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.     

β-血小板球蛋白对小牛主动脉内皮细胞的LDL受体活性的抑制作用的初步研究

本文首次报告了β-血小板球蛋白(β-TG)能明显抑制小牛主动脉内皮细胞的LDL受体活性,但不影响该受体的生成。初步分析提示β-TG的这种抑制作用可能不完全是由于β-TG和~(125)I-LDL之间存在的竞争性抑制作用所致。此外,对于β-TG的这种抑制作用在动脉粥样硬化形成中的意义进行了讨论。     

Oxidatively modified LDL particles in the human placenta in early and late onset intrauterine growth restriction

Introduction

Reduced serum LDL concentrations have been observed in pregnancies complicated by intrauterine growth restriction (IUGR) as compared to healthy pregnant women. Since increased oxidative stress has been suggested to play a major role in IUGR we now hypothesized that the lower LDL concentrations are accompanied by an accumulation of oxidized LDLs in the placenta.

Methods

Fifteen placentas of near term and preterm born IUGR, and a gestational age matched control group (CTRL n = 15) were analyzed. Placental minimal modified LDL and fully oxidized LDL particles were measured by ELISA, and by immunohistochemistry, and were related to maternal and fetal serum lipid profiles.

Results

We found fully oxidized LDL but not minimal modified LDL being increased in the preterm subgroup of IUGR (n = 10) as compared to preterm CTRL (n = 10; p < 0.05). An increased staining intensity of trophoblasts in preterm IUGR subjects as compared to preterm CTRL has been confirmed by immunohistochemistry (p < 0.05). No difference could be found between the term groups (n = 5 each). Correlation analysis revealed an inverse relationship of maternal LDL (ρ = −0.49, p = 0.03) and fetal HDL cholesterol (ρ = −0.46, p = 0.04) with placental fully oxidized LDL particle concentration within preterms.

Discussion

IUGR is a heterogeneous entity. Different pathomechanisms seem to underlie the disease in preterm and term subjects with oxidation of LDL within the placenta possibly taking place in preterm IUGRs.

Conclusions

We conclude that the reduced maternal LDL cholesterol concentration in IUGR pregnancies is attributed to increased accumulation of oxidized LDL particles within the placenta at least in early onset IUGR.     

Leptin and paraoxonase activity in cord blood from obese mothers

Abstract

Objective: Obesity and/or psychopathological disorders of parents represent risk factors for childhood obesity. The aim of the study was to investigate the link between obesity in pregnancy and oxidative stress.

Methods: Venous blood was collected from 37 women at the eighth month of gestation (19 obese and 28 normal weight). Cord blood was obtained at birth from newborns of obese mothers and controls. Cord blood and maternal blood was used to separate plasma to be used for the evaluation of leptin, oxidized LDL and paraoxonase (PON1) activity.

Results: Higher levels of leptin were observed both in maternal blood and cord blood of children of obese women compared to normal-weight women. The data also showed lower levels of PON1 activity in plasma of obese women and in the cord blood of their children. Furthermore, a positive correlation was established between levels of PON1 activity in maternal blood and cord blood, suggesting a relationship between PON1 in maternal plasma and fetal cord blood.

Conclusions: Essential obesity in pregnancy is associated with hyperleptinemia. PON1 exerts an antioxidant role; therefore, our results demonstrated that obesity exposes to an increased susceptibility to oxidative damage in both mothers and newborns.     

Oxidized-low density lipoprotein in gingival crevicular fluid of patients with chronic periodontitis: a possible link to atherogenesis

Objective. To investigate a possible link between periodontitis and atherogenesis by examining the levels of anti-oxidized low density lipoprotien (ox LDL) and low density lipoprotien (LDL) in gingival crevicular fluid (GCF) and serum of healthy subjects and chronic periodontitis patients. Methods. Sixty male subjects (35–55 years) were grouped into 30 healthy individuals and 30 subjects with chronic periodontitis. Serum and GCF samples were obtained from each subject and were assessed for anti-ox LDL and LDL levels. Results. A significant difference (p < 0.001) was found between the anti-ox-LDL levels in GCF of healthy vs chronic periodontitis groups. Also the ratio of GCF anti-ox LDL to GCF LDL was significantly higher (p < 0.001) in chronic periodontitis patients as compared to the healthy group. Conclusions. A significant rise in ox LDL level in otherwise systemically healthy chronic periodontitis patients may put these subjects at an increased risk of developing atherosclerosis.     

Relationship of low-density lipoprotein and nephrolithiasis in different genders

Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study. Methods All participants were investigated by questionnaires, physical examinations and laboratory tests including liver and renal function, lipid profile, serum fasting glucose, glycosylated hemoglobin. Nephrolithiasis was diagnosed by kidney B-ultrasonography. Subjects with estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1 were excluded. Results 10 316 individuals were enrolled with an average age of (54.88±10.27) years (range 17-88 years) and the ratio of male to female 1∶1.12. The prevalence of nephrolithiasis was 5.6%, 3.7% and 7.8% for whole population, women and men, respectively. In women, only eGFR in stone group was significantly lower than that in non-stone group (P＜0.05). However, participants in stone group were significantly older (P＜0.05), of higher blood pressure (P＜0.01), higher serum uric acid (P＜0.01), worse renal function (serum creatinine, P＜0.05; eGFR, P＜0.01), and higher low-density lipoprotein (LDL) (P＜0.05), compared with those in non-stone group in men. Logistic regression analysis showed that only eGFR (P＜0.05) was the independent influential factor for kidney stones in women; In men, LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95%CI 1.003-1.317, P＜0.05), except for mean blood pressure and eGFR. After being divided into normal group, borderline high group and high LDL group according to the LDL level, with the increase of LDL, the prevalence of nephrolithiasis was significantly increased by 7.3%, 8.3% and 10.6% in men respectively. There was no significant relationship between total cholesterol, triglyceride, high-density lipoprotein and nephrolithiasis. Conclusions Dyslipidemia is associated with nephrolithiasis in men, and high LDL cholesterol is an independent risk factor for nephrolithiasis. Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease, but also reduces the risk of kidney stones.     

