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Objectives: Despite advances in our understanding of metabolic syndrome (MetS) and the treatment of each of its components separately, currently there is no single therapy approved to manage it as a single condition. Since multi-drug treatment increases drug interactions, decreases patient compliance and increases health costs, it is important to introduce single therapies that improve all of the MetS components., Evidence Acquisition: We conducted a PubMed, Scopus, Google Scholar, Web of Science, US FDA, utdo.ir and clinicaltrial.gov search, gathered the most relevant preclinical and clinical studies that have been published since 2010, and discussed the beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors to prevent and treat different constituent of the MetS as a single therapy. Furthermore, the pharmacology of DPP-4 inhibitors, focusing on pharmacodynamics, pharmacokinetics, drug interactions and their side effects are also reviewed., Results: DPP-4 inhibitors or gliptins are a new class of oral anti-diabetic drugs that seem safe drugs with no severe side effects, commonly GI disturbance, infection and inflammatory bowel disease. They increase mass and function of pancreatic β-cells, and insulin sensitivity in liver, muscle and adipose tissue. It has been noted that gliptin therapy decreases dyslipidemia. DPP-4 inhibitors increase fatty oxidation, and cholesterol efflux, and decrease hepatic triglyceride synthase and de novo lipogenesis. They delay gastric emptying time and lead to satiety. Besides, gliptin therapy has anti-inflammatory and anti-atherogenic impacts, and improves endothelial function and reduces vascular stiffness., Conclusion: The gathered data prove the efficacy of DPP-4 inhibitors in managing MetS in some levels beyond anti-diabetic effects. This review could be a lead for designing new DPP-4 inhibitors with greatest effects on MetS in future. Introducing drugs with polypharmacologic effects could increase the patient's compliance and decrease the health cost that there is not in multi-drug therapy. Graphical abstract ᅟ.

Curcumin is the principal polyphenolic compound present in turmeric with broad applications in tissue engineering and regenerative medicine. It has some important inherent properties with the potential to facilitate tissue healing, including anti-inflammatory, anti-oxidant, and antibacterial activities. Therefore, curcumin has been used for the treatment of various damaged tissues, especially wound injuries. There are different forms of curcumin, among which nano-formulations are of a great importance in regenerative medicine. It is also important to design sophisticated delivery systems for controlled/localized delivery of curcumin to the target tissues and organs. Although there are many reports on the advantages of this compound, further research is required to fully explore its clinical usage. The review describes the physicochemical and biological properties of curcumin and the current state of the evidence on its applications in tissue engineering. © 2018 BioFactors, 45(2):135-151, 2019., (© 2018 International Union of Biochemistry and Molecular Biology.)

In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated. A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25 mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR. Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (-0.01 ± 0.24, -0.007 ± 0.52 vs. 1 ± 0.50, P = 0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (-0.24 ± 2.28, -4.49 ± 4.86 vs. 1 ± 0.50, P = 0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93 ± 0.17, 1.54 ± 0.17 vs. 0.51 ± 0.11; P ≤ 0.000). The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The anoxemia theory proposes that an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerosis. There is now substantial evidence that there are regions within the atherosclerotic plaque in which profound hypoxia exists; this may fundamentally change the function, metabolism, and responses of many of the cell types found within the developing plaque and whether the plaque will evolve into a stable or unstable phenotype. Hypoxia is characterized in molecular terms by the stabilization of hypoxia-inducible factor (HIF) 1α, a subunit of the heterodimeric nuclear transcriptional factor HIF-1 and a master regulator of oxygen homeostasis. The expression of HIF-1 is localized to perivascular tissues, inflammatory macrophages, and smooth muscle cells adjacent to the necrotic core of atherosclerotic lesions and regulates several genes that are important to vascular function including vascular endothelial growth factor, nitric oxide synthase, endothelin-1, and erythropoietin. This review summarizes the effects of hypoxia on the functions of cells involved in atherogenesis and the evidence for its potential importance from experimental models and clinical studies.

Background: Recent studies have shown that antibody titers to heat shock protein 27 (anti-Hsp27) and serum hs-CRP concentrations are elevated in patients with MetS, and may be associated with an increased risk of cardiovascular disease. Crocin is a natural carotenoid with cardio protective effects., Objective: Because of the previous evidence for the beneficial effects of saffron in patients with MetS, this study investigated the effect of supplementation with crocin, the active ingredient of saffron, on serum anti-Hsp27 and hs-CRP in patients with MetS., Design: Sixty subjects with metabolic syndrome were randomized to receive crocin (n=30, 15 mg twice a day) or placebo (n=30, twice a day) for a duration of eight weeks. At the end of study, serum anti-Hsp27 and hs-CRP concentrations were measured and compared between the groups., Results: Serum anti-Hsp27 titers fell by 13% (p>0.05) in the crocin group but it rose in the placebo group by 22% (p>0.05). The magnitude of change in serum anti-Hsp27 titers was not significantly different between the study groups (p = 0.28). In the crocin group, serum anti-Hsp27 changes had a borderline negative correlation with glucose (r= -0.35, p=0.06) and a positive correlation with waist circumference (r=0.39, p=0.035). Serum hs-CRP levels were significantly reduced in both groups but these reductions were not significantly different between the study groups (p = 0.31)., Conclusion: There was no significant effect of crocin on serum anti-Hsp27 titers in subjects with MetS, but this needs further confirmation in larger-scale trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Depression and anxiety are prevalent serious psychiatric disorders. Several drugs are used to treat these conditions but these are often associated with serious side effects. For this reason alternative therapies, including herbal medication such as saffron, have been proposed. We aimed to assess the effects of saffron extract for the treatment of anxiety and depression using a 12-week double-blind, placebo-controlled trial design., Methods: Sixty adult patients with anxiety and depression were randomized to receive a 50 mg saffron capsule (Crocus sativus L. stigma) or a placebo capsule twice daily for 12 weeks. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) questionnaires were used at baseline, 6 and 12 weeks after initiating medication. 54 subjects completed the trial., Results: Saffron supplements had a significant effect on the BDI and BAI scores of subjects in comparison to placebo at the 12 week time-point (p<0.001)., Conclusions: Saffron appears to have a significant impact in the treatment of anxiety and depression disorder. Side effects were rare.

