Sesame oil and vitamin E co-administration may improve cardiometabolic risk factors in patients with metabolic syndrome: a randomized clinical trial.

OBJECTIVES: Metabolic syndrome (MetS) represents a clustering of metabolic abnormalities that are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to evaluate the effects of sesame oil enriched with vitamin E (vit E), sesame oil alone and sunflower oil on lipid profile, fasting blood glucose (FBG), malondialdehyde (MDA), high-sensitivity C-reactive protein (Hs-CRP), homeostatic model assessment (HOMA-IR), and blood pressure (BP) in patients with MetS. SUBJECTS: Overall, 75 individuals with MetS (aged 30-70 years) participated in this randomized, single-blind controlled trial. Patients were randomly allocated to: (1) Group A (n = 25): sesame oil (30 ml/day) enriched with vit E (400 mg/day), (2) Group B (n = 25): sesame oil (30 ml/day), (3) Group C (n = 25): sunflower oil (30 ml/day). Anthropometric data, dietary intake, blood pressure, and biochemical markers, including fasting serum lipids, FBG, serum insulin, MDA, and hs-CRP were measured at baseline and at week 8. RESULTS: In individuals in the sesame oil enriched with vit E group (Group A), there were significant reductions in serum total cholesterol (TC), triglycerides (TG), FBG, HOMA-IR, MDA, hs-CRP, high-density lipoprotein (HDL-C) systolic and diastolic BP (for all the comparison p < 0.02). Similarly, in Group B (taking sesame oil alone), TC, TG, FBG, HOMA-IR, MDA, systolic and diastolic BP were significantly improved (for all the comparison p < 0.025), while there were no significant changes in serum HDL (baseline = 35.9 ± 7.2 mg/dL vs. 36.4 ± 6.2 mg/dL, p = 0.432) and hs-CRP (baseline = 4.38 ± 1.34 mg/dL vs. week 8 = 3.96 ± 1.7 mg/dL, p = 0.057) in second group. No significant changes in any of the studied clinical and anthropometric data were found in Group C (on sunflower oil). CONCLUSION: Sesame oil (±vit E) was shown to beneficially affect several cardiometabolic indices (including lipids, FBG, BP, HOMA-IR, and MDA) in patients with MetS.

The effect of electro-acupuncture on pro-oxidant antioxidant balance values in overweight and obese subjects: a randomized controlled trial study.

Objective To undertake a randomized controlled trial in 196 obese subjects to examine the effect of electro-acupuncture on serum pro-oxidant antioxidant balance (PAB) values. Methods Subjects received authentic acupuncture (cases) or sham acupuncture (controls) for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Serum PAB was measured at baseline, and 6 and 12 weeks later. Results We found that serum PAB values decreased significantly in the group receiving the authentic acupuncture compared to the sham treatment (p<0.001) at week 6, and whilst serum PAB increased significantly (p<0.05) in the second phase of the study, a significant difference between two groups remained at 12 weeks (p<0.05). Conclusions Electro-acupuncture in combination with a low-calorie diet was more effective at reducing serum PAB values in obese subjects compared to diet alone. Further work is required to determine the mechanism by which electro-acupuncture has this effect.

Enhanced detection sensitivity of prostate-specific antigen via PSA-conjugated gold nanoparticles based on localized surface plasmon resonance: GNP-coated anti-PSA/LSPR as a novel approach for the identification of prostate anomalies.

Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

The potential role of heat shock proteins in cardiovascular disease: evidence from in vitro and in vivo studies.

The heat shock proteins (HSPs) are highly conserved families of proteins expressed by a number of cell types following exposure to stressful environmental conditions. These conditions include several known risk factors for cardiovascular disease. A number of the HSPs have been shown to be molecular chaperones that are involved in the refolding of other damaged protein molecules. Over the past two decades there has been an increasing interest in the relationship between HSPs and cardiovascular disease, and particularly whether an autoimmune response may be implicated. The fact that microorganisms also produce HSPs, and that these are homologous to human HSPs has given rise to concept of molecular mimicry. While most of the past studies have focused on HSP 65 and 70, there has been recent interest and investigations of the possible role of the smaller HSPs, such as HSP27, in atherogenesis. Furthermore, the possibility that autoimmunity may be mediating the deleterious effects of HSPs has led some investigators to explore tolerization as a potential therapeutic approach.

