The analysis of lipids and glycosaminoglycans of low-density lipoprotein-glycosaminoglycans complexes isolated from normal, fatty streaks and fibrous plaques of human aortic intima

The low-density lipoproteins (LDL)-glycosaminoglycans (GAG) complexes were isolated from fibrous plaques, fatty streaks and normal of human aortic intima and analysed for lipids and GAGs. The LDL-GAG complexes formed a precipitation line against antihuman apoprotein B, which is a major component of plasma LDL, and the lipids constituents of LDL-GAG complexes resembled those of plasma LDL. It might be suggested from these findings that the lipoproteins (LP) bound to GAG in arterial tissue was originated from plasma LDL penetrated into arterial tissue from circulating system. From the analysis of GAGs in LDL-GAG complexes by two-dimensional electrophoresis, the % composition of GAG in fibrous plaques showed higher in chondroitin-4-sulfate (CS-4-S) plus chondroitin-6-sulfate (CS-6-S) and marked lower in dermatan sulfate (DS) when compared with those of fatty streaks. There are no differences in the % composition of hyaluronic acid (HA) in normal and atherosclerotic lesions. It would be suggested from these observations that the formation of saline extractable LDL-GAG complexes would be the early events in aortic intima when plasma LDL penetrated from circulation system and that not only DS and/or heparan sulfate (HS) but also CS-4-S and/or CS-6-S have an important role on the progression of atherosclerosis.     

糖尿病患者Apo－Al、Apo－B测定及其临床意义

本文对６０例糖尿病患者及６２例正常人的血清载脂蛋白（Ａｐｏ）－Ａｌ，Ａｐｏ－Ｂ高密度脂蛋白（ＨＤＬ）和低密度脂蛋白（ＬＤＬ）水平进行了测定，结果显示：（１）糖尿病患者Ａｐｏ－Ａｌ水平和Ａｐｏ－Ｂ水平均明显高于正常人（Ｐ＜０．０１）。（２）住院治疗前，糖尿病患者血清ＨＤＬ水平明显低于正常人（Ｐ＜０．０１）。（３）住院治疗期间糖尿病患者血清ＨＤＬ水平显著增高（Ｐ＜０．０１），而ＬＤＬ水平无明显改变（Ｐ＞０．０５）。     

糖尿病患者Apo－Al、Apo－B测定及其临床意义

本文对６０例糖尿病患者及６２例正常人的血清载脂蛋白（Ａｐｏ）－Ａｌ，Ａｐｏ－Ｂ高密度脂蛋白（ＨＤＬ）和低密度脂蛋白（ＬＤＬ）水平进行了测定，结果显示：（１）糖尿病患者Ａｐｏ－Ａｌ水平和Ａｐｏ－Ｂ水平均明显高于正常人（Ｐ＜０．０１）。（２）住院治疗前，糖尿病患者血清ＨＤＬ水平明显低于正常人（Ｐ＜０．０１）。（３）住院治疗期间糖尿病患者血清ＨＤＬ水平显著增高（Ｐ＜０．０１），而ＬＤＬ水平无明显改变（Ｐ＞０．０５）。     

Electronegative low density lipoprotein subform (LDL–) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation

