Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder,post-traumatic stress disorder comorbid with major depressive disorder,or major depressive disorder

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related post-traumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.     

一种LDL吸附剂载体-聚丙烯酰胺微球的合成及应用

研究用于低密度脂蛋白 (L DL)吸附的聚丙烯酰胺微球载体的合成工艺、结构特性及吸附 L DL 的性能 ,为进一步研发 L DL 吸附剂载体提供实验依据。采用反相悬浮聚合法按一定的配方合成聚丙烯酰胺微球载体 ,通过扫描电镜、图像分析仪、X光小角散射等手段对其结构特性 (粒径、孔径等 )进行表征 ;同时在微球上固定丝氨酰 -天冬氨酰 -谷氨酸 (SDE)三肽配体制成 L DL 吸附剂 ,通过体外静态吸附对其吸附性能进行了初步研究。结果表明微球粒径为 14 2 .1μm,孔径为 119.8nm,符合作为 L DL 吸附载体的需要 ;在交联剂与单体总量一定的条件下 ,微球孔径随着交联剂用量的增加而减小 ;合成的聚丙烯酰胺微球对 L DL 的非特异性吸附很小 ,而在其上偶联配体制成吸附剂后 ,又表现出对 L DL 的特异性吸附。本实验合成的聚丙烯酰胺微球是一种有效的 L DL 吸附剂载体。     

Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial hypercholesterolemia in Spain

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis of Bgt II digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls. Hindi, Avail, Pvu II, Msp I, and Nco I are the most polymorphic sites with individual PIC values higher than 0.28, whereas the Taq I and Stu I sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH-families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B-100 (FDB) due to the apoB₃₅₀₀ mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populations.     

三磷酸腺苷结合盒转运体A1在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的作用

目的:以THP-1巨噬细胞源性泡沫细胞为研究对象, 探讨ABCA1在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的作用。方法:用液体闪烁计数器检测胆固醇流出。RT-PCR方法检测ABCA1mRNA的表达。结果:氧化型低密度脂蛋白可增加THP-1巨噬细胞胆固醇流出, 22(R)-羟基胆固醇剂量依赖性增加THP-1巨噬细胞源性泡沫细胞胆固醇流出, 而DIDS剂量依赖性减少THP-1巨噬细胞源性泡沫细胞胆固醇流出;逆转录聚合酶链反应显示, 22(R)-羟基胆固醇可增加THP-1巨噬细胞源性泡沫细胞ABCA1mRNA的表达, DIDS可抑制THP-1巨噬细胞源性泡沫细胞ABCA1mRNA的表达。结论:ABCA1在巨噬细胞源性泡沫细胞胆固醇流出中起着重要的作用, 并为开发和寻找对ABCA1表达有特异性调控作用的药物提供了新的思路。     

Normal human IgG prevents endothelial cell activation induced by TNFalpha and oxidized low-density lipoprotein atherogenic stimuli

Normal human immunoglobulin G (IgG) has anti-inflammatory and immuno-regulatory properties, which are exploited in the therapy of selected diseases. A putative mechanisms of action is the direct regulation of endothelial cell function by natural antiendothelial cell antibodies. Endothelium activation is a critical event in atherosclerosis. We have verified the ability of normal human IgG to modulate endothelial responses to the atherogenic stimuli tumour necrosis factor-alpha (TNFalpha) and oxidized low-density lipoproteins (oxLDL) in vitro. Confocal microscopy was used to visualize vascular cell adhesion molecule-1 (CD106) expression on endothelial cells, cytoplasmic free calcium ([Ca++]i) modifications and fluorescein-coupled oxLDL internalization. Cytokine secretion was measured by ELISA on cell supernatants. IgG prevented TNFalpha induced CD106 membrane expression and an increase in [Ca++]i, and inhibited the secretion of interleukin-6 (IL-6) and macrophage-colony-stimulating factor (M-CSF). IgG also inhibited CD106 expression induced by oxLDL and one pathway of their internalization, but were ineffective on oxLDL induced [Ca++]i rise and apoptosis. F(ab)'2 fragments from IgG, but not monoclonal IgG, reproduce IgG effects. These findings point to a regulatory role for specific antibodies included in circulating normal IgG towards proinflammatory responses of endothelial cells in atherogenesis and suggest possible development of new therapeutic strategies.     

LDL-ACM复合物对裸鼠皮下移植瘤靶向抑制作用的初步研究

目的: 通过观察比较LDL-ACM复合物和游离ACM对胃癌SGC-7901,NKM-45细胞株裸鼠皮下移植的抑制效应,从而了解LDL作为抗癌药物靶向载体的应用价值。方法: 首先采用温育交换法制备LDL-ACM复合物,然后建立人胃癌细胞株裸鼠皮下移植瘤模型,以瘤重、肿瘤体积、白细胞计数、抑瘤率、生命延长率等指标观察LDL-ACM对移植瘤的抑制作用。结果: LDL-ACM组的移植瘤生长速度明显慢于生理盐水组及游离ACM组,抑瘤率和生命延长率明显高于生理盐水组及游离ACM组,外周白细胞计数无明显变化,尤其对SGC-7901瘤更为明显。结论: LDL-ACM复合物与游离ACM相比有更强的抑癌效应。LDL-ACM复合物有可能是通过LDL受体介导起作用。     

