Association of dietary patterns and risk of cardiovascular disease events in the MASHAD cohort study.

BACKGROUND: Cardiovascular disease (CVD) is the principal cause of mortality and disability in Iranian adults. We aimed to evaluate the relationship between dietary patterns and CVD incidence in a large sample of adults in northeastern Iran. METHODS: The present study comprised a prospective study of 5706 CVD-free men and women aged 35-65 years who participated in a cohort study. All of the participants were followed up for a 6-year period. Dietary patterns were derived from a 65-item validated food frequency questionnaire and the factor analysis method was used to determine dietary patterns. RESULTS: We identified two major dietary patterns: (i) a Balanced dietary pattern (a high intake of green leafy vegetables, other vegetables, fruits, dairy products, red meats, poultry, seafoods, legumes and nuts, as well as a low intake of sugar) and (ii) a Western dietary pattern (a high intake of sugar, tea, egg, snacks, fast foods, potato, carbonated beverages, pickled foods, organs meat and butter) by factor analysis. The hazard ratio (HR) and 95% confidence intervals (CIs) of total CVD in the highest versus lowest tertiles of the Balanced pattern were 1.29 (95% CI = 0.67-2.47; P = 0.44). The HR and 95% CIs of CVD in the highest versus lowest tertiles of Western pattern were 2.21 (95% CI = 1.08-4.45; P = 0.03). CONCLUSIONS: During the 6-year follow-up, we found that adherence to a Balanced dietary pattern was not significantly associated with CVD events. However, adherence to a Western dietary pattern was associated with a significantly increased risk of CVD events and its associated risk.

Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex, incompletely understood, etiology. Several genetic and environmental factors are suspected to be involved in its aetiology. Oxidative stress may be implicated in the pathogenesis of SLE and may be affected by trace element status. Zinc (Zn), copper (Cu) and selenium (Se) are essential components of several anti-oxidative enzymes and are also involved in several immune functions. The current study aimed to assess the relationship between serum concentrations of these trace elements and the clinical disease activity of SLE assessed using the SLE disease activity index (SLEDAI). Serum concentrations of albumin (Alb) (p = 0.001), Se (p = 0.001), Zn (p = 0.001) and the Zn to Cu ratio (Zn/Cu R) (p = 0.001) were lower in patients with SLE than the age- and sex-matched healthy controls. However, only Alb (p = 0.001) and Cu (p = 0.03) were negatively correlated with disease activity, which was supported by regression analysis. In summary, lower serum values of Alb, Zn, Se and Zn/Cu R were found in SLE patients compared with healthy controls; however, in addition to serum Alb concentrations, serum Cu concentrations were also negatively correlated with lupus disease activity.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Selenium supplementation and premature (pre-labour) rupture of membranes: a randomised double-blind placebo-controlled trial.

The aim was to determine if selenium supplementation during pregnancy reduces the occurrence of premature (pre-labour) rupture of membranes (PROM). A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomised to receive 100 microg of selenium (n = 83, drop-outs = 22) or a placebo (n = 83, drop-outs = 19) per day until delivery. The incidence of PROM, as well as serum selenium concentrations were evaluated at baseline and at the end of the study. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration at term (p < 0.001). In contrast, mean serum selenium concentration remained unchanged in the control group (p > 0.05). The incidence of PROM was significantly lower in the selenium group (n = 8, 13.1%) than in the control group (n = 22, 34.4%) (p < 0.01). Our findings indicate that selenium supplementation (100 microg/day) in pregnant women effectively reduces the incidence of PROM.

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.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Family tracing to identify patients with familial hypercholesterolaemia: the second audit of the Department of Health Familial Hypercholesterolaemia Cascade Testing Project.

BACKGROUND: Family tracing is a method recognized to find new patients with familial hypercholesterolaemia (FH). We have implemented family tracing led by FH Nurses and have determined acceptability to patients, feasibility and costs. METHODS: Nurses were located at five National Health Service (NHS) Trusts; they identified FH patients and offered them family tracing. Responses and test results were recorded on a database and summarized on a family pedigree. RESULTS: The majority ( approximately 70%) of index cases participated; the proportion was lower when patients had been discharged from the clinics and in metropolitan areas. On average, 34% (range 13-50%) of relatives lived outside the catchment area of the clinics and could not attend the nurse-led FH clinics. Of the previously untested relatives, 76% who lived in the catchment area of the clinic came forward to be tested. One-third of the relatives who came forward for testing were children

Prevalence of obesity and its association with socioeconomic factors in elderly Iranians from Razavi-Khorasan province.

