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1.
High plasma concentration of low-density lipoprotein (LDL) is associated with increased risk of atherosclerosis. Modified forms of LDL, especially oxidized LDL play a major role in its pathogenesis. This article gives detailed insight into the kinetics ofin vitro LDL oxidation by copper at different concentrations in normal and high-risk group subjects. Basal level of oxidatively modified LDL was significantly higher in ischaemic heart disease (IHD) and IHD hyperlipidemic subjects compared to normolipidemic and, hyperlipidemic control subjects, respectively. Derivatization of amino groups of apo-lipoprotein as monitored by estimating free amino groups concentration, was significantly higher in high-risk group and established IHD cases. Kinetics of oxidation was studied with two different concentrations of CuSO4 (2.5 mM and 7.5 mM). thiobarbituric acid reactive substances (TBARS) level increases with time, and up to 95% oxidation was observed in 8 hr. About 60–65% less free amino groups were observed in native-LDL isolated from IHD patients compared to normal subjects. Study also showed an increase in two oxidative products studied, 20α-OH-cholesterol and 4-cholesten-3-one with oxidation time accompanied by corresponding decrease in LDL cholesterol. Increase in oxidative species was more evident in high-risk group and IHD patient. Basal level of oxidatively modified LDL measured in terms of TBARS was significantly higher in present study, strongly support that the extent of LDL oxidation monitored as TBARS and FAG level in circulating-LDL could be used as risk marker for high risk group.  相似文献   

2.
Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-activated platelets adhered to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. To measure platelet adhesion and aggregation, the migration distance (MD) of blood through the microchannel was monitored. As the microstirrer speed increased, MD initially decreased exponentially but then increased beyond a critical rpm. For platelet-excluded blood samples, there were no changes in MD with increasing stirrer speed. These findings imply that the stirrer provided sufficiently high shear to activate platelets and that blood MD is a potentially valuable index for measuring the shear-dependence of platelet activation. Our microfluidic system is quick and simple, while providing a precise assay to measure the effects of shear on platelet aggregation and adhesion.  相似文献   

3.
The normal coagulation process is initiated by disruption and exposure of the subendothelial components of blood vessels. Platelets adhere to subendothelium-bound von Willebrand factor via glycoprotein (GP) Ib complex. This initial interaction per se and the release of platelet agonists transduce signals that leads to the rise in intracellular Ca2+ which induces shape change, prostaglandin synthesis, release of granular contents and conformational changes in platelet Gp IIb-IIIa. Gp IIb-IIIa in activated platelets binds fibrinogen and other adhesive proteins and mediates platelet cohesion the primary haemostatic plug. Furthermore, the activated platelets due to aggregation, result in the formation of fibrin (secondary hemostasis). Normally the haemostatic process plays a delicate balance between keeping the blood in the fluid state to maintain flow and rapidly forming an occluding plug following vessel injury. Thrombosis occurs because of alteration in this delicate balance. Arterial thrombosis occurs in the setting of previous vessel wall injury mostly because of atherosclerosis, while venous thrombosis occurs in areas of stasis. The recent advances in understanding of the haemostatic process have led to a better understanding of the mechanism of action of many antithrombotic drugs and identification of new targets for drug development. The molecular target of the ticlopidine has been identified. Large numbers of IIb-IIIa inhibitors have been developed. The mechanism of action of heparin has been defined at the molecular level. As a result, a synthetic pentasaccharide, based on antithrombin-binding domain of heparin, has been developed and tested successfully in clinical trials. New generation direct thrombin inhibitors are being developed. Factor Xa has a critical position at the convergence of intrinsic and extrinsic pathway. The clinical tolerability and the efficacy of low molecular weight heparins has established that inhibition of further thrombin generation, by blocking factor Xa alone can be an effective way of preventing thrombus growth without inactivating thrombin. A large number of specific factor Xa inhibitors are under development. Some of these are in preliminary clinical trials and appear to be promising. Future clinical trials will determine whether these new drugs will provide better risk-benefit ratio in treatment of thrombotic disorders. Similarly role of thrombolytics has been clearly established in many diseases including coronary artery disease.  相似文献   

4.
Vascular thrombotic disorders have emerged as a serious threat to our society. Platelet adhesion to fibrinogen, collagen and other platelet activators exposed over the atherosclerotic plaques can trigger platelet signaling events, activate platelets and lead to thrombotic events. Since anticoagulant and thrombolytic treatment strategies are usually associated with serious bleeding complications, preventing platelets adhesion may help to maintain platelets in an inactive state. In this study we tried to find out the effect of Silver nanoparticles, through their interaction with various platelet surface integrins on platelet adhesion on immobilized fibrinogen. Platelets, isolated from anti-coagulated human whole blood sample from healthy donors, were suspended in physiological buffer and each sample was divided into four tubes. In three of them 0.05, 0.5, and 5 μM concentrations of Silver nanoparticles were added, fourth tube served as control. Platelet adhesion on immobilized fibrinogen matrices and integrin mediated cell signaling events were studied in all the four samples. In the present study we show that nanosilver prevent platelet adhesion without conferring any lytic effect on them and effectively prevents integrin-mediated platelet responses in a concentration-dependent manner.  相似文献   

