Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells

Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC₅₀ values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier.     

Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a University Rheumatology clinic. The controls came from the same reference area. Subjects. Altogether 17 consecutive post-menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF-α; interleukin 1β, IL-1β; and interleukin-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load. Results. Pre-heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r_s=?0.63, P<0.05) and C-reactive protein (CRP) (r_s=?0.54, P<0.05) and close to significant for haptoglobin (r_s=?0.48, P=0.087) and IL-6 (r_s=?0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.     

北京市城乡乳母的营养状况、乳成分和婴儿摄入母乳量及生长发育的关系——Ⅲ母乳的脂质分析

本文报导了1983～1984年北京市城区(宣武区),近郊区(西红门)和远郊区(大皮营)母乳脂质成分的测定结果,并结合乳母营养状况给予评价。 共测定了207例母乳比重,平均范围在1.018～1.023之间;测定了216例母乳的脂肪含量(g/100g乳),城区平均值为3.78,近郊区为3.31,远郊区为3.08,城区的显著较高;测定了194例母乳胆固醇含量,初乳的最高(23.4mg/100g乳),以后逐渐减低,到第三个月后达稳定水平(约10mg/100g乳),三个调查点的情况相同,测定了221例母乳的脂肪酸组成,其主要成分为油酸(29～37％),棕榈酸(17～25％)和亚油酸(12～25％),远郊区母乳中所含的必需脂肪酸显著较高。 统计分析证明三个地区的乳脂含量(％)与乳胆固醇含量(mg/100g乳)间有显著性相关(P<0.01);188例乳母的膳食脂肪摄入量(g/日或％kcal)与乳脂含量间也有显著性相关(P<0.05),此结果表明,北京城乡母乳的乳脂含量可能受膳食脂质与量的影响,其脂肪酸组成的特点是亚油酸含量高,反映了我国人民以素食为主的饮食习惯。乳中的必需脂肪酸供给量可满足婴儿所需,胆固醇供给量为70～85mg/d,可作为同龄婴儿自母乳摄入量的参考。     

抑郁症患者的血糖、血脂水平及其与症状关系的对照研究

目的了解抑郁症患者糖脂代谢的情况及其与精神症状的关系。方法以HAMD17和HAMA评定92例近期未服用精神药物的抑郁症患者的精神症状,了解他们简易体质参数、测定其空腹血糖和血脂,并与60例健康者组成的对照组进行比较。结果抑郁症组的甘油三酯(TG)、空腹血糖(FBS)值显著高于对照组(P＜0．001),而高密度脂蛋白胆固醇(LDL—ch)、载脂蛋白A1(ApoA1)值显著低于对照组(P＜0．01)；血浆总胆固醇(TC)、高密度脂蛋白胆固醇(HDL—ch)和载脂蛋白B(ApoB)两组之间无显著性差异(P＞0．05)；相关分析发现,抑郁症患者的HAMA总分、精神性焦虑因子分以及躯体性焦虑因子分与TG水平呈正相关(P＜0．01或P＜0．05)。结论抑郁症患者存在一定的糖脂代谢异常,临床医师应该对抑郁症患者的血糖、血脂进行监测,以便早期发现,早期治疗。     

Reduction of Mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by Combined Treatment with Clofibrate and Nicotinic Acid

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n=276) and a Treatment group (n=279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p<0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p<0.05). IHD mortality was reduced by 36% (p<0.01)in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level >1.5 mmol/l (n=216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride concentration by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p<0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13 %. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was reponsible for the beneficial effect of the treatment.     