The relationship between established coronary risk factors and serum copper and zinc concentrations in a large Persian cohort.

INTRODUCTION: The relationship between demographic and biochemical characteristics, including several established coronary risk factors, and serum copper and zinc was assessed in a large Iranian population sample. MATERIALS AND METHODS: A group of 2233 individuals, 15-65 years of age [1106 (49.5%) males and 1127 (50.5%) females] was recruited from residents of the Greater Khorasan province in northeast of Iran. Demographic data were collected using questionnaires. Coronary risk factors were determined using standard protocols, and trace elements were measured in serum using atomic absorption spectroscopy. RESULTS: Degree of glucose tolerance and smoking habit were not associated with serum zinc and copper levels. Serum copper levels were significantly higher in obese and hypertensive than in normal subjects (p<0.001). In the whole group and for the female subgroup, serum zinc (p<0.01) and copper (p<0.001) were both significantly lower in individuals with normal versus high levels of low-density lipoprotein cholesterol. A strong positive correlation was found between serum copper and body mass index (BMI) (r=0.85, p<0.001). Weaker positive associations were found between serum copper and calculated 10 years' coronary risk (r=0.11, p<0.001). Serum zinc/copper ratio was strongly inversely associated with calculated 10 years' coronary risk (r=-0.10, p<0.001). The partial Eta squared (PES) values for factors determining serum zinc were hypertension (0.007, p=0.01) and BMI (0.004, p=0.01); and for serum copper, they were gender (0.02, p=0.001), hypertension (0.004, p=0.009), and 10 years' coronary risk for men (0.003, p=0.03) and women (0.002, p=0.07). CONCLUSION: Significant associations between serum trace element concentrations and several coronary risk factors, including calculated 10 years' coronary risk scores, were found.

Aluminium administration is associated with enhanced hepatic oxidant stress that may be offset by dietary vitamin E in the rat.

It has been proposed that aluminium toxicity may be mediated, at least in part, by free radical generation. We have investigated the effects of aluminium lactate administration on indices of hepatic oxidant stress, and the consequences of concomitant dietary vitamin E, in male albino Wistar rats. Aluminium lactate was administered for 4 weeks, by ip injection at 10 mg aluminium/kg body weight. Groups of animals received a chow diet containing 0, 5, 15, or 20 mg vitamin E/g of food. A control group of rats received a normal chow diet, without being injected with aluminium. The rats were killed after 4 weeks, and blood and liver tissue removed for the measurement of aluminium and markers of oxidative stress. Plasma and liver aluminium levels were increased in all groups of animals receiving aluminium lactate (P < 0.01), although these levels were significantly reduced in rats receiving concomitant vitamin E (P < 0.05). Aluminium treatment was associated with significantly increased levels of hepatic reactive oxygen species (ROS) (P < 0.01) that were attenuated by concomitant vitamin E (P < 0.05). Hepatic catalase and reduced glutathione levels were both reduced in animals treated with aluminium (P < 0.05).

Genetic markers to predict polygenic disease: a new problem for social genetics.

Many genetic markers that relate to common multifactorial disease in adults have been identified during the past 15 years. Their use as adjuncts for the diagnosis, prognosis, prediction of disease or targeting therapy for these disorders has begun, good examples being the Factor V Leiden mutation for venous-thromboembolism, lipoprotein lipase mutations for hypertriglyceridaemia and the apolipoprotein E4 variant for Alzheimer's dementia. However, extensive gene-gene and gene-environment interactions make their use more complex than markers for the simpler monogenic disorders (such as cystic fibrosis, or Duchenne's muscular dystrophy). Possible misapplication of the genetic markers for multifactorial disease in the fields of risk prediction, direct sales to the public, life assurance, employment rights, and legislation for regulation of their use are discussed.

Endogenously elicited antibodies to platelet derived growth factor-BB and platelet cytosolic protein inhibit aortic lesion development in the cholesterol-fed rabbit.