There is increasing evidence that diabetes mellitus is characterized by an enhanced lipoprotein oxidation. We have therefore investigated whether a relationship exists between LDL oxidation and microalbuminuria, which is considered an early marker of vascular involvement in type 2 diabetic patients. We selected 12 microalbuminuric and 12 normoalbuminuric type 2 diabetic patients, and 12 control subjects comparable for age, sex and blood pressure values. Oxidatively modified plasma LDL, referred as LDL^–, were measured by ion-exchange HPLC. In vitro susceptibility to oxidation of LDL was evaluated by following the kinetics of conjugated diene formation in the presence of Cu⁺⁺ ions (lag-phase time). Microalbuminuric diabetic patients had a less satisfactory metabolic control and showed a higher plasma triglyceride concentration than both normoalbuminuric diabetic patients (2.21±1.01 vs 1.15±0.39 mmol/l, P<0.01) and controls (1.18±0.61 mmol/l, P<0.01). The percentage of LDL^– in plasma was significantly increased in microalbuminuric diabetic patients in comparison with both normoalbuminuric diabetic patients (5.24±1.67 vs 3.13±1.22%, P<0.01) and controls (2.34±1.03%, P<0.001). LDL isolated from microalbuminuric diabetic patients had a significantly shorter lag-phase time in comparison with normoalbuminuric diabetic patients (79±11 vs 97±10 min, P<0.05) and controls (120±24 min, P<0.001). In diabetic patients a significant linear correlation was observed between the percentage of LDL^– and amount of fructosamine (r=0.45, P<0.05), HbA_1c (r=0.41, P<0.05), and triglycerides (r=0.65, P<0.001). An inverse correlation was found between lag-phase time and fructosamine (r=–0.5, P<0.01) and triglycerides (r=–0.59, P<0.001). This study shows that microalbuminuric type 2 diabetic patients had evidence of increased LDL oxidation, which seems to be mainly due to a poor metabolic control and a more atherogenic lipid profile. Received: 9 March 1998 / Accepted in revised form: 24 June 1998     

The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia

Summary Using I¹³¹ VLDL selectively labelled in the B-apoprotein and I¹²⁵ LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72–83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21–28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.     

Rationale and design of the ETN-STEP (Early administration of Tirofiban in mid to high risk patients with non-ST elevation acute coronary syndrome referred for percutaneous coronary intervention) project: A multi-center, randomized, controlled clinic trial in Chinese patients

As a member of Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, Tirofiban had been shown to improve myocardial reperfusion and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), but the optimal timing of administration of Tirofiban remains unclear. In order to compare the effects of upstream versus downstream administration of Tirofiban in Chinese patients with mid to high risk, non-ST elevation acute coronary syndrome (ACS) referred for PCI, a multicenter, randomized, controlled, prospective study will be conducted. A total of 500 mid to high risk, non-ST-segment elevation myocardial infarction (NSTEMI) ACS patients will be recruited for this study. Patients will be randomized to Tirofiban upstream administration group (initiated 12 h before PCI) and Tirofiban downstream administration group (initiated at cath-lab after angiography). Thrombolysis in myocardial infarction (TIMI) flow grades, TIMI myocardial perfusion grades (TMPG), and Corrected TIMI frame counting (CTFC) before and after PCI, as well as clinical outcomes during the hospital stay, and within 30 days after PCI will be compared between the two groups. This study will provide evidence on the optimal timing for initiating administration of Tirofiban in mid to high NSTEMI ACS subjects undergoing PCI.     

High‐Efficiency DALI Apheresis Using 1,250 ml Adsorbers in a Hypercholesterolemic Obese Patient: A Case Report

Abstract: Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins from whole blood and is therefore an easy and rapid procedure. The majority of patients reaches >60% acute low‐density lipoprotein cholesterol (LDL‐C) reduction using either the DALI 750 or 1000 configuration. However, in patients with extremely high LDL‐C levels or very large blood volumes, these configurations may lead to suboptimal results. The current study was performed to test the safety and efficacy of DALI 1250. In a severely obese patient (185 cm, 133 kg, blood volume 7.2 L, LDL‐C 239 mg/dl), 11 L of blood (1.53‐fold patient blood volume) was processed at a flow rate of 80 ml/min in 2.5 h; a combined heparin‐plus‐citrate anticoagulation regimen was used. Commercially available DALI 1250 and DALI hardware and disposables were manufactured by Fresenius HemoCare Adsorber Technology, St. Wendel, Germany. Twenty weekly sessions were performed. Clinically and technically, the apheresis sessions were completely uneventful. As compared to DALI 1000 (n = 4 sessions), the reduction rates by DALI 1250 (n = 20) improved for LDL‐C (from 52% to 66%), lipoprotein (a) (Lp[a]) (53% vs. 66%), and fibrinogen (11% vs. 16%). There was a slight increase in high‐density lipoprotein cholesterol (HDL‐C) loss (20% vs. 24%). Moreover, the absolute amount of LDL‐C removed per session increased from 5.06 g to 5.94 g. Laboratory safety parameters remained within the normal range, the anticoagulation was well controlled, and the pressure gradients over the adsorber remained constant. In this case report, DALI 1250 was perfectly safe and significantly increased the efficacy of LDL‐C and Lp(a) elimination compared to standard DALI. Thus, this high‐efficiency version of DALI may be used in patients with extremely high LDL‐C levels and/or large blood volumes.     