Background: Perinatal asphyxia is an important cause of death, as well as permanent neurological and developmental complications. Diagnosing in time would lead to better prognosis and applying the most proper treatment. We sought to define the predictive values of serum concentrations of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in newborns with perinatal asphyxia to see if there is a relation between the short-term neurological deficit and serum IL-1β and IL-6 concentrations., Methods: This was a prospective (case-control) study conducted between March 2006 and April 2013, at the Neonatal Intensive Care Unit, Mashhad, Iran. Serum IL-1β and IL-6 levels were measured at birth in 38 consecutive uninfected neonates with perinatal asphyxia (blood pH < 7.2, low Apgar score, signs of fetal distress) and 47 randomly selected healthy newborns. The results were compared between the groups, using Chi-Square, t-tests, and Mann-Whitney tests, as well as receiver operator characteristics (ROC) curves and regression models., Results: Serum IL-1β and IL-6 concentrations in the infants who developed perinatal asphyxia were significantly higher compared to values in the normal infants [16.88 vs  3.34 pg/mL for IL-1β, (P = 0.006), and 88.15 vs 6.74 pg/ mL for IL-6, (P < 0.001) respectively]. The sensitivity and  specificity for the diagnosis of perinatal asphyxia using serum IL-6 were 80.5% and 81.6% respectively. The sensitivity and specificity using serum IL-1β were 71% and 89.1%, respectively., Conclusion: Evaluating serum IL-6 and 1β simultaneously, could improve the sensitivity and specificity of early diagnosis of the perinatal  asphyxia. The most appropriate indicator of perinatal asphyxia is combined measurement of interleukin 1β and interleukin 6.

Metabolic syndrome is an important risk factor for cardiovascular disease (CVD). The heat shock proteins (HSPs) are associated with risk factors for CVD. The aim of the present study was to survey the effect of barberry on antibody titres to HSPs and high-sensitivity C-reactive protein (hs-CRP) in patients with metabolic syndrome. In our study, subjects (N=106, 79 women and 27 men, 18-65 years old) with metabolic syndrome were randomized into two groups: a group of patients who received three capsules of barberry and a control group who received three capsules of placebo for 6 weeks. Antibodies against HSPs 27, 60/65 and 70, hs-CRP and lipid profile were determined in patients before (week 0) and after (week 6) intervention. spss software (version 16.0; Inc, Chicago, IL) was used for data analysis. Results showed that barberry had no significant effect on serum level of anti-HSPs 65 and 70. But there was a significant decrease in anti-HSP 27 in both case and control groups (p=0.001 and p<0.001, respectively, in the case and control groups). Barberry decreased significantly anti-HSP 60 in the case group (p=0.03). High-sensitivity CRP was decreased non-significantly (p=0.17) in the case group and increased significantly (p=0.04) in the control group. Barberry decreased significantly low-density lipoprotein and total cholesterol and increased significantly high-density cholesterol (p<0.05). Results of the present study suggested that barberry supplementation in patients with metabolic syndrome decreased significantly anti-HSPs 27 and 60 and hs-CRP levels and improved lipid profile., (Copyright © 2014 John Wiley & Sons, Ltd.)

Atherosclerosis is the leading global cause of mortality, morbidity, and disability. Heat shock proteins (HSPs) are a highly conserved family of proteins with diverse functions expressed by all cells exposed to environmental stress. Studies have reported that several HSPs may be potential risk markers of atherosclerosis and related cardiovascular diseases, or may be directly involved in the atherogenic process itself. HSPs are expressed by cells in atherosclerotic plaque and anti-HSP has been reported to be increased in patients with vascular disease. Autoimmune responses may be generated against antigens present within the atherosclerotic plaque, including HSP and may lead to a cycle of ongoing vascular injury. It has been suggested that by inducing a state of tolerance to these antigens, the atherogenic process may be limited and thus provide a potential therapeutic approach. It has been suggested that anti-HSPs are independent predictors of risk of vascular disease. In this review, we summarize the current understanding of HSP in cardiovascular disease and highlight their potential role as diagnostic agents and therapeutic targets.

Breath analysis is becoming increasingly established as a means of assessing metabolic, biochemical and physiological function in health and disease. The methods available for these analyses exploit a variety of complex physicochemical principles, but are becoming more easily utilised in the clinical setting. Whilst some of the factors accounting for the biological variation in breath metabolite concentrations have been clarified, there has been relatively little work on the dietary factors that may influence them. In applying breath analysis to the clinical setting, it will be important to consider how these factors may affect the interpretation of endogenous breath composition. Diet may have complex effects on the generation of breath compounds. These effects may either be due to a direct impact on metabolism, or because they alter the gastrointestinal flora. Bacteria are a major source of compounds in breath, and their generation of H2, hydrogen cyanide, aldehydes and alkanes may be an indicator of the health of their host.

Background and Aim of the Study: Cardiopulmonary bypass (CPB) is used during on-pump coronary artery bypass grafting (CABG) and heart valvular replacement surgery, and is associated with the induction of oxidative stress. The aim of the study was to assess the association between indices of cardiac function and prooxidant-antioxidant balance (PAB) values in patients undergoing valve replacement surgery and on-or off-pump CABG., Methods: Data were obtained from 44, 33, and 41 patients undergoing off-pump CABG, on-pump CABG, and valve replacement surgery, respectively. The PAB values were measured 24 h before and after the operative procedure, and at the time of discharge. Echocardiography was performed before surgery and before discharge., Results: The changes in E/E', end-diastolic volume, end-systolic volume, left ventricular diastolic and systolic diameter were significantly related to baseline PAB values. In the valve replacement group, neither baseline nor changes in PAB values were associated with echocardiographic measurements. Also, neither off-pump nor on-pump CABG were significantly different in inducing oxidative stress (p = 0.596). When PAB values were measured in CABG patients, there was a significant difference in values between the three time points (p = 0.013). In the valve replacement group, PAB values were not significantly different between the preoperative and postoperative samples., Conclusion: The inverse association between the level of oxidative stress and cardiac function measurement may indicate that high levels of oxidative stress may be a predictor of the deterioration of cardiac function in CABG patients. However, in valvular heart disease patients the serum PAB value was not associated with changes in cardiac function. Levels of oxidative stress, as assessed by the PAB assay, were not significantly different for patients undergoing surgery with or without CPB.