5.
Total lipids, cholesterol, phospholipids, free fatty acids, total glycerides and lipoprotein lipase (LPL) activity of 26 patients of Ischaemic Heart Disease (IHD) and similar number of age and sex matched control individuals were studied to find out abnormality in lipid metabolism. Incidence of IHD was more common amongst males as compared to females. Significant low levels of serum LPL activity and higher levels of other parameters was thus evident in patients of IHD and this may explain the altered lipid metabolism and hypertriglyceridemia in patients of IHD.  相似文献   

6.
The oxidative modification of lipoprotein especially low density lipoprotein (LDL) plays a key role in the initiation and progression of atherosclerosis. Serum apolipoproteinB (apoB) level is found to be an important marker for atherosclerosis. The present paper focuses on the measurement of serum apoB levels and the effect of Vitamin E, Vitamin C and reduced glutathione on the copper ion induced oxidation of LDL + VLDL (VLDL-Very Low Density Lipoprotein) lipoprotein fraction isolated from the serum of chronic renal failure (CRF) and renal transplanted patients. The level of apoB is significantly higher in the serum of transplanted patients when compared to CRF patients and normal subjects. The level of TBARS formed in oxidized LDL + VLDL lipoprotein fraction of CRF and renal transplanted patients are significantly increased than normal even in the presence of antioxidants but the level of TBARS produced, with antioxidants is comparatively lesser than that produced by oxidized lipoprotein fraction without antioxidants. It may be concluded than that produced by oxidized lipoprotein fraction without antioxidants. It may be concluded that oxidation of LDL can be prevented at an earlier stage by Vitamin E supplementation. The supplementation with Glutathione serves as the best method of preventing the lipoprotein oxidation among the renal diseased patients.  相似文献   

7.
Lipid peroxidation (MDA) was studied spectrophotometrically in relation to lipidemic status and atherogenic index in IHD and IHD risk subjects. It was found to be significantly elevated compared to control subjects (P<0.005) in both the groups, showing a linear correlation with cholesterolemic status. The values were found to run parallel to atherogenic index. In 10% cases with borderline atherogenic index the lipid peroxidation was found to be highly elevated. It is speculated that it may have a future role as a marker for IHD risk specially in premature group.  相似文献   

8.
老年人血小板谷胱甘肽过氧化物酶的纯化和分子特性研究   总被引：1，自引：0，他引：1  
陈伟平 Rey  C 《科技通报》1994,10(4):247-250
报道老年人血小板谷胱甘肽过氧化物酶由ＳｅｐｈａｒｏｓｅＱ柱层析、ＭｏｎｏＱＨＲ５／５ＦＰＬＣ和亲和层析后，经ＳＤＳ／ＰＡＧＥ鉴定为一条区带，其分子量为２３ｋＤａ．等电聚焦测定ＰＩ为５．１．用Ｓｕｐｅｒ－ｏｓｅＨＲ１０／３０柱经ＦＰＬＣ测定的分子量为９２ｋＤａ，这表明在自然状态下血小板谷胱甘肽过氧化物酶由四个相同的亚单位组成。这些结果与人红细胞谷胱甘肽过氧化物酶的特性相一致．  相似文献   

9.
With a view to gain an insight into the regulation of calcium activated neutral protease by its endogenous inhibitor, the inhibitor was quantitated in platelets and lymphocytes of Duchenne muscular dystrophy patients and controls by dot immunoblot procedure using polyclonal antibodies against the inhibitor. A two fold increase in inhibitor levels was observed in lymphocytes but no significant increase in inhibitor levels in platelets from Duchenne muscular dystrophy. These results suggest that different regulatory mechanisms of modulation of CANP operate in these two cell types in Duchenne muscular dystrophy.  相似文献   

10.
Traditionally Friedewald formula has been used to calculate low density lipoprotein cholesterol (LDL-C) concentration though now direct homogenous methods for its measurement are also available. Clinical guidelines recommend the use of calculated LDL-C to guide therapy because the evidence base for cholesterol management is derived almost exclusively from trials that use calculated LDL, with direct measurement of LDL-C being reserved for those patients who are non fasting or with significant hypertriglyceridemia. In this study our aim was to compare calculated and direct LDL and their variation at different cholesterol and triglyceride levels. Fasting lipid profile estimation was done on 503 outpatients in a tertiary hospital. Both direct and calculated LDL were then compared. Mean fasting direct LDL was found to be higher than calculated LDL in 87.1 % of subjects by 8.64 ± 8.35 mg/dl. This difference was seen a all levels of cholesterol and triglyceride. Using 130 mg/dl LDL cholesterol as cut off fewer subjects were classified as high risk by calculated LDL than direct LDL. In conclusion, direct LDL is higher than calculated LDL. Compared with direct measurement, the Friedewald calculation underestimates the risk for ischemic heart disease.  相似文献   