Pharmacological Effects of Xanthones as Cardiovascular Protective Agents

Many epidemiological studies indicate that consumption of dietary polyphenolic compounds is beneficial in the prevention of cardiovascular diseases. Xanthones are a class of polyphenolic compounds that commonly occur in plants and have been shown to have extensive biological and pharmacological activities. Recently, the pharmacological properties of xanthones in the cardiovascular system have attracted great interest. Xanthones and xanthone derivatives have been shown to have beneficial effects on some cardiovascular diseases, including ischemic heart disease, atherosclerosis, hypertension and thrombosis. The protective effects of xanthones in the cardiovascular system may be due to their antioxidant, antiinflammatory, platelet aggregation inhibitory, antithrombotic and/or vasorelaxant activities. In particular, the antagonism of endogenous nitric oxide synthase inhibitors by xanthones may represent the basis for improved endothelial function and for reduction of events associated with atherosclerosis.     

CER-001, a HDL-mimetic,stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice

Objective

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr^−/− mice after short-term multiple-dose infusions.

Approach and results

CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10 mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively.

Conclusion

These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr^−/− mice upon a short-term multiple dose treatment.     

Increased proportion of proapoliporotein A-I in HDL from patients with liver cirrhosis and hepatitis

We examined the isoform pattern of apolipoprotein A-I (apo A-I) in high density lipoprotein from patients with liver disease. An increase in the proportion of proapo A-I was evident in patients with decompensated liver cirrhosis, acute hepatitis and hepatocellular carcinoma. The rate of conversion from proapo A-I to apo A-I was low in sera from those with liver disease, compared to normal controls. The proportion of proapo A-I showed a tendency toward increase with advance in liver damage. These results suggest that the liver is participating in the reaction converting proapo A-I to the mature apo A-I.     

核苷(酸)类似物抗病毒治疗对慢性乙肝患者血脂异常的潜在影响及其临床意义

慢性乙型肝炎病毒感染及相关肝病仍是我国重要的公共卫生问题.目前,核苷(酸)类似物是抗病毒治疗的一线用药,但其长期服用的安全性问题也引起了临床医师的广泛关注.近期亚太肝病学会(APASL)会议报道长期富马酸丙酚替诺福韦治疗中伴发的低密度脂蛋白胆固醇水平升高,谨慎评价这种抗病毒治疗过程中的血脂异常,探讨其对终末期肝病发生风...     

Hypertriglyceridaemia and its influence on low density lipoprotein regulation of cellular cholesterol synthesis: a comparison between hypertriglyceridaemic diabetic and non-diabetic patients.

The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non-insulin-dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol less than 6.5 mmol l-1) and hypercholesterolaemic (serum cholesterol greater than 6.5 mmol l-1) with and without hypertriglyceridaemia (serum triglyceride greater than or less than 3.5 mmol l-1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]-acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 +/- 0.04 vs 0.76 +/- 0.04 g g-1; p less than 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non-diabetic or diabetic patients compared with LDL from the normocholesterolaemic non-diabetic control subjects (47.4 +/- 3.9%, 39.1 +/- 5.1% and 35.2 +/- 4.1% vs 59.5 +/- 1.2%, p less than 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.     