Objective: Determination of the serum heat shock protein 27 (Hsp27) antibody titers and prooxidant-antioxidant balance (PAB) in patients with thalassemia as markers of cell and oxidative stress, respectively., Methods: Serum PAB and anti-Hsp27 antibody titers were measured in 140 patients with thalassemia major and 140 sex- and age-matched healthy volunteers., Results: A significantly higher serum PAB value was observed in patients in comparison to controls. In the patient group, anti-Hsp27 antibody titers were significantly higher than for the control group (p < 0.001). We found a weak negative correlation between anti-Hsp27 antibody concentrations and the PAB (p = 0.03), but these values were not correlated with serum superoxide dismutase activity in the thalassemic patients., Conclusions: Increased levels of serum PAB and Hsp27 antibodies may be involved in the pathological consequences of β-thalassemia major and may contribute to the development of endothelial injury., (Copyright © 2012 S. Karger AG, Basel.)

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant-antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P < .05). The PAB values were significantly higher in cases (134.67 ± 13.69 Hamidi-Koliakos(HK) unit) when compared with controls (49.78 ± 6.75 HK unit; P < .05). In cases, the ejection fraction was inversely correlated with anti-Hsp-27 antibody (P < .05) but was not significantly related to PAB values (P > .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis.

Objectives: A randomized controlled clinical trial was performed to examine the effectiveness of auricular acupuncture on body weight loss and its impact on lipid profile, and immunologic and inflammatory markers in obese subjects., Methods: Participants (n=204) were randomized to therapeutic acupuncture and control groups. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks (first period) in combination with a low-calorie diet. In the next 6 weeks (second period), the low-calorie diet was used on its own. Subjects were assessed at the beginning and 6 and 12 weeks later. In addition to anthropometric and lipid parameters, serum anti-heat shock protein (Hsp)-27, 60, 65, 70 and high sensitive C-reactive protein (hs-CRP) levels were assessed., Results: In the first period, anthropometric parameters and hs-CRP changed significantly in both groups, while significant changes in anti-Hsp antibodies were only observed in case subjects. In the second period, which shows the sustainable effects of acupuncture, changes in anthropometric parameters were more prominent in controls, while significant reductions in the group receiving authentic acupuncture were maintained for anti-Hsp antibodies. A comparison between the first and second period in both groups showed that the changes for most of the parameters were more significant in the first period. Comparison between cases and controls showed that authentic acupuncture was more effective in reducing the levels of anthropometric factors and anti-Hsp antibodies but not hs-CRP., Conclusions: Auricular acupuncture in combination with diet restriction was effective for weight loss and dyslipidemia. Moreover, it was found that it has immunomodulatory but not anti-inflammatory effects on the immune system by regulation of the levels of anti-Hsp antibodies.

Heat shock proteins (Hsps) comprise several families of proteins expressed by a number of cell types following exposure to stressful environmental conditions that include heat, free radicals, toxins and ischemia, and are particularly involved in the recognition and renaturation of mis-folded proteins. Heat shock protein-27 (Hsp27) is a member of the small Hsp (sHsp) family with a molecular weight of approximately 27 KDa. In addition to its chaperoning functions, Hsp27 also appears to be involved in a diverse range of cellular functions, promoting cell survival through effects on the apoptotic pathway and plays important roles in cytoskeleton dynamics, cell differentiation and embryogenesis. Over the past two decades there has been an increasing interest in the relationship between Hsp27 and cardiovascular disease. Hsp27 is thought to exert an important role in the atherosclerotic process. Serum Hsp27 concentrations appear to be a biomarker of myocardial ischemia. In this review, we will focus on the possible protective and immuno-modulatory roles of Hsp27 in atherogenesis with special emphasis on their changes following acute coronary events and their potential as diagnostic and therapeutic targets., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We assessed the association between serum heat shock protein 27 (Hsp-27)concentrations in patients with acute coronary syndrome (ACS) and compared them with healthy participants. Patients with ACS (n = 75) were recruited and their biochemical parameters were compared with 75 healthy participants. Heat shock protein 27 concentrations were measured from blood samples taken on admission and 12 hours after the onset of chest pain. In the patient group, Hsp-27 concentrations (31.62 [20.12-38.51] ng/mL) in the first blood samples were significantly (P < .001) higher than in control samples (20.12 [16.67-28.17] ng/mL). In patients, serum Hsp-27 levels on admission were significantly (P < .001) higher than for the samples collected 12 hours after the onset of chest pain (25.87 [15.52-31.62]); the latter did not differ significantly from samples of healthy controls. In conclusion, serum Hsp-27 concentrations are elevated in the early hours following ACS, but fall to levels near to those in healthy individuals after about 12 hours from the onset of chest pain.

A randomized controlled clinical trial in 196 obese subjects was performed to examine the effectiveness of body acupuncture on body weight loss, lipid profile and immunogenic and inflammatory markers. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Subjects were assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps)-27, 60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP) levels were also assessed. A significant reduction in measures of adiposity and improvement in lipid profile were observed in both groups, but the levels of anti-Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid profile in cases were sustained in the second period, however, only changes in lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP levels continued to be reduced in cases but in controls only the reduction in hs-CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp-antibodies were more evident in cases. Body acupuncture in combination with diet restriction was effective in enhancing weight loss and improving dyslipidemia.

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD)., Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients., Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05)., Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: We have assessed the relationship between indices of adiposity and antibody titers to Hsp-27 in healthy subjects., Design: Two-hundred and fifty subjects were studied, including 50 normal-weight subjects (body-mass-index (BMI) 25 kg/m(2)), 100 overweight subjects (BMI 25 to 30 kg/m(2)) (n=100) and 100 obese subjects (BMI ≥ 30 kg/m(2))., Results: Anti-Hsp27-antibody levels in obese subjects were [0.34 (0.20-0.39) absorbency unit], being significantly higher than overweight and normal-weight groups (P<0.05). Anti-Hsp27-antibody levels in overweight subjects [0.29 (0.15-0.34) absorbency unit] were statistically higher than controls [0.18 (0.10-0.23) absorbency unit] (P<0.05)., Conclusion: High anti-Hsp-27-antibody levels in obese-subjects without established coronary disease may be related to a heightened state of immunoactivation associated with obesity., (Copyright © 2011 The Canadian Society of Clinical Chemists. All rights reserved.)

