Association of serum low-density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children

The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10-15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when XI, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the XI/XI genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL-lowering effects of oestrogen occur through the ER (alpha) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.     

载脂蛋白E基因多态性与脑血管疾病的关系

目的探讨载脂蛋白E（ApoE）基因多态性与脑血管疾病（Cerebrovascular disease，CVD）的关系。方法应用聚合酶链式反应——限制性片断长度多态性（PCR—RFLP）技术检测CVD患者98例（脑梗死78例，脑出血20倒）和90名健康对照的ApoE基因多态性分布特征。应用酶比色法检测血脂水平。结果发现5种ApoE基因型，脑梗死组E3／4基因型频率（23．1％）及ε4频率（14．7％）显著高于对照组（7．8％，5．0％），而E3／3基因型频率（56．4％）及ε3频率（75．6％）显著低于对照组（78．9％，88．3％）。脑出血组的ApoE基因型及基因频率与对照组比较差异无显著性。不同ApoE基因型之间TC和LDL水平差异有统计学意义（P〈0．05）。结论发现ApoEε4基因是CI发病的遗传易患因子；而ApoEε3基因则对CI具有保护作用。同时ApoE基因多态性影响血脂水平。     

Lipid and apolipoprotein levels and enteral nutrition in very low-birth-weight preterm infants

Lipid, lipoprotein cholesterol and apolipoprotein A-I, A-II and B levels were determined in 10 very low-birth-weight (birth weight 1279 ±144 g; gestational age 29.2±1.2 weeks, mean ± SD) preterm infants on postnatal days 3, 10 and 21. Feeding with pooled human milk began on day 3 ± 1 and by day 10 all infants were exclusively enterally fed. Both triglyceride and total cholesterol levels increased significantly from day 3 to day 10 (0.84 ± 0.28 versus 1.53 ± 0.72 and 2.42 ± 0.47 versus 3.24 ± 0.80, mmol/l, respectively) ( p <0.01); thereafter no further increase was observed. The increase in total cholesterol level was primarily due to a significant enhancement of very low-density lipoprotein and low-density lipoprotein cholesterol (1.52±.34 versus 2.29 ± 0.73 mmol/l, p <0.01). Apo A-I, A-II and B levels did not change between day 3 and day 10. From day 10 to day 21, however, a significant increase in apo A-I concentration was noted (0.57±.20 versus 0.87 ± 0.17 g/l, p <0.01), whereas apo A-II levels increased significantly from day 3 to 21 (0.15 ± 0.03 versus 0.27 ± 0.08 g/l, p<0.01). No change in apo B level was seen.     

Apolipoprotein C-ll deficiency syndrome due to apo C-IIHamburg: clinical and biochemical features and Hphl restriction enzyme polymorphism

We have characterized the clinical and biochemical features of three siblings of a kindred with severe hypertriglyceridaemia due to apolipoprotein C-II (apo C-II) deficiency caused by the mutation described as apo C-IIHamburg. The clinical syndrome is characterized by recurrent pancreatitis in two of three affected individuals, with discrete hepatosplenomegaly in all three patients and cholelithiasis in one. Eruptive xanthomas and lipemia retinalis were absent. Plasma lipoproteins were characterized by fasting chylomicronaemia, reduced low density lipoproteins (LDL) and low high density lipoproteins (HDL). The marked hypertriglyceridaemia could be corrected promptly by infusion of normal plasma. Apolipoprotein C-II (apo C-II) levels in homozygotes were very low (0.01 mg dl-1), and mean apo C-II levels in heterozygotes were lower (2.08 +/- 0.11 mg dl-1) than in normal family members (3.38 +/- 0.75 mg dl-1). Lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma were normal. Zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins and reduced LDL and HDL. LDL consisted of two fractions with higher hydrated density of the main fraction compared with normals with a trend to normalization on a fat-free diet. The molecular defect in the apo C-II Hamburg gene has been previously identified as a donor splice site mutation in the second intron. This leads to abnormal splicing of the apo C-II Hamburg mRNA and apo C-II deficiency in plasma. The mutation causes the loss of an HphI restriction enzyme site present in the normal apo C-II gene.(ABSTRACT TRUNCATED AT 250 WORDS)     