Cholesterol synthesis in isolated rat hepatocytes: effect of homologous and heterologous serum lipoproteins.

The present study investigated the effect of serum lipoproteins on sterol synthesis by isolated rat hepatocytes. These cells were maintained in culture medium for 24 hr and incubated for the same period of time with increasing concentrations of serum lipoproteins (5-150 microgram of lipoprotein-protein per ml) isolated from different animal species. The viability of the cells was ascertained by their ability to synthesize cholesterol and protein and to secrete serum proteins into the medium. Rat VLDL and LDL did not alter sterol synthesis, which was stimulated instead by HDL. Rat serum chylomicrons were also ineffective. Human LDL significantly reduced the synthesis of sterols from both acetate and tritiated water; this effect was also induced by human VLDL to a reduced extent. VLDL isolated from hypercholesterolemic rabbit (VLDLC) strongly inhibited sterol synthesis from acetate but not from mevalonate. Cholesteryl-ester-rich VLDL isolated from a patient with type III hyperlipidemia (type III VLDL) were more effective than normal VLDL in suppressing sterol synthesis from acetate. The implications of these findings are discussed with regard to the possible role of cholesteryl-ester-rich lipoproteins on the in vivo regulation of sterol synthesis in the liver.     

高血压病患者颈动脉粥样硬化程度与血清脂蛋白(a)和胆红素水平的关系

目的探讨血清脂蛋白(a)和胆红素水平变化与颈动脉粥样硬化程度的关系。方法选择高血压病患者124例,进行颈动脉超声检查,根据颈动脉粥样硬化程度(狭窄)程度分为内膜增厚组、内膜斑块形成组、管腔轻度狭窄组、管腔中度狭窄组和管腔重度狭窄组5组,同时检测血清脂蛋白(a)和胆红素水平,并进行统计学分析。结果颈动脉粥样硬化程度加重时,在5组血清脂蛋白(a)分别为156.7±89.2mg/L,237.0±170.3mg/L,324.0±126.0mg/L,331.9±197.5mg/L和346.2±124.0mg/L,前3组间差异有显著性(P<0.05),血清总胆红素分别为12.4±2.6μmol/L,10.7±1.4μmol/L,9.1±1.0μmol/L,8.1±0.9μmol/L和7.1±0.8μmol/L,间接胆红素分别为9.1±2.4μmol/L,7.4±1.5μmol/L,5.9±1.2μmol/L,4.9±0.8μmol/L和3.9±0.8μmol/L,5组间差异有显著性(P<0.01),而直接胆红素差异无显著性(P>0.05)。脂蛋白(a)与总胆红素、间接胆红素水平显著负相关(r=-0.332和-0.331,P均<0.01)。结论高血压病患者的血清脂蛋白(a)和胆红素水平变化与动脉粥样硬化关系密切。     

Effect of Nicotinic acid/Laropiprant in the lipoprotein(a) concentration with regard to baseline lipoprotein(a) concentration and LPA genotype

Background

Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100 is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a) concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on Lp(a) has been previously reported.

Objective

To evaluate the Lp(a) lowering effect of 1 g/20 mg and 2 g/40 mg day of Nicotinic acid/Laropiprant in subjects with different baseline Lp(a) concentrations and depending on the LPA genotype.

Methods

In an open-label, 10-week study, 1 g/20 mg day of NA/Laropiprant for 4 weeks followed by 6 weeks of 2 g/40 mg day conducted at 3 centers in Spain, 82 subjects were enrolled. Patients were studied at baseline and at the end of both treatment periods and were enrolled in three groups: normal Lp(a) (< 50 mg/dL), high Lp(a) (50–120 mg/dL) and very high Lp(a) (> 120 mg/dL). The LPA genetic polymorphism was analyzed by a real-time PCR.