Although it has been known for centuries that there are compounds in exhaled breath that are altered in disease, it is only in the last few decades that it has been possible to measure them with sufficient accuracy and precision to make them clinically useful. The clinical utility of breath analysis has also been limited by the practical difficulties of collecting representative breath samples, free from contaminants. More recent methods of breath analysis have allowed real-time analysis of breath, eliminating the need for sample collection, and therefore potentially allowing the rapid feedback of results to patient and clinician. One possible future application of breath analysis may be the monitoring of metabolic control in patients with diabetes mellitus. This perspective article provides an overview of the studies of breath analysis in diabetes, focusing on the breath metabolites; acetone, isoprene and also methyl nitrate that have previously been reported to be altered in diabetes, highlighting the factors that may potentially confound their interpretation. Specific attention is given to selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS), because they are techniques that have been developed specifically for the absolute quantification of breath metabolites in real time, although reference is made to some of the alternative techniques, including sensors and optical devices. Whilst breath analysis, using SIFT-MS, PTR-MS and other sensitive techniques, can potentially be used for the non-invasive monitoring of metabolic conditions that may include diabetes mellitus, further work is required in terms of the clinical and analytical validation. Furthermore, it is unclear at present what breath metabolites should be monitored and what factors may confound their interpretation. Although a non-invasive method of monitoring glycaemic control is clearly desirable, it will be important to demonstrate its analytical comparability with the well-established and validated methods for blood glucose measurement.

Background: There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients., Methods: Patients with angiographically defined coronary artery disease (CAD) (n=309) were evaluated for the presence of AT(1)R/A1166C polymorphism. These patients were classified into subgroups with (n=164, M/F: 109/55) and without (n=145, M/F: 84/61) diabetes mellitus. The AT(1)R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method., Results: There was a higher frequency of polymorphic genotypes (AC+CC) in the diabetic compared with the non-diabetic group (p=0.01). When determined for each gender separately, this difference remained significant in the males (p=0.04) but not in females (p=0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p=0.01). This remained significant after gender segregation for males (p=0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (β=1.16, p<0.001 for total population and β=1.29, p<0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p=0.04)., Conclusion: The AT(1)R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.

Objective: This study aimed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins (HSPs) in dyslipidemic patients., Design and Methods: Participants (n=102) were treated with simvastatin (40mg/day), or placebo in a randomized, double-blind, placebo-controlled, cross-over trial. Anti-HSP60, 65, 70, and hs-CRP levels were measured before and after each treatment period. Seventy-seven subjects completed the study., Results: Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p<0.001). There have been previous reports of reductions in serum CRP with statin treatment, and although median CRP levels were 9% lower on simvastatin treatment, this did not achieve statistical significance., Conclusion: While it is unclear whether HSP antibodies are directly involved in atherogenesis, our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease., (Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis. Immune complexes (ICs) may form between these antigens and autoantibodies and via Fc receptor signaling and complement activation may modulate the inflammation in atherosclerosis. Antibody isotype may direct the role that ICs play in atherogenesis, immunoglobulin G (IgG) being potentially pro-atherogenic and immunoglobulin M (IgM) playing a protective role. Therapeutic options targeting complement activation and those which are potentially Fc-receptor mediated have been investigated in animal models, though targeting Fc receptor signaling is an area that needs further investigation.

Serum heat shock protein 27 immunoglobulin G (IgG) antibody titers (anti-HSP27) and high-sensitivity C-reactive protein (hsCRP) concentrations were measured in samples from 168 patients in the first 24 hours after the onset of stroke and 80 age-and sex-matched control participants. In patients with stroke, median serum anti-HSP27 titer was significantly higher than that of the control group (0.18 [0.14-0.28] vs 0.08 [0.04-0.12], P < .001). Median serum hsCRP concentration was also significantly higher in patients compared with the control group (11.43 [8.07-13.53] vs 3.23 [1.66-6.24], P < .001). Serum anti-HSP27 and hsCRP concentrations did not differ significantly among patients with different stroke types. Neither serum anti-HSP27 nor hsCRP levels predicted 6-month prognosis in the patients with stroke. We conclude that serum anti-HSP27 titers and hsCRP concentrations are elevated in patients with stroke but do not distinguish between stroke types or predict 6-month prognosis.

Introduction: Neonatal hypernatermic dehydration (NHD) is a potentially very serious condition, which has been reported to occur in infants who have breast feeding problems in the first week of the life. This study looked at the incidence, risk factors, clinical symptoms and complications of NHD in healthy breastfed term neonates., Methods: A prospective case-control study was conducted on 53 neonates with serum sodium concentrations of >or=150 mmol/L (as the case group) who were recruited between June 2006 and June 2007 from the Ghaem hospital (Mashhad, Iran) to investigate the relationship between NHD and breastfeeding. Fifty-three healthy breastfed full-term neonates (serum sodium<150 mmol/L) from the same hospital were also recruited as the control group., Result: The results showed an average weight loss of 1.6% in the healthy neonates vs. 16.2% in infants with NHD (p<0.001). The frequency of feeds received per day was 10.2 for the healthy neonates vs. 7.6 in the NHD group (p<0.001). The NHD group had mothers who had a higher frequency of breast problems (23 vs. 7, p<0.001). Mean serum sodium concentration was significantly lower in the control group compared with the cases (137.80 vs.160.06 mmol/L, p<0.001). The main presenting features of the infants with NHD were fever, lethargy and jaundice., Conclusion: Breastfeeding problems are associated with the presence of NHD. Therefore, more breast examination during prenatal and postnatal periods and careful neonatal weight watch during the first week of life could decrease the incidence of NHD.

Chromium deficiency is associated with impaired glucose tolerance (IGT) and dyslipidemia. Hence, the objective of the current study was to investigate chromium status among Saudi men with and without established cardiovascular disease (CVD) and its relationship to glucose tolerance, lipid profile and other established CVD risk factors. We measured serum and urine chromium concentrations, fasted lipid profile, plasma glucose, and serum lipid peroxide in 130 Saudi men with an established history of myocardial infarction and 130 age-matched controls without established CVD. Patients with established CVD had higher serum triglycerides (p < 0.05) and plasma glucose (p < 0.0001) and lower serum and urinary chromium concentrations (p < 0.0001) than controls. Serum chromium was inversely correlated with plasma glucose among cases and controls (r = -0.189, p < 0.05 and r = -0.354, p < 0.00001, respectively). Plasma glucose (OR 1.127, CI 1.0-1.269, p < 0.05), serum chromium (OR 0.99, CI 0.985-0.995, p < 0.0001), and urinary chromium (OR 0.988, CI 0.981-0.995, p < 0.001) were independently associated with the presence of established coronary disease applying this model. While chromium metabolism appears to be altered in individuals with CVD, it is unclear whether chromium supplementation would be effective in CVD prevention among patients with IGT. This would need to be tested in long-term outcome trials.