雌二醇对雌性大鼠血清载脂蛋白AI和B含量的影响

为观察雌二醇对大鼠血清载脂蛋白AI和B含量的影响，用免疫比浊法和放射免疫分析法检测了性周期雌性大鼠、去卵巢大鼠和去卵巢注射雌二醇大鼠的血清雌二醇、载脂蛋白AI和B的水平。结果发现，在大鼠性周期中，血清雌二醇与载脂蛋白AI水平均呈周期性波动，两者的变化趋势一致。大鼠卵巢摘除后15天，血清雌二醇与载脂蛋白AI含量较未摘除卵巢大鼠显著降低（分别为0．82±0．32ng／L和0．51±0.11g／L），而注射雌二醇大鼠两者的含量又明显增加（分别为116．94±38．91ng／L和1．80±0．21g／L，P＜0.01）。但是，在性周期中、摘除卵巢和注射雌二醇大鼠血清中载脂蛋白B的含量无明显变化。提示，雌二醇可能调节雌性大鼠血中载脂蛋白AI的含量。     

慢性肾功能不全患者血浆载脂蛋白A_1、B浓度变化的临床观察

研究了慢性肾功能不全(CRI)患者血浆载脂蛋白A_1、B浓度与肾功能的关系。方法:将45例CRI患者按肾功能分为3组,检测其血浆apoA_1和apoB浓度,并与健康对照组比较。结果:CRI患者的血浆apoA_1浓度显著低于对照组(P<0.01),且肾功能越低,降低越显著(P<0.01),apoB浓度及apoB/apoA_1,显著高于对照组(P<0.01),且肾功能越低,升高越显著(P<0.01)。结论:CRI患者存在动脉硬化倾向,且随肾功能减退加重,这种倾向更加明显。     

Neural stem cell grafts reduce the extent of neuronal damage in a mouse model of global ischaemia

The therapeutic potential of neural stem cell transplantation has been well demonstrated in many models of focal brain damage. However, few studies have sought to determine whether neural stem cells are therapeutic in models of diffuse brain injury, such as observed in Alzheimer's disease and global ischaemia. The present study investigated the effects of transplanted MHP36 neural stem cells on the extent of ischaemic damage in a mouse model of global ischaemia and the effects of the immunosuppressive agent cyclosporin A (CsA). C57Bl/6J mice received an intrastriatal graft of MHP36 neural stem cells 3 days after selective neuronal damage had been induced by global ischaemia. The experimental group was subdivided into CsA or saline controls. We discovered that grafts of MHP36 neural stem cells were able to differentiate into neurons and reduce the extent of ischaemic neuronal damage. This reduction was particularly apparent at 4 week post-transplantation and is independent of CsA immunosuppression. MHP36 cells survived robustly in host ischaemic brain and migrated away from the injection tract towards the caudate nucleus and corpus callosum. Although MHP36 grafts were associated with an acute inflammatory response from reactive astrocytes and microglia at 1 week post-transplantation, this decreased markedly by 4 weeks post-transplantation even in the absence of CsA immunosuppression. This is the first study showing a therapeutic benefit of neural stem cells in a highly diffuse brain injury, further highlighting the possibilities of stem cell transplantation for all types of neurodegenerative disease.     

Peripheral inflammatory and fibrinolytic markers in adolescents with growth hormone deficiency: relation to postprandial dyslipidemia

OBJECTIVE: To determine whether peripheral inflammatory and fibrinolytic markers are elevated in growth hormone-deficient (GHD) adolescents and associated with increased postprandial lipoproteins. STUDY DESIGN: Fifteen GHD children on GH treatment with a chronologic age of 12.7 +/- 2.5 years and 10 untreated GHD adolescents with a chronologic age of 13.0 +/- 2.6 years were studied. Triglycerides (TG), C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured in the fasting state and 4 hours after ingesting a high-fat meal; 15 healthy adolescents served as controls. RESULTS: Fasting and postprandial TG of untreated GHD children were higher than those in treated subjects and healthy controls. Fasting TNF-alpha, CRP, and fibrinogen concentrations of untreated GHD adolescents were higher than those in healthy controls, but similar to those of GH-treated GHD adolescents. Although fibrinogen levels increased after a high-fat meal in GHD adolescents, CRP, TNF-alpha, and IL-6 concentrations did not increase further. Fasting and postprandial TG of untreated GHD adolescents were positively associated with fasting and postprandial CRP, and with postprandial TNF-alpha and IL-6 concentrations. Fasting TG also correlated positively with fasting fibrinogen concentrations in untreated and treated GHD adolescents. CONCLUSIONS: The pronounced inflammatory response seen in GHD adolescents seems to be associated with the presence of elevated levels of fasting and postprandial TG, which may result in an increased susceptibility for premature atherosclerosis.