There are few data regarding the prevalence of obesity and its socioeconomic determinants among elderly individuals, particularly in Iran. We wished to determine the prevalence of overweight and obesity in free-living elderly people and the relationship to nutritional and socioeconomic factors in the Razavi-Khorasan province of Iran. Free-living elderly persons (917 males/1045 females), aged > or =60 years, were recruited using cluster sampling. Overweight and obesity were evaluated using body mass index (BMI) and subjects were categorized as thin (BMI <18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2). The association between the prevalence of overweight or obesity with socioeconomic and demographic factors, including gender, place of residence, literacy, type of living, source of income, use of supplements during the past 3 months, and employment status, was examined using regression analysis. The distribution of BMI values indicated that 13, 46.5, 28.9, and 11.7% of the total population were thin, normal, overweight, and obese, respectively. The prevalence of central obesity was higher among Iranian women than men (63.1 vs. 18.6%, respectively). Regression analysis results indicated that gender (p < 0.001), place of residence (p < 0.001), literacy (p = 0.01), and source of income (p < 0.001) were significantly associated with the incidence of overweight or obesity. This study showed that 40.6% of elderly subjects were overweight or obese. Results reinforce the need to plan strategies for primary prevention of this fast-growing public health problem.

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.

Are patients with familial hypercholesterolaemia well managed in lipid clinics? An audit of eleven clinics from the Department of Health Familial Hypercholesterolaemia Cascade Testing project.

BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder which is relatively common, leads to high levels of LDL-cholesterol and if untreated to early coronary heart disease. An audit of current practice at National Health Service Trusts in England was undertaken to determine whether FH patients meet the diagnostic criteria for FH; are being offered appropriate advice and treatment; and to what extent their families are contacted and offered testing for the disorder. METHODS: Medical records of known FH patients (over 18 years of age and diagnosed before 31 December 2003) were accessed to obtain information on diagnosis, treatment and family tracing. RESULTS: The records of 733 FH patients were examined, 79% met the UK 'Simon Broome' register criteria for the diagnosis of definite or possible FH. Analyses showed that patients were usually offered appropriate advice and treatment, with 89% being on a statin. However, the audit indicated a high variability in family tracing between the sites, with significant differences in the frequency of inclusion of a family pedigree in the notes (range 1-71%, mean 35%); the general practitioner (GP) being advised that first-degree relatives should be tested (range 4-52%, mean 27%); and the proportion of relatives contacted and tested (range 6-50%, mean 32%). CONCLUSION: FH patients are well cared for in lipid clinics in England, are being given appropriate lifestyle advice and medication, but an increase in recording of LDL-cholesterol levels may lead to improvements in their management. Practice in family tracing appears to vary widely between clinics.

Natural honey and cardiovascular risk factors; effects on blood glucose, cholesterol, triacylglycerole, CRP, and body weight compared with sucrose.

It has been found that honey ameliorates cardiovascular risk factors in healthy individuals and in patients with elevated risk factors. The present study investigated the effect of natural honey on total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triacylglycerole, C-reactive protein (CRP), fasting blood glucose (FBG), and body weight in overweight individuals. There were 55 patients, overweight or obese, who were randomly recruited into the study and assigned into two groups: control group (17 subjects) and experimental group (38 subjects). Patients in the control group received 70 g of sucrose daily for a maximum of 30 days and patients in the experimental group received 70 g of natural honey for the same period. In the control and experimental groups, body weight, body mass index, body fat weight, total cholesterol, LDL-C, HDL-C, triacylglycerole, FBG, and CRP were measured before treatment and at day 31 after the commencement of treatment. Results showed that honey caused a mild reduction in body weight (1.3%) and body fat (1.1%). Honey reduced total cholesterol (3%), LDL-C (5.8), triacylglycerole (11%), FBG (4.2%), and CRP (3.2%), and increased HDL-C (3.3%) in subjects with normal values, while in patients with elevated variables, honey caused reduction in total cholesterol by 3.3%, LDL-C by 4.3%, triacylglycerole by 19%, and CRP by 3.3% (p < 0.05). It is our conclusion that consumption of natural honey reduces cardiovascular risk factors, particularly in subjects with elevated risk factors, and it does not increase body weight in overweight or obese subjects.

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.

Serum hs-CRP varies with dietary cholesterol, but not dietary fatty acid intake in individuals free of any history of cardiovascular disease.