Objective: Fish-oil contains high concentrations of omega-3 fatty acids that have been shown to have anti-inflammatory properties. We have evaluated the effects of purified omega-3 fatty acid supplements on several anthropometric and biochemical parameters, including heat shock protein (Hsp) 27 antibody titres in subjects with metabolic syndrome., Methods: Subjects (n = 120) with metabolic syndrome (mean age of 52.9 +/- 11.9 years) were randomly allocated to one of two groups: sixty subjects were given 1 gram of fish oil as a single capsule, containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid daily for 6 months. Control subjects did not receive any supplementation over the same period., Results: The study was completed by 47 subjects in the intervention group and 42 subjects in the control group. Treatment with omega 3 supplements was associated with a significant fall in body weight (P < 0.05), systolic blood pressures (P < 0.05), serum low density lipoprotein cholesterol (P < 0.05), and total cholesterol (P < 0.05), triglycerides (P < 0.05), high-sensitivity C-reactive protein (hs-CRP) (P < 0.01), and Hsp27 antibody titres (P < 0.05). No significant changes were observed in the control group., Conclusion: It appears that omega 3 improves the cardiovascular risk profile of subjects with metabolic syndrome, having effects on weight, systolic blood pressure, lipid profile and markers of inflammation and autoimmunity.

The inability of two definitions of metabolic syndrome (MS) to predict the presence of coronary artery disease (CAD) in a non-Caucasian population was demonstrated. Angiography was used as the gold standard method for identifying patients with (cases) or without (controls) CAD. It is possible that the current definitions of MS are not appropriate for some non-Caucasian populations.

The purpose of this research was to investigate the relationship between selenium levels, thyroid function and other coronary risk factors in 140 Saudi subjects without overt coronary heart disease stratified by age. Demographic data and serum fasting lipid profile, glucose, thyroid function tests, selenium status and dietary intake was assessed. The relationships between selenium status, thyroid function and cardiovascular risk factors were assessed by univariate and multivariate analysis. The results showed that thyroid hormone levels did not differ with age. Erythrocyte glutathione peroxidase (GPx) levels were significantly higher in the youngest vs. oldest tertile (p<0.0001). Selenium and iodine intake did not differ significantly with age tertile, but the average intake for the population sample was below the estimated average requirements for both elements. Serum lipoprotein (a) concentrations correlated with selenium (r = 0.417, p<0.0001) and TSH (r = 0.172, p<0.05). After adjustment for confounding variables; serum fT(4) and erythrocytes GPx remained significant determinants of serum TSH levels, whilst serum selenium and TSH were determinants of serum fT(4) levels. Serum Lp(a), a coronary risk factor, was strongly related to measures of selenium status. A significant relationship between measures of selenium status and thyroid function was found. Serum Lp(a) a known risk factor for cardiovascular disease was also related to selenium status in our population.

Cardiovascular risk factors are individually only modest predictors of events, and whilst more sophisticated algorithms appear to improve their prediction, a significant proportion of the population is miscategorised and therefore managed inappropriately. It is proposed that atherogenesis is a multi-step process, and that the critical transitions between steps requires 'bundles' of risk factors that may differ for each step. These bundles may not always contain a classical risk factor and may differ between individuals. This hypothesis would predict that the impact of specific risk factors is non-uniform during atherogenesis and therefore the efficacy of interventions will vary with stage. New therapeutic opportunities exist if the factors that promote progression between particular stages could be identified and targeted. The staging of disease using modalities such as imaging and functional assessment may be necessary to deliver the most effective treatment. Finally, risk assessment will invariably be inaccurate, even using complex algorithms.

Morphological and immunocytochemical studies have elucidated the complex processes involved in atherogenesis. The notion of plaque instability has emerged from this work and underscored the importance of inflammation in determining clinical complications associated with atherosclerosis, such as acute coronary syndrome. Cells of the immune system have been detected within atherosclerotic lesions and auto-antibodies directed against modified LDL and heat-shock proteins have been identified in the blood of individuals with atherosclerosis. The use of risk 'engines', e.g. the Framingham coronary risk score, has facilitated the identification of individuals at high risk, but the constituent classical risk factors used in these algorithms do not adequately differentiate individuals at moderate risk. As age is a major component of the equations used in these algorithms they are not particularly useful in young adults, and their applicability to non-Caucasian populations has been questioned. Biomarkers of early disease and plaque instability have therefore both been sought. Although some of these markers have been shown individually to be associated with a significant hazard ratio, no substantial improvement in discrimination has been demonstrated when they are incorporated into a risk 'engine'. The latter has generally been assessed by receiver operator characteristic curve analysis, although this approach has been criticised. Other modalities, including imaging and functional assessments of vascular function, are now being developed for clinical use.

