The association of biomarkers with pain and function in acute and subacute low back pain: a secondary analysis of an RCT.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal condition and a major cause of disability worldwide. Previous studies have found associations of biomarkers with pain and pain-related disability in LBP patients. This study aimed to explore the association between serum biomarkers and pain and disability in patients with acute or subacute axial LBP. METHODS: This study was ancillary to a parent randomized controlled trial. Enrolled participants were randomized into three intervention groups: one of two types of spinal manipulation or medical care. In the parent study, 107 adults who experienced a new episode of LBP within 3 months prior to enrollment were recruited. For this study, 90 of these 107 participants consented to have blood samples obtained, which were drawn immediately before the beginning of treatment. Seven biomarkers were chosen based on previous literature and analyzed. Clinical outcomes were pain and Oswestry Disability Index (ODI) evaluated at baseline and 4 weeks. Spearman's |r| was used to study the association of initial levels of each biomarker with pain and ODI scores at baseline and with changes in outcome scores from baseline to 4 weeks (end of treatment) within each intervention group. RESULTS: At baseline, 4 of 7 biomarkers had an association with pain that was |r| ≥ .20: neuropeptide Y (NPY) (r = 0.23, p = .028), E-Selectin (r = 0.22, p = .043), vitamin D ((r = - 0.32, p = .002), and c-reactive protein (CRP) (r = 0.37, p = .001). No baseline biomarker had an association with disability that was |r| ≥ 0.20. For the correlations of baseline biomarkers with 4-week change in outcomes, vitamin D showed a correlation with change in disability and/or pain (|r| ≥ 0.20, p > .05) in manipulation-related groups, while CRP, NPY, and E-selectin along with TNFα, Substance P and RANTES showed at least one correlation with change in pain or disability (|r| ≥ 0.20, p > .05) in at least one of the treatment groups. CONCLUSIONS: In 90 LBP patients, the analyzed biomarkers, especially vitamin D, represent a small set of potential candidates for further research aimed at individualizing patient care. Overall, the associations investigated in the current study are an initial step in identifying the direct mechanisms of LBP and predicting outcomes of manipulation-related treatments or medical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01211613, Date of Registration: September 29, 2010, https://clinicaltrials.gov/ct2/show/NCT01211613?term=schneider&cond=Low+Back+Pain&cntry=US&state=US%3APA&draw=2&rank=1.

Effect of pomegranate juice on vascular adhesion factors: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases, obesity, and insulin resistance demonstrate elements of functional impairment of the endothelium. Treatment of endothelial dysfunction with natural products, such as pomegranate, can open new ways in the treatment of cardiovascular diseases. PURPOSE: The present meta-analysis provides information in highlighting the role of pomegranate in endothelial dysfunction. METHODS: Various databases, such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were searched up to July 2020 using relevant keywords. We have selected the studies that investigated the effects of pomegranate on vascular adhesion factors, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and interleukin-6 (IL-6). MD with 95% CrI with 100,000 iterations by using Markov chain Monte Carlo code were used. RESULTS: Pooled effect size of articles in human studies indicated that pomegranate juice was not significantly effective on ICAM-1 [MD: -0.42; CrI: (-1.01, 0.17)], VCAM-1 [MD: -0.20; CrI: (-1.95, 1.40)], and E-selectin [MD: -0.21; CrI: (-1.62, 1.21)] compared to the control group. But it can significantly reduce IL-6 [MD: -1.07; CrI: (-1.90, -0.19)]. CONCLUSION: Generally, present study showed that pomegranate juice has no significant effect on vascular adhesion factors, ICAM-1, VCAM-1, and E-selectin, but can reduce IL-6 significantly. Future prospective randomized clinical trials with longer intervention duration are warranted to obtain a precise conclusion.

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

OBJECTIVE: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. PATIENTS AND METHODS: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific ß1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor ß1(TGF-ß1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. RESULTS: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-ß1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-ß1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). CONCLUSIONS: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

The effect of intramuscular megadose of vitamin D injections on E-selectin, CRP and biochemical parameters in vitamin D-deficient patients with type-2 diabetes mellitus: A randomized controlled trial.