The objective of this study was to investigate whether serum high-sensitivity C-reactive protein (hs-CRP) concentration varies with dietary fatty acid intake in Iranian adults free of any history of cardiovascular disease (CVD). This cross-sectional study involved 8105 adults (3142 men) aged 35-65 years. Dietary intake was assessed using 24-h dietary recalls. The relationship between anthropometric, cardiometabolic risk factors and dietary data and serum hs-CRP was assessed using SPSS software. Median crude dietary saturated fat decreased across hs-CRP quarters (P =0.009 for linear trend), whereas energy-adjusted total fat (P =0.017), trans-fat (P =0.016), monounsaturated fatty acids (P =0.030) and cholesterol (P =0.005) monotonically increased, with some evidence of statistical interactions by gender. In conclusion, serum hs-CRP concentrations were associated with some components of dietary fatty acid intake in our population of individuals without CVD, suggesting that dietary fat intake could be associated with subclinical inflammation.

Serum high-sensitivity C-reactive protein as a biomarker in patients with metabolic syndrome: evidence-based study with 7284 subjects.

BACKGROUND/OBJECTIVES: Metabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, hypertension and glucose intolerance, and is associated with an increased risk of developing cardiovascular disease (CVD), diabetes mellitus and related diseases. Circulating levels of inflammatory markers such as C-reactive-protein (CRP) have reported to be associated with CVD. Against this background, the prevalence of MetS is increasing globally, and thus predictive biomarkers are required for identification of MetS patients at an increased risk. Here we explored the value of CRP as a biomarker in 7284 subjects and also investigated which features of MetS have the greatest association with the hs-CRP level. SUBJECTS/METHODS: The subjects were recruited from the Mashhad stroke and heart atherosclerotic disorder study. Anthropometric factors and biochemical parameters (for example, high-sensitivity CRP (hs-CRP), high-density lipoprotein/low-density lipoprotein, triglycerides (TGs) and fasting blood glucose (FBG)) were determined. Univariate and multivariate analyses were conducted to evaluate the association of hs-CRP and MetS. RESULTS: Our results illustrated that the concentration of serum hs-CRP increased progressively with the number of MetS components, and subjects who fulfilled the criteria of MetS for waist circumference, TGs, blood pressure and FBG were found to have hs-CRP of 0.53, 0.38, 0.34 and 0.71 mg/l, respectively, higher than matched-subjects. Importantly, FBG had the greatest association with hs-CRP concentration. CONCLUSIONS: Our data demonstrate the significant association between MetS components with hs-CRP, indicating that this association was cumulative by increasing the number of the defining features of MetS, supporting further studies to explore the value of emerging marker as a novel method for detecting individuals at high risk of developing MetS.

The effects of LPS and probucol on interleukin 1 (IL-1) and platelet-derived growth factor (PDGF) gene expression in the human monocytic cell line U-937.

We have investigated the effects of lipopolysaccharide (LPS) and probucol (a lipid soluble antioxidant) on the gene expression of interleukin 1 alpha and beta (IL-1 alpha and IL-1 beta), and platelet-derived growth factor A chain and B chain (PDGF-A and PDGF-B) in the human monocytic cell line U-937. Steady-state mRNA levels were measured quantitatively by the reverse transcription-polymerase chain reaction (RT-PCR) using a non-radioactive label. Cells were incubated with LPS, in the presence or absence of probucol for 20 h. The cells were harvested and RNA was then prepared, reverse-transcribed in the presence of an internal standard and subsequently amplified and labelled with digoxigenin-11-dUTP by the PCR reaction. The PCR products were subjected to agarose gel electrophoresis, blotted onto nylon membranes and visualised by immunological detection of digoxigenin followed by a chemiluminescent reaction. We found that: (1) LPS treatment of U-937 cells caused an up-regulation of gene expression of IL-1 beta and PDGF-A chain by approximately 250% and 100% respectively, although it did not stimulate the expression of IL-1 alpha nor PDGF-B chain mRNA. (2) Probucol treatment in vitro had no effect on the basal or LPS-stimulated mRNA levels of IL-1 alpha, IL-1 beta, PDGF-A and PDGF-B despite its reported activity in vivo. (3) PDGF-A and PDGF-B were expressed at a similar level in unstimulated U-937 cells approximately 10-50 copies/ng total RNA, whereas the expression of IL-1 beta mRNA was approximately 2-4 times higher than IL-1 alpha mRNA. (4) Finally, in U-937 monocytic cells the expression of IL-1 alpha and IL-1 beta, and PDGF-A and PDGF-B appear to be independently regulated.

Oxidative modification of low-density lipoprotein by human polymorphonuclear leucocytes to a form recognised by the lipoprotein scavenger pathway.