Results

There was a significant difference in LPA genotypes among Lp(a) concentration groups and an inverse and significant correlation between baseline Lp(a) concentration and LPA genotype was found (R = − 0.372, p < 0.001). There were a significant decrease in total cholesterol, triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However, there were no statistical differences in percentage variation of analyzed variables depending on LPA genotype.

Conclusion

LPA genotype is a major determinant of Lp(a) baseline concentration. However, the lipid lowering effect of NA is not related to LPA genotype.     

同型半胱氨酸 血尿酸水平与腔隙性脑梗死患者动脉粥样硬化的相关性研究

目的探讨血清同型半胱氨酸(Hcy)、血尿酸(SUA)水平与腔隙性脑梗死患者动脉粥样硬化的相关性。方法选取2012-11~2015-10该院住院的腔隙性脑梗死患者93例作为脑梗死组,根据超声检查结果分为动脉内膜中层厚度(IMT)正常组26例,IMT增厚组22例,斑块组45例三个亚组,另选择同期90名健康体检者作为正常对照组,比较各组间Hcy、SUA水平及IMT值,并分析指标间相关性。结果脑梗死组血清Hcy、SUA水平均明显高于正常对照组(P0.01)。脑梗死组内各亚组之间血清Hcy、SUA水平及IMT值比较差异均有统计学意义(P0.05),其中IMT增厚组和斑块组各指标均明显高于IMT正常组(P0.05),而斑块组各指标则均明显高于IMT增厚组(P0.05)。经Pearson相关性分析显示腔隙性脑梗死患者IMT值与血清Hcy、SUA水平之间均呈正相关(P0.05)。结论腔隙性脑梗死患者血清Hcy、SUA水平明显增高,且血清Hcy、SUA水平升高与颈动脉粥样硬化的发生密切相关。     

miRNA-21/101/125a/195/200b在肝硬化、肝癌中的表达变化

目的观察microRNA(miRNA)-21/101/125a/195/200b在肝硬化、肝癌中的表达变化。方法收集患者肝组织样本,其中血管瘤6份、肝硬化10份,肝癌及癌旁组织14对;除血管瘤外,其余样本均HBsAg阳性。PCR检测各组miR-21、miR-101、miR-125a、miR-195、miR-200b的表达。采用Pearson相关性分析探索miR-101的表达与临床相应指标之间的相关性。结果与对照组相比,肝硬化组血小板(PLT)明显降低,凝血酶原时间(PT)延长、国际标准化比值(INR)升高,天门冬氨酸氨基转移酶(AST)和总胆红素(TBil)升高;HE染色、Masson染色及网状纤维染色显示符合肝硬化诊断。与肝硬化组相比,肝癌组白细胞(WBC)、PLT均有所升高,PT、INR降低,AST、TBil表达下降;与对照组、肝硬化组相比,肝癌组甲胎蛋白(AFP)表达显著升高,免疫组化染色符合肝癌诊断。PCR检测miRNA的表达,与对照组相比,miR-101、miR-195在肝硬化组中的表达下降;与癌旁组织相比,miR-21在肝癌中的表达升高,miR-101、miR-195的表达则显著降低。miR-125a、miR-200b的表达在各组间无明显变化。Pearson相关性分析发现miR-101与PLT表达水平呈正相关,相关系数为0.375。结论 miR-101在肝硬化、肝癌组织中表达降低,且与血小板水平呈正相关,提示miR-101是慢性肝病的负调控因子。     

Effect of fatty liver and fibrosis on hepatocellular carcinoma development in patients with chronic hepatitis B who received nucleic acid analog therapy

