Adipocyte factors,high-sensitive C-reactive protein levels and lipoxidative stress products in overweight postmenopausal women with normal and impaired OGTT

Objective

In obese postmenopausal women we assessed leptin and adiponectin, high-sensitive C-reactive protein (hsCRP), serum lipids and lipoxidative stress products: oxidized LDL (oxLDL) and malondialdehyde (MDA), in relation to impaired glucose tolerance (IGT).

Methods

Thirty-eight overweight/obese postmenopausal women were included in the study. Eighteen with normal glucose metabolism (NGT) and twenty with IGT, as it is diagnosed by OGTT. Serum leptin, adiponectin, hsCRP and MDA were measured at time 0 and 120 min of OGTT while total-cholesterol, LDL, HDL, triglycerides, oxLDL and anti-oxLDL autoantibodies at time 0. Insulin resistance (HOMA)/sensitivity (QUICKI) indexes were estimated.

Results

In subjects with NGT, hsCRP was positively correlated with fasting leptin and HOMA, while in subjects with IGT negatively with QUICKI. In both groups, hsCRP was positively correlated with fasting insulin, body mass index and waist circumference. Fasting adiponectin was positively associated with HDL in both groups and negatively with triglycerides in subjects with NGT as well as with serum glucose levels at time 120 min of OGTT in subjects with IGT. No association was observed between oxLDL and adipokines. A significant positive association was found between oxLDL and HOMA in subjects with IGT. During OGTT there was a significant increase of leptin and MDA levels in both groups.

Conclusions

A relationship exists between obesity, insulin and sub-clinical inflammation. Leptin and lipid peroxidation are linked to hyperglycaemic state while oxLDL might be considered as a predictor of insulin resistance. Adiponectin could exert its antiatherogenic effect through HDL independently of the presence of IGT.     

缺血预适应对青年与老年大鼠缺血/再灌注心肌氧化应激及线粒体功能的影响

目的:探讨缺血预适应(ischemic preconditioning,IPC)对青年与老年大鼠缺血/再灌注(ischemia/reperfusion,IR)心肌损伤的影响。方法:雄性3月龄(青年)与20月龄(老年)Wistar大鼠,应用离体心脏灌流方法复制心肌IR与IPC模型。实验分为青年缺血/再灌注(YIR)组、青年缺血预适应(YPC)组、老年缺血再灌注(OIR)组与老年缺血预适应(OPC)组。透射电镜观察心肌及心肌线粒体超微结构变化;TTC染色测定心肌梗死面积;比色法测定冠脉流出液中乳酸脱氢酶(LDH)活性、心肌组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;酶联免疫吸附法测定心肌组织硝基化与羰基化蛋白质含量,TUNEL方法检测心肌细胞凋亡;氧电极法测定线粒体呼吸功能及钙诱导的线粒体渗透性转运孔开放情况。结果:与YIR组比较,YPC组心肌梗死面积明显减少,冠脉流出液中LDH活性降低,心肌组织的SOD活性增加,MDA含量降低,心肌硝基化与羰基化蛋白含量降低。电镜下可见YPC组心肌及分离的心肌线粒体膜结构完整、基质致密。YIR组心肌线粒体呼吸控制率与Ⅲ态耗氧量及P/O比值均明显增加,质子漏出减少,钙诱导的线粒体肿胀明显减轻,心肌细胞凋亡率下降。而与OIR组比较,OPC组上述指标均无显著统计学差异。与YPC组比较,OPC组心肌超微结构损伤明显增加,心肌氧化应激水平增加,线粒体呼吸功能下降,心肌细胞凋亡与坏死增多。结论:缺血预适应能够保护青年大鼠心肌缺血/再灌注损伤;而老年大鼠心脏对预适应刺激减敏,导致缺血预适应心肌保护作用钝化,这可能与老龄IPC心脏氧化应激水平增加导致线粒体损伤、细胞凋亡有关。     

自然流产妇女血清氧化应激状态分析

目的通过对自然流产女妇血清氧化应激指标———超氧化物歧化酶(SOD)、丙二醛(MDA)及维生素E(VE)的测定,分析其氧化应激状态。方法用化学比色法对20例正常未孕妇女、20例正常孕早期妇女及20例自然流产妇女血清中SOD、MDA及VE进行测定。结果与未孕妇女相比,正常孕早期妇女血清MDA升高(P<0.05),SOD和VE也显著升高(P<0.05;P<0.05);与正常孕早期妇女相比。自然流产妇女血清MDA水平升高(P<0.05),SOD、VE水平却下降(P<0.05;P<0.05)。结论自然流产妇女处于氧化应澈状态中。     

Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure levels in patients with essential hypertension