The oxidative modification of low-density lipoprotein (LDL) results in the formation of cytotoxic and chemotactic lipids which are thought to be of importance in the development of atherosclerotic lesions. In the present study we show that polymorphonuclear leucocytes (PMNs) can modify LDL to a form which is rapidly incorporated by macrophages via a scavenger receptor pathway. Incubation of 125I-labelled LDL with PMNs in Ham's F-10 medium resulted in oxidation as shown by the appearance of thiobarbituric acid-reactive substances, increased electrophoretic mobility of the LDL and increased degradation of the LDL by mouse peritoneal macrophages. The presence of the anti-oxidant butylated hydroxytoluene or the metal ion chelator, EDTA inhibited the PMN-mediated modification. The degradation of 125I-labelled PMN modified LDL by macrophages was competitively inhibited by unlabelled copper-oxidised LDL but not by native LDL, indicating that the degradation was mediated by the scavenger receptor. The oxidative modification of LDL by PMNs could be of pathophysiological importance in inflammation and in the accelerated atherosclerosis seen following cardiac reperfusion injury.

Endogenous neutralizing antibodies against platelet-derived growth factor-aa inhibit atherogenesis in the cholesterol-fed rabbit.

Previous studies have shown that the B chain of platelet-derived growth factor (PDGF) has an important role in atherogenesis. In this study we have investigated the contribution of PDGF-A chain in cholesterol-induced atherogenesis in the New Zealand White rabbit. High titers of antibodies to PDGF-AA or to platelet cytosolic protein (PCP) were induced in these animals by immunization against recombinant human PDGF-AA or human PCP. Rabbits were then fed a 0.25% to 1% cholesterol-containing diet for 10 weeks to induce atherosclerotic lesions; the rabbits were then humanely killed and perfusion-fixed and their aortas were removed. The extent of atherosclerosis in the thoracic aortas was determined by quantitative morphometry after staining with oil red O. The intimal and medial areas in histological sections taken at the level of the first intercostal branch were quantified by image analysis. Immunization against PDGF-AA and PCP, but not against adjuvant alone, resulted in rising titers of antibodies within 2 weeks, the levels of which reached a plateau by 8 weeks. The antibodies to PDGF-AA were isoform-specific, recognized both human and rabbit PDGF-AA, and neutralized the biological activity of PDGF-AA in vitro. Integrated plasma cholesterol levels were similar in both groups. Compared with nonimmune rabbits (n=10), animals immunized against PDGF-AA (n=10) or PCP (n=10) had significantly smaller areas of the aorta covered by atherosclerotic lesions (24.6+/-5.1% and 18.7+/-4.2%, respectively, vs 34.4+/-4.3%; P<0.05). This was associated with a reduced aortic intimal-medial area ratio in PDGF-AA-immunized (0.009+/-0.006) and PCP-immunized (0.025+/-0.017) rabbits than in nonimmune animals (0.159+/-0.066; P<0.05). These data suggest that PDGF-AA is actively involved in cholesterol-induced atherosclerosis in the rabbit.

Determinants of serum copper, zinc and selenium in healthy subjects.

BACKGROUND: We have investigated the association between serum copper, zinc and selenium concentrations, dietary intake, and demographic characteristics, including individual coronary risk factors, in healthy subjects. METHODS: Serum copper, zinc and selenium were measured by atomic absorption spectrometry in 189 healthy subjects. Serum glutathione peroxidase and caeruloplasmin were also determined for each subject. A previously validated food frequency questionnaire was used to estimate the dietary trace element intake. RESULTS: Male subjects had significantly lower serum copper (P<0.001) and caeruloplasmin (P<0.001), and higher serum zinc (P<0.05) and zinc:copper ratio (P<0.001) than female subjects. Significant differences were observed in serum copper and caeruloplasmin concentrations (P<0.01) with age. Weak but significant associations between dietary trace elements and their serum concentrations were observed for zinc (r=0.18, P=0.02), copper (r=0.17, P=0.03) and selenium (r=0.19, P=0.02). Obese subjects had significantly lower serum concentrations of zinc (P<0.05). In multifactorial analysis, dietary zinc (P<0.05), serum high-density lipoprotein-cholesterol (HDL-C) (P<0.05), diastolic blood pressure (P<0.05) and age (P=0.05) emerged as major predictors of serum zinc concentrations. The corresponding predictors for serum copper were C-reactive protein (CRP) (P<0.001), serum HDL-C (P<0.001), gender (P=0.01), physical activity levels (P<0.05) and dietary copper (P<0.05). Serum selenium concentrations were predicted by serum total cholesterol (P<0.01), serum CRP concentrations (P<0.05) and dietary selenium (P<0.03). CONCLUSION: Serum copper, zinc and selenium concentrations are influenced by physiological conditions such as age, diet and gender. Their serum concentrations are also associated with coronary risk factors, including body mass index, levels of physical activity, serum HDL-C and CRP.