Introduction: Aspects of trace element status have previously been investigated as possible contributory factors to atherosclerosis. In this present study a more comprehensive approach has been taken, looking at the relationship between dietary macro- and micronutrient intake, serum concentrations of zinc and copper, and markers of inflammation in dyslipidaemic patients with or without established coronary artery disease (CAD) and healthy controls, so that a clearer understanding of the potential relationship between copper and zinc status and coronary disease may be ascertained., Methods and Materials: Dyslipidaemic patients (n = 238) were recruited from the local General Hospital in Guildford, UK. Fifty-five of these patients had established CAD. Control subjects (n = 135) were recruited from among employees at the local University and Hospital. A validated food frequency questionnaire was used for estimating the dietary intake of zinc and copper., Results: Serum copper, copper/caeruloplasmin ratio, zinc/copper ratio, and C-reactive protein (CRP) were significantly different in the patient groups compared to controls [serum copper: 17.20 +/- 0.2 v 15.91 +/- 0.29 micromol/L, p < 0.001; copper/caeruloplasmin ratio: 111.37 +/- 2.18 v 100.63 +/- 2.93 micromol/g, p < 0.01; zinc/copper ratio: 0.85 +/- 0.01 v 0.90 +/- 0.01, p < 0.05; and CRP: 1.25 (0.42-3.26) v 0.58 (0.17-1.42) mg/L, p < 0.001]. Dietary protein, total fat, starch, fibre, monounsaturated fat, zinc, and zinc/copper ratio were also significantly higher in the patients compared to controls. Patients with established CAD had significantly higher serum CRP (p < 0.05) and lower serum zinc (p < 0.01) and zinc/copper ratio (p < 0.01) compared to both patients without CAD and healthy controls., Conclusion: Significant differences in copper and zinc status, dietary intake and markers of inflammation were observed in patients with dyslipidaemia, with or without established CAD, compared with control subjects. Differences in serum CRP, copper and caeruloplasmin may be related to a heightened state of inflammation. The imbalance in zinc/copper metabolism may either contribute to the CAD risk or be a consequence of an acute phase response.

Epidemiological studies have shown an association between atherosclerosis, Heat shock protein (Hsp) expression, and Hsp antibody titres. We aimed to investigate the time course of appearance of Hsp-60, -65 and -70 antibodies in the cholesterol-fed rabbit and to relate antibody titres to serum concentrations of von Willebrand factor (vWF), a marker of endothelial injury. Rabbits were fed with 0.25-1.0% cholesterol diet for 13 weeks. Plasma levels of anti Hsp-60, -65 and -70 IgG titres, were measured using in-house enzyme-linked immunosorbent assays (ELISAs) together with plasma vWF concentrations. Plasma titres of anti-Hsp-60, -65 and -70 antibodies were all significantly increased by weeks 5, 7 and 9 following commencement of the experimental diet compared with baseline (P < 0.05 for all). In non-cholesterol-fed rabbits, plasma levels of anti-Hsp titres were unchanged over this period. Increased plasma vWF concentrations were also found in the cholesterol-fed rabbits, reaching a maximum at approximately week 8, and falling thereafter. Furthermore, plasma vWF concentrations at 13 weeks correlated strongly with antibody titres to all three Hsps (r = 0.90, P = 0.002; r = 0.80, P = 0.017; r = 0.86, P = 0.006 for Hsp 60, -65 and -70 respectively) and titres were also strongly correlated with final plasma cholesterol concentrations in cholesterol-fed animals (r = 0.95, P = 0.002; r = 0.8, P = 0.001; r = 0.84, P = 0.01 respectively). In cholesterol-fed rabbits, antibody titres to Hsp-60, -65 and -70 appear to rise in association with a marker of endothelial injury, peaking at approximately the same time (8 weeks) after starting a high cholesterol diet.

Insulin resistance is a common condition, recognized to be a central feature of the metabolic syndrome, and strongly associated with an increased risk of cardiovascular disease and diabetes. The quantitative assessment of insulin sensitivity is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, aetiology and consequences. The gold standard method for the determination of insulin sensitivity is the euglycaemic hyperinsulinaemic clamp from which indices of insulin sensitivity can be derived. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. Indices can also be derived from measurements made during a standard oral glucose tolerance test and from one-off fasting specimens (e.g. homeostasis model assessment and quantitative insulin sensitivity check index). These indices lend themselves for use in large population studies where a relatively simple, inexpensive assessment is necessary. However, these tests all suffer from important limitations, including poor precision. Insulin resistance is increasingly being assessed in clinical situations, where relatively simple markers are required. Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.

Background: An imbalance between zinc and copper metabolism has been reported to predispose to coronary artery disease (CAD) in Western populations, but there are little data for other racial groups. We have therefore investigated the association between serum copper and zinc, and CAD in Iranian subjects undergoing coronary angiography., Methods: Serum copper, zinc, fasting lipid profile, and blood glucose levels were measured in 114 patients (67 male and 47 female) undergoing routine coronary angiogram. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including menopausal status and smoking habit, were assessed by questionnaire., Results: Male patients had lower serum copper (p<0.05), lower serum zinc (p<0.05), and higher serum zinc/copper ratio (p<0.05) than females. Serum copper and zinc concentrations were significantly lower in the subjects with angiographically defined CAD than those patients with a normal angiogram, although the zinc/copper ratio was higher in these patients (p<0.001). Serum copper (r=-0.303, p<0.001) and zinc (r=-0.250, p<0.01) concentrations were both inversely related to age, and copper was positively associated with fasting serum triglycerides (r=0.188, p<0.05)., Conclusion: Serum copper and zinc concentrations were significantly lower in Iranian patients with abnormal versus those with a normal angiogram. However, the zinc/copper ratio was higher in patients with CAD compared to subjects without CAD. Serum zinc and copper concentrations appear to be influenced by several physiological factors including age and gender.

Introduction: Several cross-sectional and cohort studies have reported an association between serum markers of inflammation such as C-reactive protein, and coronary heart disease in Caucasian populations. We aimed to investigate the relationship between levels of serum C-reactive protein (hs-CRP) and the presence of coronary artery disease (CAD) in Iranian patients undergoing coronary angiography., Methods: Serum hs-CRP, fasting lipid profile and blood glucose levels were measured in 110 patients (61 males and 49 females) undergoing routine coronary angiography. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including post-menopausal status and smoking habit were assessed by questionnaire., Results: Of the 110 subjects undergoing angiography, 74 (67.28%) had significant CAD (CAD+) and 36 (32.72%) were classified as having insignificant CAD (CAD-). Mean age (p<0.01), waist circumference (p<0.01) and LDL (p<0.05) and median values of hs-CRP (p<0.01) and triglycerides (p<0.05) were higher in the patients CAD+ than in the subjects CAD-. The proportion of women who were postmenopausal was also significantly higher in the CAD+ group. Age (p<0.01), waist circumference (p<0.05) and hs-CRP (p<0.05) were significant CAD predictive factors from logistic regression analysis. Serum hs-CRP concentrations were significantly higher in smokers compared to non-smokers (p<0.05), low density lipoprotein (LDL) (r=0.31, p<0.001), and serum triglycerides (r=0.191, p<0.05) correlated with serum hs-CRP. The median value of serum hs-CRP increased with the severity of the disease, but failed to reach statistical significance., Conclusion: Serum hs-CRP is an independent predictor of angiographically defined CAD in an Iranian population. Measurement of the serum hs-CRP level may improve risk stratification among patients suspected of having CAD. The strong correlations between serum hs-CRP with LDL and smoking may be due to the putative pro-inflammatory effects of these two parameters. The association with serum triglycerides may be indirect and related to insulin resistance and adiposity.