Perfil lipídico em pacientes adultos com artrite idiopática juvenil

The inflammatory processes in the joints of a child with juvenile idiopathic arthritis (JIA) can persist into adulthood. Inflammation has been linked to distortions of the lipid profile and accelerated atherogenesis. In the present study, we examined the lipid profiles of adults with JIA compared with those of healthy people. A lipid profile of a sample of 54 adults with JIA (57.3% with polyarticular JIA, 37.0% with oligoarticular JIA, 1.9% with enthesitis-related JIA and 3.7% with systemic onset JIA) and 54 healthy subjects were compared. In the adults with JIA, data on gender, age, age at disease onset, the presence of rheumatoid factor (RF) and antinuclear antibodies (ANA), a Health Assessment Questionnaire (HAQ) and the disease duration were collected. We found that hypercholesterolaemia, increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) were more common in patients with JIA than the controls (P = 0.016, P < 0.0001 and P = 0.0008, respectively). Changes in the levels of total cholesterol (TC) and LDL were more common in the individuals who had a later onset of disease (P = 0.0017 for TC and P = 0.023 for LDL). In the entire JIA group, no other variable, such as RF, ANA, disease duration or responses to the HAQ, could be linked to dyslipidaemia (P = non-significant). We concluded that the adult patients with JIA have a lipid profile with increased TC and LDL levels and decreased levels of HDL compared to the controls. No clinical feature could be correlated with this change except for the age at disease onset.     

DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level

A strong association has been uncovered between DNA variation at the apolipoprotein B (apoB) locus (detectable with the restriction endonuclease XbaI) and apoB level. The findings are suggestive of associations also between this DNA polymorphism and total cholesterol as well as fasting triglyceride levels, confirming recent results reported by British workers. The data suggest that lipid/apolipoprotein associations with the XbaI polymorphism are primarily caused by an effect on apoB level. In the present and in a previously reported study we found a strong association between the XbaI polymorphism and the homospecific Ag antigenic variation in low density lipoprotein (LDL) which had previously exhibited associations with lipid levels. The present data indicate that the apoB/lipid associations of the Ag and XbaI polymorphisms may reflect the same phenomenon. The associations reported could reflect variation in an apoB domain close to Ag as well as to the XbaI restriction site that is of importance for lipid binding by apoB. Alternatively, the association of apoB level with the XbaI polymorphism (which reflects a silent third base mutation in a threonine codon) could reflect phenomena related to codon usage.     

低密度脂蛋白受体基因多态性对血脂康调脂疗效的影响

探讨低密度脂蛋白受体(LDLR)基因Hinc Ⅱ酶切位点多态性对血脂康调脂疗效的影响。高脂血症患者血清总胆固醇(TC)≥5.20mmol/L和(或)三酰甘油在2.00～5.65mmol/L之间者,共66例,随机分为血脂康组和安慰剂组,每组33例。根据LDLR基因Hind Ⅱ酶切多态性分层比较血脂康和安慰剂的调脂疗效,发现血脂康组H1H1和H1H2基因型患者的总胆固醇或低密度脂蛋白胆固醇(LDLC)下降的有效率(TC和LDLC分别下降≥10%),均明显低于H2H2基因型者(P均＜0.05);H1H1和H1H2基因型的TC或LDLC下降幅度亦均明显低于H2H2基因型者(TC依次平均下降17.1%、20.6%和29.0%,LDLC依次平均下降19.5%、25.0%和33.9%,P均＜0.05)。说明具有h1等位基因的高脂血症患者对降低胆固醇治疗药物血脂康的反应较差,而h2等位基因反应较为敏感。安慰剂组未发现上述现象。提示LDLR Hinc Ⅱ酶切位点间接参与了人体内胆固醇代谢和(或)血脂康控制血清胆固醇的重要环节。     

运动超负荷与压力超负荷大鼠血浆HDL、LDL变化的比较研究

在ＳＤ大鼠运动超负荷和压力超负荷模型上,采用ＲＭ—６０００型多导生理记录仪,ＢＥＣＫＭＡＮ４２型自动生化分析仪对大鼠体重、血压、心率、高密度脂蛋白（ＨＤＬ）和低密度脂蛋白（ＬＤＬ）等指标进行了测定。结果表明,一般运动负荷组体重增加,心率降低、血压恒定,ＬＤＬ显著性降低（ｐ＜０．００１）,ＨＤＬ显著性升高（ｐ＜０．０１）;运动超负荷组体重显著性降低,心率增加,血压上升,ＬＤＬ升高,ＨＤＬ显著性降低（ｐ＜０．０１）;压力超负荷组体重、心率增加,血压呈高血压指标,ＬＤＬ升高显著（ｐ＜０．０１）,ＨＤＬ降低显著（ｐ＜０．００１）。上述结果表明,一般运动负荷可使机体血压恒定,心率减慢,血脂代谢水平改善,运动超负荷可使机体体重下降,心率、血压升高,血脂代谢水平异常,并与高血压型相似,对维持健康水平不利