High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the development of coronary artery disease. In vitro experiments have shown that oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation, thus suggesting a possible role of Lp(a) in the genesis of essential hypertension. The aim of our work was to investigate the correlation of blood pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and peroxidative stress in patients with essential hypertension. The study was performed in 54 untreated hypertensive patients whose blood pressure was monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration was measured by a double monoclonal antibody-based enzyme immunoassay demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were determined by a high-resolution SDS-agarose gel electrophoresis followed by immunoblotting. A significant correlation was found between Lp(a) levels and the night-time systolic and diastolic pressures (r=0.32, P<0.05, and r=0.30, P<0.05, respectively), as well as with the mean night-time fall in systolic and diastolic blood pressures (r=0.28, P<0.05 and r=0.29, P<0.05, respectively). These relationships were further potentiated when peroxidative stress data were taken into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and diastolic pressures, respectively and r=0.34 and r=0.38, P<0.01 for the night-time fall in systolic and distolic blood pressures, respectively). Apo(a) isoform size did not affect these relationships. Our data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated. Received: 16 July 2001 / Accepted: 15 September 2001     

The role of epidermal growth factor in prevention of oxidative injury and apoptosis induced by intestinal ischemia/reperfusion in rats

Intestinal ischemia/reperfusion is a major problem which may lead to multiorgan failure and death. The aim of the study was to evaluate the effects of epidermal growth factor (EGF) on apoptosis, cell proliferation, oxidative stress and the antioxidant system in intestinal injury induced by ischemia/reperfusion in rats and to determine if EGF can ameliorate these toxic effects. Intestinal ischemia/reperfusion injury was produced by causing complete occlusion of the superior mesenteric artery for 60 min followed by a 60-min reperfusion period. Animals received intraperitoneal injections of 150 μg/kg human recombinant EGF 30 min prior to the mesenteric ischemia/reperfusion. Mesenteric ischemia/reperfusion caused degeneration of the intestinal mucosa, inhibition of cell proliferation, stimulation of apoptosis and oxidative stress in the small intestine of rats. In the ischemia/reperfusion group, lipid peroxidation was stimulated accompanied by increased intestinal catalase and glutathione peroxidase activities, however, glutathione levels and superoxide dismutase activities were markedly decreased. EGF treatment to rats with ischemia/reperfusion prevented the ischemia/reperfusion-induced oxidative injury by reducing apoptosis and lipid peroxidation, and by increasing antioxidant enzyme activities. These results demonstrate that EGF has beneficial antiapoptotic and antioxidant effects on intestinal injury induced by ischemia/reperfusion in rats.     

Human SA gene polymorphisms are associated with non-high-density lipoprotein cholesterol in postmenopausal women: A pilot study

Objective

The purpose of the study is to evaluate the associations between polymorphisms of the human SA (SAH) gene, an acyl-CoA synthetase gene, with dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal women.

Methods

One hundred and forty-two postmenopausal women were recruited for the study. Each subject received anthropometric and blood pressure measurements, fasting sampling for lipids, and a 75-g oral glucose tolerance test for insulin resistance. Genotypes of two polymorphisms in the promoter region (c.-962ins/del, c.-451G > A), one missense variant (c.1077G > C, p.K359N) in exon 8, and one in intron 12 (A > G) of the SAH gene, were determined.

Results

There were significant differences in genetic distribution of the SAH gene promoter I/D polymorphism between the two groups of subjects by non-high-density lipoprotein cholesterol (non-HDL-C) levels (p = 0.004). The subjects with the DD genotype was associated with high levels of non-HDL-C (>160 mg/dL) as compared with the ID or II genotypes (p = 0.002). Furthermore, three haplotypes were constructed based on the promoter I/D and the exon 8 G/C polymorphisms. Homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the post menopausal women. The subjects with haplotype 3 had double the risk to have higher non-HDL-C levels than those with haplotype 1.

Conclusion

Our results suggest that the polymorphisms of the SAH gene are associated with non-HDL-C levels in postmenopausal women. Further studies with larger sample sizes or different populations are warranted to confirm our preliminary findings.     

Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis

PURPOSE: This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. METHODS: This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. RESULTS: bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. CONCLUSIONS: The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.     

Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model

Infection by different strains of influenza virus presents different pictures. Whether the pathogenicity of influenza virus is defined by the ability of the virus to induce differential immunopathlogical responses in the lungs still remains unclear. We compared the immunopathological response induced by influenza virus A/WSN/33 (H1N1) and that by A/Panama-like (H3N2) virus in C57BL/6 mice. WSN virus, in contrast to Panama-like virus, induced high mortality and severe lung pathology accompanied by massive Gr-1⁺ and CD11b⁺ cell infiltration and high levels of CXCL6/GCP-2, CCL2/MCP-1 and TIMP-1 production. Infection by WSN virus but not by Panama-like virus induced up-regulation of the active and latent forms of MMP-9 in the lungs and MMP-2/9 inhibitor partially reduced WSN virus-induced lung pathology. Both Gr-1⁺ and CD11b⁺ cells in WSN virus-infected lungs produced reactive oxygen and nitrogen species (ROS/RNS). While wild type mice infected by WSN virus had severe lung pathology and the presence of oxidized phospholipids and numerous MMP-9⁺ cells in the lungs, ncf1 deficiency ablated their expression and manifested less lung pathology. Employing a pulmonary mouse model we demonstrated in this study that infection by virulent influenza virus is characterized by a heavy cellular infiltration, severe lung pathology which is accompanied by oxidative stress and MMP-9 production.     