There have been inconsistent reports on the relationship between iron status and coronary artery diseases (CAD), and little data on this relationship in non-Caucasian populations. We assessed dietary iron by questionnaire and measured serum iron and ferritin levels in 270 Saudi male subjects without established CAD, 130 of whom were angiogram negative. Serum lipid profile, glucose, high sensitivity-C reactive protein (hs-CRP), serum soluble intercellular adhesion molecules-1 (sICAM-1), and caeruloplasmin were measured in all subjects. The angiogram negative patients, had lower serum ferritin (p<0.05) and iron (p<0.0001) levels than the 140 subjects without reported cardiovascular diseases (CVD). Serum iron correlated with serum triglycerides (p<0.0001) and total cholesterol (p<0.05) levels for this latter group and the groups combined. Serum ferritin correlated with serum total cholesterol and low-density lipoprotein (LDL)-cholesterol in the combined group (p<0.05), and was correlated with blood glucose and serum LDL-cholesterol (p<0.05) in the subjects without reported CVD. After adjustment for confounding variables, serum iron levels remained a significant correlate with total calorie intake and serum triglycerides. Serum ferritin also correlated significantly with cholesterol intake and fasting serum total cholesterol. Dietary iron was significantly related to dietary cholesterol and fiber, age, smoking habits, and serum total cholesterol level. Hence, indices of iron status were related to several coronary risk factors in the Saudi population.

Objective: The present study was undertaken to investigate the possible existence of an endogenously generated circadian rhythm in endothelial function in women and whether this rhythm is altered after the menopause., Methods: Healthy non smoking women (11 pre-menopausal and 13 postmenopausal women) were studied during a 22 h period under constant routine conditions; endothelium-dependent (flow-mediated dilation (%FMD)) and -independent (glyceryl-trintrate (GTN)-mediated) function was assessed every 2 and 4 h, respectively, by high-resolution ultrasound of the brachial artery., Results: %FMD and %GTN was significantly higher in pre-menopausal women (9.9+/-1.0%FMD (mean+/-S.E.M.); 18.2+/-1.8%GTN; P<0.01) compared with postmenopausal women (6.5+/-0.5%FMD; 11.5+/-1.6%GTN). A significant day-night variation in %FMD was observed pre-menopausal women (day 9.2+/-0.8%; night 10.4+/-1%; P<0.05) with an attenuated rhythm in postmenopausal women (day 6.8+/-0.6%; night 6.0+/-0.4%)., Conclusions: The findings show a circadian rhythm in %FMD in pre-menopausal women, which disappears after the menopause. The reduction in %FMD and an absence of a day-night variation in %FMD in postmenopausal women may have important implications for the incidence of coronary heart disease in women after the menopause.

The epidermal growth factor receptor is a member of type-I growth factor receptor family with tyrosine kinase activity that is activated following the binding of multiple cognate ligands. Several members of the EGF family of ligands are expressed by cells involved in atherogenesis. EGF receptor mediated processes have been well characterised within epithelial, smooth muscle and tumour cell lines in vitro, and the EGF receptor has been identified immunocytochemically on intimal smooth muscle cells within atherosclerotic plaques. There is also limited evidence for the expression of the EGF receptor family on leukocytes, although their function has yet to be clarified. In this review, we will discuss the biological functions of this receptor and its ligands and their potential to modulate the function of cells involved in the atherosclerotic process.

Background: The relationship between coronary risk score (CRS), individual coronary risk factors and the serum inflammatory markers, high sensitivity C-reactive protein (hsCRP), ceruloplasmin (Cp), and soluble intercellular adhesion molecule-1 (sICAM-1) was studied in 140 Saudi males without clinically evident coronary heart disease (CHD)., Methods: One hundred forty subjects without clinically evident CHD were categorized into age tertiles. Demographic data together with an estimate of CRS using Framingham and PROCAM algorithms were obtained, and serum lipid profile, glucose, hsCRP, sICAM-1, and Cp were measured. Macronutrient intake was assessed by a questionnaire. The relationship between CRS, biochemical markers and diet was assessed by univariate and multivariate analysis., Results: There was no significant difference in median hsCRP, sICAM-1 or Cp between the age groups. Serum Cp was positively associated with age (r=0.224, p<0.01) and FRS score (r=0.174, p<0.05). Serum sICAM-1 was negatively associated with PROCAM score (r=-0.183, p<0.05). sICAM-1 was positively associated with HDL cholesterol (r=0.36, p<0.0001) among non-diabetics and negatively associated (r=-0.397, p<0.05) among diabetic subjects. Age and dietary intake of saturated fatty acids together explained 7.9% of the variation in serum Cp level in a stepwise multiple regression model. Similarly 6.5% of the variation in serum sICAM-1 level was explained by the total cholesterol/HDL-C ratio. The youngest tertile of the group (<30 y) had the highest dietary intake of energy, fat and saturated fatty acids (p<0.05), and also had a high prevalence of obesity, smoking and sedentary lifestyle., Conclusion: We have demonstrated that there is a high prevalence of coronary risk factors and poor dietary intake within a Saudi male population, and that dietary factors are associated with serum sICAM-1 and ceruloplasmin but not hsCRP concentrations in this group.

Background: Traditional coronary risk factors do not fully explain variations in the incidence of cardiovascular disease (CVD). Epidemiological studies have implicated perturbations in selenium, copper, and zinc metabolism in the aetiology of CVD. However, these studies have been principally undertaken in Caucasian populations, in whom trace element intake is generally sufficient., Method: We have measured serum and urine selenium, copper, and zinc; and superoxide dismutase, glutathione peroxidase, and lipid peroxide concentrations in 130 Saudi male subjects with established CVD, and 130 age-matched controls., Results: Diabetes mellitus, positive smoking habit (p<0.0001 for both), and hypertension (p<0.05) were more prevalent among CVD patients. Urinary copper (p<0.0001) and zinc (p<0.05) were higher among controls. Serum selenium concentrations were lower among CVD patients (p<0.001), and a high proportion (52%) had selenium levels below 79mug/L compared to controls (22%) (p<0.0001). Conditional logistic regression analysis, showed the characteristics differentiating CVD patients from controls were serum zinc (odds ratio (OR) 0.92, confidence interval (CI) 0.85-0.99, p<0.05), serum copper/zinc ratio (OR 0.31, CI 0.10-0.96), serum selenium (OR 0.07, CI 0.02-0.31, p<0.0001), and urine selenium (OR 3.34, CI 1.40-7.99, p<0.01)., Conclusion: Measures of trace metals status appear to be associated with the risk of atherosclerosis in a Saudi male population.