BACKGROUND AND AIMS: Inflammatory processes has been shown to be associated with the development of type 2 diabetes mellitus (T2DM) in which vitamin D supplementation might exert beneficial outcomes. We examined the effects of vitamin D supplement on inflammatory and cell adhesion molecule in patients with T2DM. METHODS: This study consisted of 50 patients with T2DM who had vitamin D deficiency. Participants were randomized into two groups of 25 in which the intervention group received two intramuscular injections of a 200000-IU vitamin D supplement, one at week 0 and another at week 4. The concentrations of fasting blood glucose (FBG), lipid profiles, liver enzymes, E-selectin, C-reactive protein (CRP), calcium, phosphorus, serum 25-hydroxyvitamin D [25(OH)D] and anthropometric indices were obtained before and after 8 weeks. RESULTS: Vitamin D resulted in significant reductions in CRP(P = 0.01) and gamma glutamyl transferase (GGT) levels(P = 0.03) and significant increases in 25(OH)D concentrations(P = 0.01) in the intervention group compared with the control. Within-group comparisons showed that FBG decreased significantly in the intervention group(P = 0.04). No significant changes were observed regarding within- and between-group comparisons of the other markers. CONCLUSION: Vitamin D had beneficial effects on the levels of CRP, serum 25(OH)D and GGT among vitamin D deficient patients with T2DM. (http://www.irct.ir: IRCT2017100336539N1).

Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis.

OBJECTIVES: The rationale for the current study was to evaluate the efficacy of flaxseed supplementation on important adhesion molecules and inflammatory cytokines in adults. METHODS: We conducted searches of published literature in PubMed, Scopus, Web of Science, and Google Scholar databases from inception until May 2019. All randomized controlled trials (RCTs) which investigated the effects of flaxseed supplementation on the circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion protein 1 (VCAM-1), E-selectin, and intercellular adhesion molecule 1 (ICAM-1) were included in our analysis. Results were summarized using weighted mean differences (WMDs) by random-effects model. RESULTS: Forty eligible RCTs, including 2520 participants were identified. The results of the meta-analysis revealed flaxseed supplementation reduced the concentrations of CRP (WMD = -0.387 mg/L; 95% CI: -0.653, -0.121, p = 0.004), IL-6 (WMD = -0.154 pg/Ml; 95% CI: -0.299, -0.010, p = 0.036), and VCAM-1 (WMD = -22.809 ng/ml; 95% CI: -41.498, -4.120, p = 0.017) but had no significant effect on TNF-α (WMD = -0.077 pg/mL; 95% CI: -0.317, 0.163, p = 0.530), ICAM-1 (WMD = -8.610 ng/ml; 95% CI: -21.936, 4.716, p = 0.205), and E-selectin (WMD = -1.427 ng/ml; 95% CI: -4.074, 1.22, p = 0.291). CONCLUSIONS: These findings showed that flaxseed supplementation may improve some circulating concentrations of specific adhesion molecules and inflammatory cytokines. However, well-designed trials are needed to confirm the range of non-significant and/or equivocal findings.

Addition of marine omega-3 fatty acids to statins in familial hypercholesterolemia does not affect in vivo or in vitro endothelial function.

BACKGROUND: Prestatin trials reported positive effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular disease, whereas recent studies and meta-analyses have not reproduced these results. The effect of n-3 PUFA in patients with familial hypercholesterolemia (FH), a group with particularly high risk of cardiovascular disease, is not well established. OBJECTIVE: We investigated the effect of n-3 PUFA in the early stage of atherosclerosis in FH patients by evaluating in vivo (peripheral arterial tonometry [PAT]) and in vitro (plasma asymmetric dimethylarginine and E-selectin) endothelial function. METHODS: This was a double-blind, placebo-controlled cross-over study with 34 FH patients on statin treatment (mean age 46.6 years). In random order, all individuals were treated for 3 months with high-dose n-3 PUFA (2 g, ×2) and 3 months placebo (olive oil, 2 g ×2), separated by a 3-month washout period. Anthropometric data, blood samples, and PAT were collected at 4 time points. RESULTS: There were no significant changes in reactive hyperemia index measured by PAT after n-3 PUFA compared with placebo, median reactive hyperemia index after n-3 PUFA was 1.98 and after placebo 1.96 (P = .51). No significant changes were detected in the soluble endothelial marker asymmetric dimethylarginine (in 2 different assays) when comparing n-3 PUFA and placebo (P = .92 and .14, respectively). Finally, the level of E-selectin did not change significantly during the trial (P = .26). CONCLUSION: Addition of n-3 PUFA to standard lipid-lowering treatment in genetically verified FH patients did not affect the in vivo endothelial function or soluble endothelial markers.

