P【0.01), There was no significant difference between the amounts of PVR decreased in the two groups of PHT model rats and sham-operated rats(P】0.05) after intraperitoneal injection 1mg.kg(-1) of LPS. CONCLUSION: Endotoxin could prompt portal hypertension of the normal and noncirrhotic portal hypertensive rats by increasing portal blood flow mainly.
文摘Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study. All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge. We recorded incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding complications, and medication side effects. Results Seventy-eight consecutive patients were eligible and enrolled in this study. The mean hospital stat was 8.5±4.5 days. No symptomatic DVT, PE, or major bleeding events were observed. One patient developed wound ecchymosis, another developed wound bleeding, four had mild hepatic aminotransferase level elevation, and one developed a suspicious allergic reaction. Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression surgery.
文摘Although most cases of acute nonvariceal gastrointestinal hemorrhage either spontaneously resolve or respond to medical management or endoscopic treatment,there are still a significant number of patients who require emergency angiography and transcatheter treatment.Evaluation with noninvasive imaging such as nuclear scintigraphy or computed tomography may localize the bleeding source and/or confirm active hemorrhage prior to angiography.Any angiographic evaluation should begin with selective catheterization of the artery supplying the most likely site of bleeding,as determined by the available clinical,endoscopic and imaging data.If a hemorrhage source is identified,superselective catheterization followed by transcatheter microcoil embolization is usually the most effective means of successfully controlling hemorrhage while minimizing potential complications.This is now wellrecognized as a viable and safe alternative to emergency surgery.In selected situations transcatheter intra-arterial infusion of vasopressin may also be useful in controlling acute gastrointestinal bleeding.One must be aware of the various side effects and potential complications associated with this treatment,however,and recognize the high re-bleeding rate.In this article we review the current role of angiography,transcatheter arterial embolization and infusion therapy in the evaluation and management of nonvariceal gastrointestinal hemorrhage.
文摘Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)
基金Supported by A grant of the Korea Healthcare technology R&D Project,Ministry for Health,Welfare&Family Affairs,Republic of Korea NO.A091047 Medical Research Institute Grant (2009-1),Pusan National University
文摘AIM:To evaluate the effect of pantoprazole with a somatostatin adjunct in patients with acute non-variceal upper gastrointestinal bleeding(NVUGIB).METHODS:We performed a retrospective analysis of a prospective database in a tertiary care university hospital.From October 2006 to October 2008,we enrolled 101 patients with NVUGIB that had a high-risk stigma on endoscopy.Within 24 h of hospital admission,all patients underwent endoscopic therapy.After successful endoscopic hemostasis,all patients received an 80-mg bolus of pantoprazole followed by continuous intravenous infusion(8 mg/h for 72 h).The somatostatin adjunct group(n=49)also received a 250-μg bolus of somatostatin,followed by continuous infusion (250μg/h for 72 h).Early rebleeding rates,disappearance of endoscopic stigma and risk factors associated with early rebleeding were examined.RESULTS:Early rebleeding rates were not significantly different between treatment groups(12.2%vs 14.3%,P=0.766).Disappearance of endoscopic stigma on the second endoscopy was not significantly different between treatment groups(94.2%vs 95.9%,P=0.696).Multivariate analysis showed that the complete Rockall score was a significant risk factor for early rebleeding(P =0.044,OR:9.080,95%CI:1.062-77.595).CONCLUSION:The adjunctive use of somatostatin was not superior to pantoprazole monotherapy after successful endoscopic hemostasis in patients with NVUGIB.
文摘Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62-0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47-0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54-1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P 〉 0.05 for all). The pre- sented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.
基金This work was supported by National Natural Science Foundation of China (NSFC) (No. 81400265 and No. 81270274), and Peking University People's Hospital Research and Development funds (RDB2014-16).
文摘Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.
文摘Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interferon therapy. Chronic hepatitis C virus infection (genotype la) was diagnosed in a 33-year old asymptomatic man. His past medical history was unremarkable and previous routine ophthalmologic check-up was normal. Pegylated interferon alpha and ribavirin were started. Three weeks later he reported painless reduction of vision. Ophthalmologic examination showed extensive intraretinal hemorrhages and cottonwool spots, associated with inferior branch retinal vein thrombosis. Antiviral therapy was immediately discontinued, but one year later he persists with severely decreased visual acuity. This case illustrates the possibility of unpredictable and severe complications during pegylated interferon therapy.