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.

Traditional risk factors do not appear to explain fully the variation in the incidence of the cardiovascular diseases (CVD). Epidemiological studies have not been entirely consistent with regard to the relationship between antioxidant vitamin intake and CVD and there appears to be little data on this relationship in non-Caucasian populations. This study aimed to investigate the dietary intake of vitamin A, C, and vitamin E, and carotenoids, serum concentrations of vitamin E and A and indices of lipid peroxidation were measured in male Saudi patients with established CVD and age-matched controls. We assessed the dietary intakes of vitamins A, C, and E and carotenoids, by a food frequency questionnaire. Serum vitamins A and E concentrations were measured by HPLC, in 130 Saudi male subjects with established CVD, and 130 age-matched controls. We also determined serum lipid profiles (total cholesterol, triglycerides, HDL-C, LDL-C), lipoprotein (a), oxidized LDL, and serum lipid peroxide concentrations. Diabetes mellitus (P<0.0001), a positive smoking habit (P<0.0001) and hypertension (P<0.05) were more prevalent among CVD patients. Levels of dietary vitamin E and A were also significantly higher among cases. In conditional logistic regression analysis, the most significant characteristics differentiating CVD patients from controls were diabetes mellitus (Odds ratio 2.49, CI 1.42-4.37, P<0.001), total fat intake (Odds ratio 1.02, CI 1.01-1.03, P<0.01), serum vitamin A (Odds ratio 0.72, CI 0.53-0.99, P<0.05), and the vitamin A/total fat intake ratio (Odds ratio 1.04, CI 1.01-1.06, P<0.01). In a Saudi population, smoking habit and hypertension were significantly more common among patients with CVD. Multivariate analysis showed that dietary total fat and vitamin A and the presence of diabetes mellitus were independent coronary risk factors. This is the first report of a potentially deleterious effect of dietary vitamin A in a non-Caucasian population. However it is possible that unidentified residual confounding factors may account for this finding.

Patients previously not treated with a lipid-lowering agent (n = 20; mean age 49.15 +/- 3.28 years) were treated with either 10 mg/day of Simvastatin (n = 11), or Atorvastatin (n = 9) for 4 months. Fourteen additional patients were recruited from the same clinic at the same hospital as a control group. The medication of these latter patients was unaltered for 4 months and the same parameters were measured as for the statin groups. Serum concentrations of zinc, copper, caeruloplasmin, selenium, glutathione peroxidase (GPx) and C-reactive protein (CRP) were measured together with their lipid profiles pre- and post-treatment. In addition to reducing serum total and low-density lipoprotein (LDL) cholesterol (p < 0.0001), statin treatment was associated with a significant reduction in mean serum zinc (9%, p = 0.03), copper (9%, p < 0.01), caeruloplasmin (24%, p < 0.05), and median CRP (45%, p < 0.03). Similar changes were not observed in the control patients. No significant effects were observed for serum selenium, copper/caeruloplasmin ratio, or GPx (p > 0.05) in either statin or control groups. These changes may be related to the known anti-inflammatory properties of the statin class of drugs.

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination.

The recruitment of peripheral monocytes to the sub-endothelial space, their development into macrophages and subsequent proliferation are critical events during atherosclerosis. Receptors for epidermal growth factor (EGF) have been identified on cells of the myeloid lineage, but a role for them in atherogenesis has yet to be described. We have identified functional EGF receptors (EGFR, ErbB1/HER-1) on peripheral blood monocytes and monocyte-derived macrophages. Uniquely, these receptors were found to mediate both chemotaxis in monocytes and macrophages and proliferation in macrophages. EGFR mRNA was detected in atherosclerotic plaques, but not in morphologically normal aortae and EGFR receptor staining co-localised with macrophage staining in these plaques. The identification of receptors for EGF on peripheral blood monocytes, macrophages and atherosclerotic lesions, together with their transduction of two functionally important cellular events, heightens the potential importance of members of the EGF super-family in atherogenesis and other chronic inflammatory processes.

We describe the case of a 69-year-old man with a history of muscular symptoms dating back to his childhood; McArdle's disease (glycogen-storage disease V) was diagnosed following an episode of myositis in which a statin and physical exertion appear to have been precipitating factors. This case demonstrates that the ischaemic lactate-ammonia test still has a place in screening patients with symptoms suggestive of McArdle's disease and emphasizes the importance of carrying out glycogen phosphorylase histochemistry on the skeletal muscle biopsy to confirm the diagnosis. In patients who develop a raised plasma creatine kinase level or muscular symptoms during lipid-lowering therapy, the clinician should be alert to the possibility of an underlying myopathy.

The regional accumulation of aluminium in the brain of male albino Wistar rats was investigated following 4 weeks of administration by intraperitoneal injection of aluminium lactate (10mg aluminium/kg body weight). The consequences of concomitant dietary vitamin E (5, 15, or 20 mg vitamin E/g of food) were also studied. Rat brains were dissected into functional regions, for the measurement of aluminium and markers of oxidative stress. Plasma aluminium levels were increased in all groups of animals receiving aluminium lactate (p < 0.01), and these levels were significantly reduced in rats receiving concomitant vitamin E (p < 0.05). In the group of rats receiving aluminium alone, levels of brain tissue aluminium were increased in all regions of brain examined (p< 0.01). Brain tissue aluminium levels were reduced by concomitant dietary vitamin E. Catalase and reduced glutathione levels were both reduced in several regions of brain in animals treated with aluminium (p < 0.05). Aluminium treatment was not associated with a significant increase in reactive oxygen species (ROS) generation (p > 0.05), although ROS production was attenuated by dietary vitamin E (p < 0.05) in some regions.