Acute heat stress reduces biomarkers of endothelial activation but not macro- or microvascular dysfunction in cervical spinal cord injury.

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b-) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (-93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.

Vitamin D deficiency, endothelial function and bone biomarkers in post-kidney transplantation patients from North India.

PURPOSE: CKD patients after kidney transplantation continue to suffer from elevated CV events which may be related to low vitamin D and its adverse impact on vascular function. The prevalence of vitamin D deficiency in North Indian kidney transplantation patients and its impact on vascular and bone biomarkers is unknown which this study investigated. METHODS: Non-diabetic, stable, > 6 months post-kidney transplantation patients, not on vitamin D supplementation, were recruited after informed consent. Data on demographics, anthropometrics and treatment were collected. Blood samples were stored at - 80 °C until analysis for bone and endothelial cell biomarkers using standard ELISA techniques. RESULTS: The clinical characteristics were: age 37.4 ± 9.9 years, 80% men, 27% ex-smokers, BP 125.5 ± 15.7/78.6 ± 9.7 mmHg, cholesterol 172.0 ± 47.8 mg/dL, hemoglobin 12.6 ± 2.3 g/dL, calcium 9.5 ± 0.6 mg/d and iPTH 58.4 ± 32.9 ng/mL and vitamin D 36.5 ± 39.8 nmol/L. Patients with vitamin D < 37.5 nmol/L (66%) had similar age, serum creatinine, serum phosphate, iPTH, blood pressure but lower calcium (9.3 ± 0.7 vs. 9.6 ± 0.5 mg/dL; p = 0.024), lower FGF23 (median 18.8 vs. 80.0 pg/mL; p = 0.013) and higher E-selectin (15.8 ± 7.9 vs. 13.0 ± 5.5 ng/mL; p = 0.047). On Univariate analysis, E-selectin (r = - 0.292; p = 0.005), FGF23 (r = 0.217; p = 0.036) and calcium (r = 0.238; p = 0.022) were significantly correlated with vitamin D levels. On stepwise multiple regression analysis, only E-selectin was associated with vitamin D levels (ß = - 0.324; p = 0.002). CONCLUSION: Vitamin D deficiency was common in kidney transplant recipients in North India, associated with low FGF23 and high E-selectin. These findings suggest further investigations to assess the role of vitamin D deficiency-associated endothelial dysfunction, its implications and reversibility in kidney transplantation recipients.

Spirulina maxima Decreases Endothelial Damage and Oxidative Stress Indicators in Patients with Systemic Arterial Hypertension: Results from Exploratory Controlled Clinical Trial.

(1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

Effects on oral fat load of a nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols: A randomized, placebo controlled trial.

BACKGROUND: In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking. PURPOSE: We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN: Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day. METHODS: We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load. RESULTS: Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination. CONCLUSIONS: The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.

Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

Background: Vitamin D has been proposed to have anti-inflammatory properties; however, the effect of vitamin D supplementation on inflammation in type 2 diabetes has not been established. Objective: The aim of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on inflammatory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge. Data sources: MEDLINE, CINAHL, Embase, and EBM Reviews were searched systematically from inception to January 25, 2017. Study selection: Randomized controlled trials (RCTs) investigating the effects of vitamin D supplementation (any form, route, and duration, and with any cosupplementation) compared with placebo or usual care on inflammatory markers in patients with type 2 diabetes were selected. Data extraction: Study and sample characteristics and aggregate outcome data were extracted, risk of bias was determined, and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Twenty-eight RCTs were included, 20 of which had data available for pooling. In meta-analyses of 20 RCTs (n = 1270 participants), vitamin D-supplemented groups had lower levels of C-reactive protein (standardized mean difference [SMD] -0.23; 95%CI, -0.37 to -0.09; P = 0.002) and tumor necrosis factor α (SMD -0.49; 95%CI, -0.84 to -0.15; P = 0.005), a lower erythrocyte sedimentation rate (SMD -0.47; 95%CI, -0.89 to -0.05; P = 0.03), and higher levels of leptin (SMD 0.42; 95%CI, 0.04-0.81; P = 0.03) compared with control groups. No differences were observed for adiponectin, interleukin 6, or E-selectin (all P > 0.05). In meta-regression and subgroup analyses, age, sex, body mass index, duration of diabetes, baseline vitamin D status, and dose and duration of supplementation did not alter the results. Conclusions: This meta-analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low-grade inflammation in patients with type 2 diabetes. Systematic Review Registration: PROSPERO CRD42016047755. Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=47755 (9/15/2016).