Several studies have indicated that growth factors, such as platelet derived growth factor (PDGF), may be important in atherogenesis. These factors are released from platelets, or expressed by cells of the arterial wall. In order to study their role in atherogenesis more directly, rabbits were immunized with PDGF-BB, platelet cytosolic protein, or human serum albumin (HSA), until high titres of antibody were attained. Atherosclerotic lesions were subsequently induced by feeding the animals with a 2% cholesterol enriched diet. At the end of approximately 3 months, the extent of aortic lesion development was assessed by image analysis of en face preparations of aortae stained with Oil Red-O, and histological segments of aortae taken at the level of the first intercostal artery branch point. The endogenous antibodies were characterized with respect to their cross-reactivity, and ability to neutralize PDGF and platelet cytosol-induced cell proliferation and migration in vitro. The endogenous, anti-PDGF-BB antibody was isoform specific, and neutralized the mitogenic and chemotactic properties of PDGF-BB and rabbit platelet cytosolic protein in vitro. The anti-platelet cytosol antibody partially inhibited the chemotactic and mitogenic properties of rabbit platelet cytosolic protein. Compared to non-immune rabbits (n = 5), animals immunized with HSA (n = 4) had a significantly larger area of aortic lesion involvement (P < 0.01), whereas aortic lesions in rabbits immunized with PDGF-BB (n = 5), or platelet cytosolic protein (n = 7) were significantly smaller than either non-immune animals, or animals immunized with HSA (P < 0.05). The same pattern was observed for other measures of aortic lesion involvement including aortic intima:media ratio at the level of the first intercostal artery. These data suggest that PDGF-BB, and possibly other platelet-associated growth factors, are involved in cholesterol-induced atherosclerosis.

RT-PCR study on the effects of minimally modified low-density lipoproteins and probucol treatment on gene expressions of interleukin-1 and platelet-derived growth factor B-chain in human peripheral blood mononuclear cells.

Oxidatively modified low-density lipoprotein has been identified in early atherosclerotic lesions and may play an important role in atherogenesis. Minimally modified low-density lipoprotein (MM-LDL) derived by prolonged storage under sterile conditions results in mild oxidation and is recognised by the LDL receptor rather than the scavenger receptor. Therefore, it may be closer to the real pathophysiological circumstances in the initial state of atherosclerosis. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique, the present study demonstrates that MM-LDL is capable of inducing gene expression of both interleukin-1 alpha (IL-1 alpha) and interleuking-1 beta (IL-1 beta) in human peripheral blood mononuclear cells in a dose-dependent manner. Concomitant treatment of the cells with the anti-oxidant probucol results in an inhibitory effect in steady-state levels of both IL-1 alpha and IL-1 beta mRNA and the effects were also shown in a dose-dependent fashion. We also found an inhibitory effect of MM-LDL on gene expression of platelet-derived growth factor B chain (PDGF-B) mRNA levels by mononuclear cells. Hence MM-LDL is biologically active and may contribute to the early stages of atherogenesis by stimulating the inflammatory cytokine IL-1 and the efficacy of probucol in inhibiting the progression of atherosclerosis may be due, both to its inhibition of IL-1 expression by intimal macrophages, and its prevention of LDL oxidation.

Insulin-like growth factor-I modulates monocyte adhesion to EAhy 926 endothelial cells.

IGF-I is a ubiquitous growth factor, found in platelets and elaborated by many other cell types. It is thought to be involved in several pathophysiological processes including embryonic development, angiogenesis and wound healing. We report that the adherence of human peripheral blood monocytes to an endothelial cell line (EAhy 926) is inhibited in a dose and time-dependent manner by pre-incubating the endothelial cells with IGF-I (P < 0.001). Monocyte adhesion was inhibited 17.9 +/- 1.9% by IGF-I at a dose of 1000 ng/ml (P < 0.01). In contrast, IGF-I had no significant effect on monocyte adherence to plastic. The inhibitory effects of IGF-I were reversed by co-incubating the endothelial cells with the nitric oxide synthase inhibitor, L-NAME. These data suggest that the effects of IGF-I are mediated by the release of nitric oxide from the endothelial cells.

Recombinant insulin-like growth factor-1 modulates aggregation in human platelets via extracellular calcium.