11.
Patients with type II Diabetes Mellitus (NIDDM) are more prone to Ischaemic Heart Disease (IHD). Although, oxygen free radicals are known to contribute to the development of IHD, conflicting reports are available regarding the antioxidant status in patients of NIDDM complicated with IHD. This study was undertaken to investigate the oxidative status in patients of NIDDM and to assess their correlation with plasma glucose, glycosylated haemoglobin and duration of diabetes. The levels of malondialdehyde were significantly increased where as levels of superoxide dismutase, Glutathione peroxidase and vitamin C were significantly decreased in diabetics without complications and non-diabetics with IHD when compared with the controls. The levels of malondialdehyde and Glutathione peroxidase were significantly increased where as levels of superoxide dismutase and vitamin C were significantly decreased in diabetics with IHD when compared with diabetics without complications and non-diabetics with IHD. The implications of the results are discussed.  相似文献   

12.
薛莉  单江  陈乃云  胡忠荣 《科技通报》2004,20(6):552-555,559
目的研究氧化型低密度脂蛋白(oxidized LDL, ox-LDL)是否能在基因和蛋白两个水平诱导内皮细胞表达凝集素样氧化低密度脂蛋白受体(lectin-like oxidized LDL receptor, LOX-1),以探讨LOX-1在动脉粥样硬化形成和发展中的作用.方法将不同浓度ox-LDL(20,40,60,80 mg/L)与内皮细胞共孵育24 h及浓度40 mg/L的ox-LDL作用内皮细胞不同时间(0、3、6、12、24 h),反转录聚合酶链反应检测LOX-1 mRNA水平表达,细胞酶联免疫法测定LOX-1蛋白水平表达.结果加入Ox-LDL 20 mg/L使LOX-1 mRNA和蛋白表达量增加(P＜0.01),40 mg/L使其表达量达最高峰,随后逐渐下降.而同一浓度下从0 h～24 h的趋势是LOX-1 mRNA和蛋白逐渐增加(P＜0.01),在12 h增加最明显.结论氧化型低密度脂蛋白呈剂量依赖性和时间依赖性地上调LOX-1 mRNA和蛋白表达,LOX-1可能在动脉粥样硬化形成和发展中起重要作用.  相似文献   

13.
Modification of platelet proteins by free radicals and glycation has been studied in the present work, as anin vitro model. The results of the two parameters, SDS-PAGE and carbonylation study are quite corroborative. We observed that the inducers like ferrous sulphate, ascorbate (mainly in supraphysiological concentration) and glucose attack the protein in a dose dependent manner, of which ferrous sulphate is most potent. Proteins from aged and degenerative conditions like malignancy and diabetes mellitus have suffered greater damage than normal adult and foetal proteins. The individual life expectancy in terms of biological versus chronological age may also be worked out from the individual stress level.  相似文献   

14.
Four groups of subjects: normal healthy normotensive nonpregnant women (Group A), normal normotensive pregnant women (Group B), women with preeclamptic toxaemia (Group C) and eclamptic women (Group D): with fifty subjects in each group, were investigated for serum lipid profile in the third trimester of pregnancy. There was significant increase in serum triglyceride and VLDL cholesterol leve as well as decrease in LDL cholesterol in normal pregnancy, while total cholesterol and HDL cholesterol levels did not show any statistically significant alteration. The preeclampsia (Group C) was associated with a significant rise in triglyceride and VLDL cholesterol and fall in HDL cholesterol concentration, while eclamptic women showed significant fall in HDL cholesterol and rise in LDL cholesterol as compared to normal pregnant women. However, interestingly, elevation of the ratios of total cholesterol: HDL cholesterol and triglyceride: HDL cholesterol as well as diminuition of the ratio of HDL cholesterol: VLDL cholesterol showed statistical significance in pregnancy induced hypertension in both Groups C and D, while eclamptic women showed significant elevation of LDL cholesterol: HDL cholesterol ratio in addition.  相似文献   

15.
Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18–25 and 40–60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.  相似文献   