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease.

PURPOSE: Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients. MATERIALS AND METHODS: Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied. RESULTS: There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (ß = - 0.548, P < 0.001) and lower levels of 25(OH)D (ß = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001). CONCLUSIONS: Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

Xuebijing Injection () increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns.

OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. METHODS: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated. RESULTS: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.

The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial.

PURPOSE: Metabolic syndrome may predispose to cardiovascular diseases. Since, in recent studies, vitamin D is advocated for cardioprotective roles, this study was designed to investigate the effects of vitamin D supplementation on proatherogenic inflammatory markers and common carotid intima media thickness in subjects with metabolic syndrome. METHODS: This randomized double blind clinical trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic syndrome were recruited thorough advertisement and randomized to receive either vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin, and common carotid intima media thickness were measured at the beginning and end of the study. The study was registered at http://www.irct.ir (code: IRCT201409033140N14). RESULTS: Sixteen weeks supplementation with vitamin D increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels (p < 0.001) in the intervention group. There was also a significant difference in parathyroid hormone level at the end of the study (p < 0.001). Vitamin D treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline, vascular cell adhesion molecule-1 and E-selectin levels decreased significantly in vitamin D treated subjects; however, there were no significant differences between two groups. No effect of vitamin D supplementation was observed in either common carotid intima media thickness or high sensitivity C-reactive protein concentrations at the end of the study (p > 0.05). CONCLUSIONS: Vitamin D supplementation improved some proatherogenic inflammatory markers in subjects with metabolic syndrome. No changes of high sensitivity C-reactive protein and carotid intima media thickness were shown after 16 weeks.

Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin.

BACKGROUND AND AIMS: Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of the disease have not been established. The discovery of specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study examines whether the ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1), can reduce atherosclerosis, when administered alone or in combination with a cholesterol-lowering statin. METHODS: ApoE*3Leiden mice were fed a hypercholesterolemic diet for 9 weeks and subsequently treated with RvE1-low (1 mg/kg/day), RvE1-high (5 mg/kg/day), atorvastatin (1.5 mg/kg/day) or the combination of atorvastatin and RvE1-low for the following 16 weeks. RESULTS: RvE1-low and RvE1-high reduced atherosclerotic lesion size to the same extent (-35%; p < 0.05), attenuated the formation of severe lesions, also seen as a proportional increase in the presence of mild lesions, but did not alter plasma cholesterol levels. Cholesterol-lowering atorvastatin reduced atherosclerosis (-27%, p < 0.05), and the combination of RvE1 and atorvastatin further attenuated lesion size (-51%, p < 0.01) and increased the content of mild lesions. RvE1 did not affect plasma SAA, E-selectin, VCAM-1 or MCP-1 but did reduce plasma EPHX4 and down-regulated the local expression of pro-atherogenic genes in the aortae, (e.g. Cd74, Cd44, Ccl2, Ccr5 and Adam17) and significantly inactivated IFN-γ (p < 0.001) and TNF-α (p < 0.001) signalling pathways. CONCLUSIONS: RvE1 attenuates atherogenesis both alone and on top of a statin. The local effects of RvE1 are demonstrated by the modulated aortic expression of genes involved in inflammatory and immune responses, without altering plasma cholesterol or circulating SAA.

Cardio-Metabolic Disease Risks and Their Associations with Circulating 25-Hydroxyvitamin D and Omega-3 Levels in South Asian and White Canadians.

OBJECTIVES: This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada's capital region. METHODS: Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured. RESULTS: SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50-74.9 nmol/L) or optimal (≥ 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA-IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (≥ 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of ≤ 25 kg/m2 were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC. CONCLUSIONS: The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC.

Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.