The number of patients with fatty liver has been increasing worldwide; however, the significance of fatty liver in patients with chronic hepatitis B who are receiving nucleic acid analog (NA) therapy remains unclear. Thus, we aimed to determine whether fatty liver affects the development of hepatocellular carcinoma (HCC) in patients receiving NA therapy. This study included 445 patients who received NA therapy, and the development of HCC was investigated. The primary outcome was the association between fatty liver and HCC development. During a mean follow-up period of 7.4 years, 46 patients (10.3%) developed HCC. No significant difference in the cumulative incidence of HCC was observed between patients with fatty liver and those without (p = 0.17). Multivariable analysis for age, gender, platelet count, alanine aminotransferase level at 1 year following NA therapy, and fatty liver revealed that the presence of fatty liver was not a significant factor for HCC development (hazard ratio [HR]: 0.96, 95% confidence interval [CI]: 0.5–1.9). In another multivariable analysis for advanced fibrosis, gender, and fatty liver, advanced fibrosis was found to be a significant factor for HCC development (HR: 9.50, 95% CI: 5.1–18) but not fatty liver (HR: 0.90, 95% CI: 0.5–1.7). In conclusion, in patients with chronic hepatitis B who received NA therapy, advanced fibrosis was found to be an important risk factor for HCC development but not fatty liver, suggesting the importance of providing treatment before the progression of liver fibrosis regardless of the presence of fatty liver.     

糖基化终产物对人脐静脉内皮细胞血管内皮生长因子mRNA及蛋白表达的影响

目的研究糖基化终产物（AGEs）对人脐静脉山皮细胞血管内皮生长凼子（VEGF）mRNA及蛋白表达的影响，探讨AGEs在糖尿病动脉粥样硬化中的作用。方法将人脐静脉内皮细胞株ECV304用BSA及小同浓度的AGEs孵育24h及400mg／L的AGEs孵育0、12、24及36h，采用原位杂交及Westem blot方法检测VEGFmRNA及蛋白的表达。结果人脐静脉内皮细胞在100、200及400mg／LAGEs孵育24h后，VEGFmRNA及蛋白表达均显著高于BSA对照组（P〈0．05），在用400mg／LAGEs分别孵育12．24及36h后，各组内皮细胞VEGF mRNA及蛋白表达量也明显高于0h对照组（P〈O．05）。结论AGEs可增加人脐静脉内皮细胞VEGF mRNA及蛋白的表达，且与浓度和时间呈正相关。     

Use of NT-proBNP in routine testing and comparison to BNP

OBJECTIVES: B-type natriuretic peptide (BNP) is a strong diagnostic predictor of left-ventricular (LV)-dysfunction. Recently, the aminoterminal portion of pro-BNP (NT-proBNP) has been introduced, which could be even more sensitive because of its longer half-life. The aim of this study was to evaluate the new marker NT-proBNP within a large, heterogeneous population of patients with suspected cardiovascular disease at risk of cardiovascular dysfunction and to compare it with the established diagnostic parameter BNP. SUBJECTS AND METHODS: NT-proBNP and BNP were measured in 339 hospitalised patients undergoing diagnostic angiography (median age 66 years, 244 male vs. 95 female). RESULTS: Median values of NT-proBNP increased with worsening LV-dysfunction and higher NYHA class. The area under the receiver operator characteristics curve (AUC) of NT-proBNP for detecting severe systolic dysfunction or for detecting any systolic LV-dysfunction was 0.83 and 0.77, respectively. The latter improved (AUC=0.81) when patients with clinically relevant heart disease like valvular dysfunction were included, independent of the haemodynamic values. Compared to BNP, NT-proBNP tended to be more accurate in identifying lesser degrees of LV-dysfunction. CONCLUSIONS: Even after optimisation of target criteria, there was still a substantial overlap of NT-proBNP values between patients with and without relevant heart disease. Therefore, NT-proBNP is not suitable as a screening test for LV-dysfunction in the community. Nevertheless, because of its good negative predictive value, NT-proBNP could be an easy and effective tool to rule out severe systolic LV-dysfunction in high risk patients. No clinically significant advantage of BNP testing could be found.