Insulin like growth factor-1 (IGF-1) potentiated aggregation of human platelets induced by thrombin-, collagen- and ADP in a dose-dependent manner over the range 30-300 nM. IGF-1 (100 nM) reduced EC50 values for thrombin, collagen and ADP-induced aggregation by 19.6%, 53.6% and 22.8% respectively. Potentiation by IGF-1 was dependent on the presence of extracellular Ca2+ and was inhibited by verapamil or nifedipine. Further, IGF-1 enhanced the elevation in free intraplatelet Ca2+ induced by the platelet agonists collagen and thrombin.

Hyaluronan (HYAL-BV 5200) inhibits neo-intimal macrophage influx after balloon-catheter induced injury in the cholesterol-fed rabbit.

Hyaluronan is a glycosaminoglycan, elaborated by several cell types, and is a major constituent of the extracellular matrix. Recent studies suggest that hyaluronan influences cell migration and proliferation. At high concentrations, it has been shown to inhibit macrophage migration in vitro. We have investigated the effects of hyaluronan administration on neo-intimal lesion development following balloon catheter injury of the common carotid artery in the cholesterol-fed New Zealand White rabbit. Hyaluronan, administered as sodium hyaluronate at the time of surgery and daily until sacrifice, 2 weeks later, reduced the absolute neo-intimal response to injury by 42% (117 +/- 16 microns to 68 +/- 11 microns; P < 0.05), and the intima-media ratio by 35% (0.91 +/- 0.10 to 0.59 +/- 0.11; P < 0.05). This was associated with a 62% reduction in intimal macrophage content (8.63 +/- 1.85% to 3.25 +/- 1.05%; P < 0.02). At the time of killing, serum cholesterol levels and weight gain were comparable between the groups of animals receiving a cholesterol diet (P > 0.05). In both groups mean serum cholesterol levels at the time of the balloon injury and killing were significantly greater than at entry (P < 0.001), and significantly higher than in a group receiving control chow (P < 0.001). These data suggest that the effect of hyaluronic acid on neo-intimal size may be mediated, in part, by an inhibition of monocyte/macrophage influx, and support the view that hyaluronan impairs monocyte migration.

Vitamin E inhibits the intimal response to balloon catheter injury in the carotid artery of the cholesterol-fed rat.

We have investigated the effect of the naturally occurring, lipid-soluble antioxidant, vitamin E, on the intimal response to balloon injury in the cholesterol-fed rat. We found that in animals receiving a 0.5% vitamin E plus 1% cholesterol diet, neo-intimal thickening was reduced by 30% (P < 0.025) compared to animals receiving either cholesterol alone, or a control chow diet. In all three dietary groups, the intimal lesion consisted predominantly of smooth muscle cells, and few monocytes/macrophages (< 0.5%) could be identified by staining with the monoclonal antibody ED-1. In vitro, vitamin E inhibited platelet-derived growth factor- (PDGF) (20 ng/ml) and serum (2%)-induced mitogenesis of both adult rat thoracic aortic smooth muscle cells and an embryonic rat aortic smooth muscle cell line (A7r5), dose-dependently. These data suggest that reactive oxygen species may be involved in the intimal response to balloon catheter injury, and that antioxidants, such as vitamin E, may offer some protection against restenosis. Although the way by which it does so is unclear, one possible mechanism is by a direct inhibitory effect on the accumulation of smooth muscle cells within the developing neo-intima.

Probucol inhibits neointimal thickening and macrophage accumulation after balloon injury in the cholesterol-fed rabbit.

Restenosis is a frequent long-term complication after balloon angioplasty. Although smooth muscle cells form the major constituent of the occluding lesion, macrophage-derived foam cells are usually also present in high abundance. The latter have the potential to accelerate the rate of reocclusion because they elaborate many potent cytokines and growth factors, which may act to either recruit cells into the neointima or cause neointimal cell proliferation. Macrophage-derived foam-cell formation depends upon the uptake of modified low density lipoprotein via a scavenger receptor-mediated pathway. Foam-cell formation is accompanied by the release of smooth muscle cell mitogens and chemoattractants. We have examined the effects of probucol, a lipid-soluble antioxidant, in the balloon-catheterized carotid artery of the cholesterol-fed rabbit to evaluate the importance of oxidative processes in restenosis. After 5 weeks, serum cholesterol levels were 32% lower (P < 0.05) in rabbits fed 1% probucol with 2% cholesterol, compared with those receiving cholesterol alone. Probucol inhibited neointimal macrophage accumulation by 68% (P < 0.001), reduced absolute intimal size by 51% (P < 0.05), and reduced the intima/media thickness ratio by 51%. These inhibitory effects were directly related to serum probucol concentrations and appeared to be unrelated to probucol's hypocholesterolemic activity. These data suggest that reactive oxygen species may be involved in the intimal response to injury and that antioxidants, such as probucol, may be therapeutically useful as inhibitors of restenosis.