文摘In bilateral pbeochromocytoma, localization of the dominant adrenal is challenging but highly important since the removal of dominant side can markedly improve cardiovascular outcomes. To demonstrate the usefulness of glucagon-stimulated BAVS (bilateral adrenal venous sampling) in determining the dominant adrenal to be removed, the authors reviewed records of patients who underwent BAVS with glucagon stimulation from 1997-2010. Nineteen out of 44 patients were diagnosed with bilateral pheochromocytoma. Mean age at diagnosis was 33 ± 14 years. Duration of hypertension was 5 ± 6 years with highest systolic BP (blood pressure) of 186 ±30 mmHg and diastolic BP of 113 ±18 mmHg. Headache (68%) is the most common symptom followed by paroxysmal hypertension (58%). Majority were taking 〉 3 anti-hypertensive drugs. On glucagon-stimulated BAVS, 63% had right adrenal dominance. Three patients, who were hypertensive for 1, 6 and 12 years, underwent removal of the dominant adrenal. On follow-up (mean period = 36 months), there was marked improvement in BP control [pre-op vs. post-op: (systolic) 160-240 mmHg vs. 120-150 mmHg; (diastolic) 90-110 mmHg vs. 70-90 mmHg] and reduction in number of anti-hypertensive medications (from 3-5 to 2 classes of drugs). BAVS with glucagon stimulation is a valuable tool in the identification of the dominant adrenal to be removed in patients with bilateral pheochromocytoma to alleviate chronic hypertension.
基金supported by the National Natural Science Foundation of China(31571193,81422002,91339201)
文摘An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein(BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe儃/儃 mice infused with angiotensin II(AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species(ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2(MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor(AT1R) and inhibiting mitogen-activated protein kinases(MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention.
基金supported by the National Natural Science Foundation of China(81170287)
文摘Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican(a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.
基金Supported by Ministry of Education of the People's Republic of China:a Mechanism Study of Electro-Acupuncture EX-B3's Effect on Pancreas PDX-1 of Goto-Kakizaki Rats(No.313010)
文摘OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin(STZ)(30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test(OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu(EX-B 3) group, EA Zusanli(ST 36)group, glimepiride group, and EA non-acupoint group(n = 12). EA(2 Hz continuous wave, 2 m A,20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, thestudy observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon-like peptide 1 receptor(GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4(GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R.RESULTS: EA Weiwanxiashu(EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices.CONCLUSION: EA Weiwanxiashu(EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu(EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.
文摘Objective:Small intestinal bacterial overgrowth(SIBO)has been associated with several diseases.The association between SIBO and deep vein thrombosis(DVT)has not been investigated.This study was aimed to investigate the frequency and risk factors for the development of DVT in patients tested for SIBO.Methods:All 321 eligible patients were included from the Cleveland Clinic Gastrointestinal Motility Lab databank from January 2008 to January 2014.Patients who were evaluated with glucose hydrogen/methane breath test as well as Doppler ultrasonography for suspected DVT were included.Patients with catheter-related DVT were excluded.The primary outcomes were the frequency and risk factors(including SIBO)for DVT in this patient population.Results:Of the 321-case cohort,144 patients(44.9%)tested positive for SIBO,and 53(16.5%)had ultrasonographic findings of DVT.SIBO evaluation before the evaluation of DVT occurred in 201 patients(median time from the breath test to ultrasonography:27 months;interquartile range[IQR]:11.0–45.0 months),and SIBO evaluation after evaluation for DVT occurred in 120 patients(median time from ultrasonography to the breath test:30 months;IQR:11.8–54.3 months).In the univariate analysis,DVT was associated with family history of thromboembolic events(35.8%vs 16.0%,P=0.001),chronic kidney diseases(CKD;26.4%vs 13.4%,P=0.019)and the presence of SIBO(69.8%vs 39.9%,P50.001).In themultivariate analysis,family history of thromboembolic events(odds ratio[OR]:3.39;95%confidence interval[CI]:1.67–6.87;P50.001),CKD(OR:2.23;95%CI:1.04–4.74;P=0.037),and the presence of SIBO(OR:3.27;95% CI:1.70–6.32;P50.001)remained independently associated with DVT.Conclusion:SIBO was found to be associated with DVT.The nature of this association warrants further investigation.