A comparative study between the effect of 17-β estradiol and antioxidants combination on some menopausal changes in oophorectomised rats

BackgroundAs oxidative stress is proposed to be responsible for many of the menopause associated disorders, antioxidants may play an important role in this situation. The aim of this work was to compare between the effects of oestrogen replacement therapy and antioxidant supplements of vitamin C and low dose of vitamin A on some menopause associated changes in oophorectomised rats.Materials and methodsForty albino female rats were divided into 4 groups: normal control group, oophorectomised group, oophorectomised group treated with 17-β estradiol (oophorectomised + E₂) and oophorectomised group treated with vitamins (oophorectomised + vit).The following were measured: total antioxidant (TAO) and malondialdehyde (MDA), lipid profile, serum insulin, glucose and homeostasis model assessment-insulin resistance (HOMA-IR), bone specific alkaline phosphatase (BALP), urinary hydroxyproline, weight gain and visceral fat.ResultsA positive correlation was found between MDA and low density lipoprotein-cholesterol (LDL) (r = 0.694 and P = 0.000), HOMA-IR (r = 0.691 and P = 0.000.) and BALP (r = 0.563 and P = 0.000) and urinary hydroxyproline level (r = 0.761 and P = 0.000). Those results denoted that OS might be a cause of dyslipidemia, insulin resistance and osteoporosis associated with menopause.Both E₂ and vitamins in oophorectomised rats led to a significant decrease in MDA (F = 33.402, P = 0.000), weight gain, visceral fat (F = 7.589, p = 0.000 and F = 3.748, P = .019, respectively), cholesterol (F = 40.748, P = 0.0001), LDL cholesterol (F = 55.168, P = 0.0001), and significant increase in HDL (F = 18.393, P = 0.0001) and TAO levels (F = 14.781, P = 0.000) compared to oophorectomised rats. Also, both treatments led to a significant decrease of HOMA-IR (F = 18.933, P = 0.000, respectively), BALP (F = 13.202, P = 0.000) and urinary hydroxylproline (F = 220.012, P = 0.000). An interesting finding was detected where oophorectomised rats showed a decrease in triglyceride level which was significantly increased by E₂ administration whereas antioxidant administration produced no change (F = 34.267, P = 0.0001).ConclusionOur results denote similar effects of both E₂ and antioxidant’ supplements (vitamin C and low dose vitamin A) administration in surgically induced menopause in rats regarding oxidative stress, weight gain, atherogenic lipid profile changes, insulin sensitivity and bone turnover. However differences between preclinical and clinical studies must be taken into consideration especially when moving from animal studies to clinical trials.     

Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia

We used the denaturing gradient gel electrophoresis (DGGE) method to investigate 120 Japanese patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequence of the low density lipoprotein (LDL) receptor gene. Fourteen aberrant DGGE patterns were found, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations (C317S, F382L A410T, L547V, and E693K), two nonsense mutations (W512X and K790X), four frameshift mutation (355del7, 1246ins5, 1687ins1, and 2035ins1), one splicing mutation (1845+2 T→C), and two inframe mutations (661ins21 and 1115del9/ins6) were identified. Six of these mutations (L547V, E693K, W512X, 355del7, 1687ins1, and 20354ins1) have not been described before in FH. These newly identified mutations cosegregated in their family members with defective LDL receptor activity and hypercholesterolemia, and are thought to be causal for the FH phenotype. These results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Japanese population. Hum Mutat 14:87, 1999. © 1999 Wiley‐Liss, Inc.     

氧化修饰和乙酰修饰低密度脂蛋白在A型清道夫受体基因敲除小鼠的清除

目的：阐明清道夫ＡＩ／Ｉ受体（ＳＲ－ＡＩ／Ｉ）在体内ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ清除中的作用和重要性。方法：观察同位素标记化学修饰ＬＤＬ在ＳＲ－ＡＩ／Ｉ基因敲除和正常小鼠血浆的清除率和同位素标记的ＬＤＬ在体内主要器官的分布。结果：ＯＸ－ＬＤＬ在正常小鼠血浆清除是非常快的,在５ｍｉｎ内,注入量的９０％即被清除。在ＳＲ－ＡＩ／Ｉ基因敲除小鼠,ＯＸ－ＬＤＬ在血浆的清除速率和正常小鼠相同。ＡＣ－ＬＤＬ的清除在对照组和ＳＲ－ＡＩ／Ｉ受体敲除小鼠也相似。同位素标记的ＡＣ－ＬＤＬ在血浆的清除能够完全被５０倍高剂量未标记的ＡＣ－ＬＤＬ阻断,但同样剂量的未标记的ＡＣ－ＬＤＬ仅能抑制ＯＸ－ＬＤＬ在血浆清除的５％。ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ主要被肝脏清除。组织器官放射性标记的ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ的分布在正常小鼠和ＳＲ－ＡＩ／Ｉ基因敲除小鼠没有差异。结论：ＳＲ－ＡＩ／Ｉ受体在体内ＯＸ－ＬＤＬ清除过程中不起主要作用。