Arterial response to mechanical injury: balloon catheter de-endothelialization.

Coronary angioplasty has been used clinically for over a decade. Its initial promise as an alternative to coronary bypass surgery has only partially been fulfilled because of the high rate of post-operative restenosis. A number of animal models have been devised to study this phenomenon and although none is entirely satisfactory, they have, together with recent advances in molecular biology provided an insight into the cellular mechanisms that may contribute to this complication. This knowledge may ultimately lead to a means of therapeutic intervention. This review summarises our present understanding of the pathology of post-angioplasty re-stenosis as revealed by studies using the balloon catheter de-endothelialization model, and discusses some of the intervention strategies that have been attempted.

Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF.

Approximately 30 to 40 percent of atherosclerotic coronary arteries treated by angioplasty or by bypass surgery occlude as a result of restenosis. This restenosis is due principally to the accumulation of neointimal smooth muscle cells, which is also a prominent feature of the advanced lesions of atherosclerosis. The factors responsible for the accumulation of intimal smooth muscle cells have not been identified. Platelet-derived growth factor (PDGF) is a potent smooth muscle chemoattractant and mitogen. It is present in platelets and can be formed by endothelium, smooth muscle, and monocyte-derived macrophages. The development of an intimal lesion in the carotid artery of athymic nude rats induced by intraarterial balloon catheter deendothelialization was inhibited by a polyclonal antibody to PDGF. These data demonstrate that endogenous PDGF is involved in the accumulation of neointimal smooth muscle cells associated with balloon injury and may be involved in restenosis after angioplasty, and perhaps in atherogenesis as well.

The insulin-like growth factors: their putative role in atherogenesis.

Smooth muscle cell proliferation and leukocyte infiltration are characteristic features of all lesions of atherosclerosis. Although platelet derived growth factor (PDGF) is one of the major smooth muscle mitogens, other important mitogenic factors are found in plasma and in platelets. The insulin-like growth factors (IGF-I and IGF-II) are present in plasma complexed to one of a number of IGF-binding proteins (IGF-BP). They are also found at high concentrations within the alpha-granules of platelets. The IGFs are secreted by a number of cell types in-vitro and in-vivo, including smooth muscle cells and macrophages. The cellular effects of the IGFs are mediated by membrane bound high affinity receptors. IGF receptors are of two distinct types and are expressed by a wide variety of cells. The IGFs are potent smooth muscle cell mitogens and it is therefore possible that these polypeptides contribute to the formation of the atherosclerotic lesion by paracrine, autocrine or endocrine mechanisms.

High density lipoprotein subfractions and coronary risk factors in normal men.

Plasma levels of total high density lipoprotein cholesterol (HDL) and its subfractions (HDL2 and HDL3) were measured in 366 healthy Caucasian males; these values were related to a number of coronary risk factors. On univariate statistical analysis, total HDL was negatively correlated with cigarette consumption, body mass index, and serum triglycerides, and positively associated with level of physical activity and alcohol consumption. HDL2 showed an inverse relationship with cigarette consumption, body mass index, triglycerides, and systolic blood pressure and a positive relationship with age. HDL3 was negatively correlated with cigarette smoking, body mass index, and triglycerides and positively associated with exercise level and alcohol consumption. Total HDL and HDL2 were inversely related to coronary risk rating, but HDL3 showed no significant correlation. Many of these relationships became nonsignificant after allowing for the effects of other variables. In particular, none of the HDL measurements correlated significantly with risk score after allowing for the effect of triglycerides. There is insufficient evidence at present to recommend the inclusion of HDL subfractions as routine screening tests for heart disease.