16.
Platelets play important role in precipitating ischaemic myocardial syndromes in many ways. One of the consequences of ischaemic diseases is excessive generation of oxygen derived free radicals that have numerous pathophysiological consequences. Platelet pro-oxidant enzyme, xanthine oxidase is one of the sources of generation of free radicals. In the present paper, we report the effect of administration of vitamin E along with aspirin on the levels of platelet xanthine oxidase and extent of free radical mediated damage in the patients reperfused after myocardial infarction. Our findings show that administration of 400 mg. vitamin E for six days along with 80 mg. aspirin has an excellent anti-oxidant effect as evidenced by reduced platelet xanthine oxidase activity and lowering of malondialdehdye (MDA) levels which is an index of the extent of free radical mediated damage.  相似文献   

17.
Pathogens, especially Gram-negative bacteria or bacterial endotoxin, along with other classical factors, may be involved in inflammatory response within the aortic endothelium during the progression of cardiovascular disease. Studies have shown that bacterial endotoxin activates various inflammatory processes in the body. Our study aims to establish a correlation between endotoxemia and vascular expression of antioxidant enzymes. Swiss albino mice (4 weeks old) were fed a high fat diet for 24 weeks and then were administered Escherichia coli endotoxin intraperitonealy, for 4 weeks. Tissue antioxidant enzymes, serum levels of IL-6 and TNF alpha were measured from the mice. We report that i.p. administration of endotoxin to hyperlipidemic mice resulted in elevation of superoxide dismutase and catalase enzymes, which was paralleled by a systemic reduction of serum cholesterol and LDL expression. Myeloperoxidase levels were also found to be elevated in aortic tissue, while an increase was also observed in the serum cytokine levels.  相似文献   

18.

Background

Platelet satellitism is a phenomenon of unknown etiology of aggregating platelets around polymorphonuclear neutrophils and other blood cells which causes pseudothrombocytopenia, visible by microscopic examination of blood smears. It has been observed so far in about a hundred cases in the world.

Case subject and methods

Our case involves a 73-year-old female patient with a urinary infection. Biochemical serum analysis (CRP, glucose, AST, ALT, ALP, GGT, bilirubin, sodium, potassium, chloride, urea, creatinine) and blood cell count were performed with standard methods on autoanalyzers. Serum protein fractions were examined by electrophoresis and urinalysis with standard methods on autoanalyzer together with microscopic examination of urine sediment. Erythrocyte sedimentation rate, blood culture and urine culture tests were performed with standard methods.

Results

Due to typical pathological values for bacterial urinary infection, the patient was admitted to the hospital. Blood smear examination revealed phenomenon, which has persisted for three weeks after the disease has been cured. Blood smears with EDTA as an anticoagulant had platelet satellitism whereas the phenomenon was not observed in tubes with different anticoagulants (Na, Li-heparin) and capillary blood.

Discussion

We hypothesize that satellitism was induced by some immunological mechanism through formation of antibodies which have mediated platelets binding to neutrophil membranes and vice versa. Unfortunately we were unable to determine the putative trigger for this phenomenon. To our knowledge this is the second case of platelet satellitism ever described in Croatia.Key words: blood platelets, thrombocytopenia, EDTA, urinary infection  相似文献   

19.
Rats fed with hypercholesterolemic diet showed a significant increase in serum total—cholesterol, liver homogenate total-cholesterol, HDL-cholesterol and changed LDL-cholesterol, and HDL/LDL ratio in comparison to control. Flaxseedchutney (FC) supplemented diet (15%, w/w) was found to be more effective in restoring lipid profile changes in rats fed with cholesterol, (1.0%). The activities of serum marker enzymes glutamate oxaloacetate transminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were elevated significantly in carbon tetrachloride induced rats. Administration of flaxseedchutney (15%, w/w) resulted in depletion of serum marker enzymes and exhibited recoupment thus showing significant hepatoprotective effect. It was observed that flaxseedchutney supplemented diet could lower the serum cholesterol and as a potential source of antioxidants it could exert protection against hepatotoxic damage induced by carbon tetrachloride (CCl4) in rats.  相似文献   

20.
Low density lipoprotein (LDL) was isolated from normal rabbits and was modified with acetic anhydride. Blood monocyte derived macrophages from normal and hypercholesterolemic (HC) rabbits were cultured, and on the 8th day the cells were incubated with native and modified LDL to study their binding and degradation. Macrophages from both normal and hypercholesterolemic rabbits express a limited number of receptors for normal plasma LDL whereas they exhibit a large number of receptors for acetyl LDL. There was no significant difference between binding and degradation of acetyl LDL by normal or hypercholesterolemic cells. However, binding and degradation of native LDL by monocytes of hypercholesterolemic cells were significantly less (p<0.0001) in comparison to binding and degradation of native LDL by normal cells indicating that there is a feedback inhibitory pathway in the cell that inhibits the synthesis of LDL receptors in the presence of excess LDL.  相似文献   

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