冠心病病人氧化修饰低密度脂蛋白的测定及临床意义

目的 :探讨氧化修饰低密度脂蛋白 (Ox LDL)对冠心病 (CHD)形成和发展的影响。方法 :CHD组 6 0例 ,对照组 5 3例。用酶标多克隆抗体夹心的方法检测血清Ox LDL含量。结果 :CHD组血清Ox LDL含量为 ( 48.6± 32 .8) μg dl。对照组( 2 5 .9± 2 2 .5 ) μg dl,两组之间Ox LDL含量存在显著性差异 (P <0 .0 0 1)。 结论 :Ox LDL和CHD有密切的关系 ,故可作为CHD病人特异性的辅助诊断指标。     

Lens opacity in patients with hypercholesterolemia and ischaemic heart disease

Lens opacity studies were performed using an electronic Lens Opacity Meter (Interzeag Opacity Lensmeter 701) in a population (n = 321) with ischaemic heart disease. These patients are participating in a trial targetting at the reduction of mortality and incidence of myocardial infarction using a cholesterol-lowering drug, simvastatin. A separate study to evaluate the reliability of the method showed good reproducibility. Repeated measurements after a short time-interval (2–10 days) gave statistically lower opacity values either due to a change in lens transparency or perhaps a change in pigment and cell dispersion in the acqueous caused by repeated mydriasis. Lens opacity values showed a highly significant positive correlation to age. Serum cholesterol, systolic blood pressure and smoking habits showed no significant correlations to the levels of lens opacity when adjustments for age were made.Abbreviations HMG-CoA hydroxy-methylglutarylcoenzyme A - 4S Scandinavian Simvastatin Survival Study - LOM lens opacity meter     

Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media.

BACKGROUND: Atherosclerosis begins early in life. Infections might contribute to the pathogenesis of atherosclerosis. In this study, we investigated whether acute infections in children could alter the carotid wall morphology and the lipid profile. METHODS: Mean carotid intima-media thickness (IMT) was measured by high-resolution ultrasound in 28 hospitalised children (mean age: 5+/-2 years), who fulfilled the diagnostic criteria of acute infections (body temperature, >38 degrees C; C-reactive protein, >15mg/ml, and clinical), and in 20 age- and gender-matched controls. Antibodies against oxidised low-density lipoprotein (anti-oxLDL antibodies), as well as total and high-density lipoprotein cholesterol (HDL-C) were analysed in all children. The infection group was investigated both during the acute illness and 3 months after clinical recovery (post-infection). RESULTS: During the acute illness, the infection group had elevated anti-oxLDL antibodies and decreased HDL-C, as compared to those obtained at 3 months and in controls (p<0.05). These changes in the infection group were followed, at 3 months, by thickening of carotid intima-media. Those who received antibiotics during their acute illness had less carotid thickening than those who were not treated with antibiotics (p<0.05). CONCLUSION: Acute infections in children seem to be accompanied by enhanced oxidative modification of LDL and by decrease in HDL-C. These lipid changes may be followed by thickening of carotid artery intima-media. These findings suggest that, in childhood, acute infections could be associated with increased risk of atherosclerosis, and warrant further studies on this topic.     

从TNT研究看稳定性冠心病患者的强化降脂治疗

4 背景 强化降脂使低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）低于指南推荐的水平将使急性冠脉综合征患者获益。但强化降脂使稳定性冠心病患者的LDL-C低于100mg／dL是否安全和有效尚不清楚。     

ALTERATION OF CHOLESTEROL SULFATE IN HUMAN SERA DURING THE COURSE OF PREGNANCY

Objective To determine the concentrations of cholesterol sulfate ( CS) in human sera and pla-cental villi during the course of pregnancy. And to analyze its inhibitory activity on thrombin and further characterize the functional significance of CS. Methods The concentrations of CS were determined by thin-layer chromatog-raphy (TLC) on 60 cases of normal pregnant women and 30 cases of normal placental villi. The effect of CS in human sera on the activity of thrombin was analyzed. Results The concentrations of CS in human sera gradually increased from the first to third trimester of gestation with a correlation coefficient of 0. 69, and a correlation between the concentration of CS and weeks of gestation (P <0. 01). CS was also contained in the placental villi, and its concentrations at the second and third trimester of gestations were 4. 7 and 6. 2-fold of that at the first trimester of gestation. CS inhibited the activity of thrombin. Conclusion Placental CS is one of the sources of CS in the serum , pr