Beneficial effects of pravastatin in peri- and postmenopausal hyperlipidemic women: a 5-year study on serum lipid and sex hormone levels

Objectives: The aims of the present study are to assess the 5 year effects of pravastatin on serum lipids and lipoproteins in women around the menopause and to assess the effects of pravastatin on serum gonadotropins and sex steroid levels over a long-term period. Methods: We evaluated the long-term efficacy of pravastatin on serum lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride) in 121 patients (47 premenopausal and 74 postmenopausal women) suffering from primary hypercholesterolemia. The effects of this lipid-lowering drug on serum gonadotropins and sex steroids (estradiol, estrone, and testosterone) are also reported. Results: Pravastatin produced a remarkable reduction in the serum total cholesterol level of 19.2±9.3% (P<0.0001) and 18.9±11.8% (P<0.0001), and in LDLl-cholesterol of 25.1±18.7% (P<0.0001) and 24±18.0% (P<0.0001) after 24 and 60 months’ treatment, respectively. In hypertriglyceridemia, pravastatin also produced a remarkable reduction in triglyceride of 29.3±27.3% (P<0.0001) and 39.9±20.4% (P<0.0001) after 24 and 60 months of treatment, respectively. We found that serum gonadotropins and sex steroid levels changed naturally as a function of age from pre-therapy levels in the premenopausal patients after 60 months of treatment. Conclusions: Pravastatin was well tolerated over 5 years and was a very effective lipid-lowering agent for both hypercholesterolemia and hypertriglyceridemia with no effect on the biosynthesis of sex steroids. These findings suggest that pravastatin can be used in the treatment of hypercholesterolemia with/without high triglyceride levels in women around the menopause.     

丁苯酞预处理对脑缺血再灌注损伤大鼠神经功能缺损评分、氧化损伤和形态学的影响

目的探讨丁苯酞(NBP)预处理对脑缺血再灌注损伤大鼠神经功能缺损评分、氧化损伤和形态学的影响。方法 90只雄性SD大鼠随机分为假手术组(Sham)、模型组(IR)、NBP预处理低剂量组(NBPⅠ)、NBP预处理中剂量组(NBPⅡ)和NBP预处理高剂量组(NBPⅢ),每组18只,制造模型前7d开始灌胃给药,1次/d。线栓法制作大脑中动脉栓塞(MCAO)模型,缺血2h再灌注24h后进行神经功能缺损评分;2,3,-氯化三苯基四氮唑(TTC)染色观察脑组织梗死的情况;苏木素-伊红(HE)染色显微镜下观察脑组织形态学变化;采用羟胺法测定超氧化物歧化酶(SOD)活性,化学比色法测定谷胱甘肽过氧化物酶(GSH-PX)活性,硫代巴比妥酸(TBA)法测定丙二醛(MDA)含量。结果 (1)Sham组神经功能缺损评分为零,脑组织无梗死情况发生,神经元形态规则,脑组织中SOD、GSH-PX活性和MDA含量正常。(2)与IR组比较,NBP预处理各组大鼠神经功能评分显著降低(均P0.01),NBPⅠ、Ⅱ、Ⅲ组神经功能评分依次递减(均P0.05)。(3)与IR组比较,NBP预处理各组脑组织梗死体积依次减小(均P0.05),神经元损伤减轻。(4)NBP预处理各组脑组织中SOD、GSH-PX活性明显升高,MDA含量显著减少(P0.01);NBPⅠ、Ⅱ、Ⅲ组SOD、GSH-PX活性依次递增,MDA含量依次递减(均P0.05)。结论丁苯酞预处理可上调SOD、GSH-PX活性,降低MDA含量,减小脑梗死体积,减轻神经元损伤,发挥对脑缺血再灌注损伤大鼠的预防性保护作用。     

The circadian variation of cardiovascular stress levels and reactivity: Relationships to individual differences in morningness/eveningness