BACKGROUND: Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was comparing the effect of Cratagol herbal tablet, aerobic exercise and their combination on the serum levels of Intercellular adhesion molecule (ICAM)-1 and E-Selectin in patients with stable angina pectoris. METHODS: Eighty stable angina pectoris patients aged between 45 and 65 years, were randomly divided into four groups including three experimental groups and one control group: aerobic exercise (E), Crataegus oxyacantha extract (S), aerobic exercise and Crataegus oxyacantha extract (S+E), and control (C). Blood sampling was taken 24 h before and after 12 weeks of aerobic exercise and Crataegus oxyacantha extract consumption. The results of serum levels of ICAM-1 and E-selectin were compared. RESULTS: Intergroup comparison of the data revealed a significant reduction (P <0.01) in serum levels of ICAM-1 and E-selectin in experimental groups. Analysis of data showed that the serum levels of ICAM-1 had significant difference when group S+E was compared with groups S and C, but not group E (P = 0.021, P = 0.000 and P = 0.068, respectively). Also the difference between the levels of E-selectin was significant comparing S+E and S but not E with group C (P = 0.021, P = 0.000 and P = 0.052, respectively). CONCLUSIONS: Twelve weeks effects of aerobic exercise and Crataegus oxyacantha extract consuming is an effective complementary strategy to significantly lower the risk of atherosclerosis and heart problems.

Serum lipid profile and inflammatory markers in the aorta of cholesterol-fed rats supplemented with extra virgin olive oil, sunflower oils and oil-products.

Extra virgin olive oil (EVOO) major and minor component anti-inflammatory effect on aorta was evaluated; Wistar rats were fed (9 weeks) on either a high-cholesterol diet (HCD) or a HCD supplemented with oils, i.e. EVOO, sunflower oil (SO), high-oleic sunflower oil (HOSO), or oil-products modified to their phenolic content, i.e. phenolics deprived-EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], HOSO enriched with the EVOO phenolics [HOSO(+)]. HCD induced dyslipidemia and resulted in higher aorta adhesion molecules levels at euthanasia. Groups receiving EVOO, EVOO(-), HOSO, HOSO(+) presented higher serum TC and LDL-c levels compared to cholesterol-fed rats; attenuation of aorta E-selectin levels was also observed. In EVOO/EVOO(-) groups, aorta vascular endothelial adhesion molecule-1 (VCAM-1) was lower compared to HCD animals. SO/SO(+) diets had no effect on endothelial dysfunction amelioration. Overall, our results suggest that major and/or minor EVOO constituents improve aorta E-selectin and VCAM-1, while serum lipids do not benefit.

E-selectin, resistin and reactive oxygen species levels in GnRH -agonist and -antagonist protocols in IVF/ICSI: a prospective cohort study.

PURPOSE: To compare E-selectin, resistin and reactive oxygen species (ROS) levels in serum and follicular fluid (FF) of subfertile women undergoing Controlled Ovarian Hyperstimulation (COH) during IVF/ICSI cycles, using GnRH-agonist and -antagonist protocols. METHODS: In this prospective cohort study, 85 subfertile women undergoing IVF/ICSI were included. Participants underwent the GnRH-agonist and -antagonist protocols; and blood samples were collected at three time points: basic (at start of COH), on the day of hCG and at oocyte retrieval (OR); and from the FF from the first follicle aspirate. Clinical and IVF cycle characteristics, were compared between groups, together with the levels of E-selectin, resistin and ROS in serum and FF, through ELISA. Their prognostic value on pregnancy outcomes was examined. RESULT(S): Examining molecules levels are increasing in serum, from start of COH until OR, irrespectively of the protocol used; FF levels at OR were similar to those in serum at that day. Resistin FF levels were lower in GnRH agonists, compared with the antagonist protocol. Resistin levels at start of COH were associated with clinical pregnancy rates, and this remained significant following adjustment for age, BMI and IVF protocol used, while values of >13.5 ng/ml were associated with a six times greater odd of a pregnancy. CONCLUSION: E-selectin, resistin and ROS levels are increasing during COH, reaching their highest values at OR, with comparable values measured in the FF at that time. Resistin values >13.5 ng/ml are linked with a 6-fold increase on the odds of a pregnancy.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.

BACKGROUND: Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. OBJECTIVE: We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors. DESIGN: In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation. RESULTS: Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. CONCLUSIONS: Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958.