Two studies assessed the circadian variation of cardiovascular responses to stress in healthy and coronary artery disease (CAD) populations. In within-subjects designs, stressors were administered to healthy male subjects and male CAD patients both in the morning and afternoon, and subjects were classified as either morning or evening types using the Morningness-Eveningness Questionnaire (Horne & Östberg, 1976, International Journal of Chronobiology, 4, 97–110). No consistent circadian variation in blood pressure or heart rate responses was observed in the aggregate sample of either healthy subjects or CAD patients. However, there were significant interactions between circadian type and time of day. In both populations, morning, subjects exhibited higher cardiovascular levels during the morning session, and evening subjects exhibited higher levels during the afternoon session. Analyses of cardiovascular reactivity revealed less consistent evidence for this interaction. Self-reports of stress revealed interactions between time of day and and morningness/eveningness only in CAD sample. In CAD patients, preliminary analysis of myocardial wall function, an index of myocardial ischemia, did not reveal a significant interaction between morningness/eveningness and time of day, perhaps due to small sample size. The presence of differing circadian patterns in stress response based on individual differences in morningness/eveningness is discussed in teerms of its methodological implications for psychophysiological research and in terms of the role of stress as an acute trigger of CAD.     

Exercise training reduces oxidative stress in people living with HIV/AIDS: a pilot study

Background: Exercise training has been shown to be an effective strategy to balance oxidative stress status; however, this is underexplored in people living with HIV/AIDS (PLWHA).

Objective: To evaluate the effects of exercise training on oxidative stress in PLWHA receiving antiretroviral therapy.

Methods: Patients performed 24 sessions (3 times per week, 8 weeks) of either aerobic (AT), resistance (RT), or concurrent training (CT). Glutathione disulphide to glutathione ratio (GSSG/GSH) in circulating erythrocytes and thiobarbituric acid–reactive substances (TBARS) in plasma samples were assessed as oxidative stress markers. Eight PLWAH completed the training protocol (AT =3, RT =3, CT =2). The GSSG/GSH and TBARS values were logarithmically transformed to approximate a normal distribution. A paired t-test was used to determine the differences between baseline and post-training values.

Results: Data-pooled analysis showed a decrease in GSSG/GSH and TBARS after the training period: log GSSG/GSH= –1.26?±?0.57 versus –1.54?±?0.65, p?=?.01 and log TBARS =0.73?±?0.35 versus 0.43?±?0.21, p?=?.01. This was paralleled by a rise in peak oxygen uptake (VO_2peak?=?29.14?±?5.34 versus 32.48?±?5.75?ml kg^?1 min^?1, p?=?.04). All the subjects who performed resistance exercises showed an average gain of 37?±?8% in muscle strength with no difference between performing single or multiple sets in terms of muscle strength gain. The results reinforce the clinical importance of exercise as a rehabilitation intervention for PLWHA and emphasizes the safety of exercise at the physiological level with the potential to mediate health outcomes.     

瑞舒伐他汀抑制JNK1/2的活化对急性心力衰竭大鼠心脏血流动力学、氧化应激及免疫应答的调节

目的:探究瑞舒伐他汀(RST)抑制JNK1/2的活化对急性心力衰竭(HF)大鼠心脏血流动力学、氧化应激及免疫应答的调节机制.方法:将100只雄性SD大鼠随机选取20只作为健康对照组(Control),80只制成急性HF模型后设为模型组(Cardiac failure)、低浓度RST组(2.5 mg/kg)、中浓度RST...     

Lower serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

BACKGROUND: Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African American women. AIMS: The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49-65 years from St. Louis, Missouri. METHODS: A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 and sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and free androgen index (T/SHBG). RESULTS: Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels were independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). CONCLUSION: There is an age-related decline in serum DHEAS in African American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and depressive symptoms in this population.     

Immunological functions of oxidized human immunoglobulin G in type 1diabetes mellitus: its potential role in diabetic smokers as a biomarker of elevated oxidative stress

The role of oxidized immunoglobulin G in type 1 diabetic smokers has been investigated in the present study. Human immunoglobulin G (IgG) was modified by reactive oxygen species (ROS). The binding characteristics of circulating autoantibodies in type 1 diabetes patients against native and modified IgG were assessed by direct binding ELISA. High degree of specific binding by 68.5% of patients sera towards ROS-modified IgG was observed in comparison to its native analogue (p< 0.05). In addition, diabetic smokers (n=28) were examined and the results were compared with diabetic non-smokers (n=26). Circulating antibodies of diabetic smokers showed substantially stronger binding to modified IgG as compared with the antibodies present in diabetic non-smokers (p< 0.05). Normal human sera (n=53) showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The increase in total serum protein carbonyl levels in the diabetic smokers was largely due to an increase in oxidized IgG. Diabetic smokers showed substantially higher carbonyl contents in sera as well as in purified IgG as compared with sera and IgG of diabetic non-smokers. Collectively, the oxidation of plasma proteins, especially IgG, might enhance oxidative stress in type 1 diabetes smokers.