Association between dairy intake,lipids and vascular structure and function in diabetes

AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure and function.METHODS A 12-mo randomised controlled trial was conducted to determine the effect of increased consumption of fruit, vegetables and dairy, compared to usual diet, on measures of vascular structure and function in adults with type 1 and type 2 diabetes(n = 108). Thispaper comprises post-hoc analyses investigating the relationship between dairy intake, serum lipid species and vascular health. Central and peripheral blood pressure, carotid femoral pulse wave velocity, augmentation index, serum lipid species and dietary intake were measured at baseline and 3-mo. Common carotid artery intima media thickness was measured at baseline and 12-mo.RESULTS Serum lipid species [lysophosphatidylcholine(LPC) 14:0, LPC 15:0, LPC 16:1, phosphatidylcholine(PC) 29:0 PC 30:0, PC 31:0 and cholesterol ester(CE) 14:0] were associated with the change in full fat dairy consumption(rho 0.19-0.25; P < 0.05). The 3-mo change in some lipids was positively associated with the 3-mo change in central systolic [LPC 14:0(rho 0.30; P = 0.007), PC 30:0(rho 0.28; P = 0.010)] and diastolic blood pressure [LPC 14:0(rho 0.32; P = 0.004), LPC 15:0(rho 0.23; P = 0.04), LPC 16:1(rho 0.23; P = 0.035), PC 29:0(rho 0.28; P = 0.01), PC 30:0(rho 0.36; P = 0.001), PC 31:0(rho 0.30; P = 0.007)] and 12-mo change in common carotid artery intimal medial thickness [CE 14:0(rho 0.22; P = 0.02)]. Pulse wave velocity and augmentation index were unrelated to dairy and lipid species.CONCLUSION An increase in dairy associated lipids appears to be associated with an increase in blood pressure and common carotid intimal medial thickness.

Clinical and dietary predictors of common carotid artery intima media thickness in a population with type 1 and type 2 diabetes: A cross-sectional study

AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness(CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1(n = 23) and type 2 diabetes(n = 127) had mean and mean maximum CCA IMT measured using B mode ultrasound. Dietary intake was measured using a food frequency questionnaire. Clinical and dietary predictors of mean and mean maximum CCA IMT were determined using linear regression analysis adjusted for potential confounders. RESULTS The main predictors of mean and mean maximum CCA IMT were age and weight. After multivariate adjustment there were no dietary predictors of CCA IMT. However,in subjects that were not prescribed a lipid lowering medication alcohol consumption was positively associated with CCA IMT after multivariate adjustment. No difference existed in CCA IMT between subjects with type 1 or type 2 diabetes once age was adjusted for. CONCLUSION CCA IMT was predominantly predicted by age and weight in these subjects with diabetes. The finding that CCA IMT was not different between people with type 1 and type 2 diabetes warrants further investigation in a larger cohort.

Trends in use and costs of prescription medication in patients with type 1 diabetes: 9-year follow-up after kidney transplantation

Aims: Weestimated long-term trends in prescription medication utilization and costs in patients with type 1 diabetes in two different transplant cohorts (Group 1: transplantation 1986-1999,n = 180;Group 2: transplantation 2000-2008, n = 150). Methods: Data obtained from the Finnish Diabetic Nephropathy Study were linked with the Drug Prescription Register (purchases of medications 1995-2009). Generalized linear mixed models under gamma distribution were used to evaluate the medication costs. Results: The total costs of medication decreased (Group 1 from€11,290 to €8760;Group 2 from €12,800 to €9790)during the follow-up (P< 0.0001). The sametrend was observed for immunosuppressive drugcosts (P< 0.0001). Although the cost profiles were similar for the groups (P= 0.9), the cost level in Group 2 was higher than in Group 1 (P< 0.0001). In Group 1 the most common immunosuppressive combination was cyclosporine, azathioprine and corticosteroid, while cyclosporine, mycophenolate mofetil (MMF) with/without corticosteroid was the most common in Group 2. The estimated average costs of cyclosporine in combination withMMFwere 84% (€4130) higher than with azathioprine. Conclusions: Since diabetes or other drugs had only marginal impact on the total costs, the decreasing trend wasmainly due to the costs of immunosuppressants.This finding is consistent with the recent guidelines which recommend reducing doses of immunosuppressants over time to minimize sideeffects.The cost levels differed depending on the combinations of immunosuppressive drugs in use. Those who had MMF in the regimen generated higher costs.

Blood pressure,prevalence of hypertension and hypertension related complications in Nigerian Africans:A review

To review studies on hypertension in Nigeria over the past five decades in terms of prevalence,awareness and treatment and complications.Following our search on Pubmed,African Journals Online and the World Health Organization Global cardiovascular infobase,1060 related references were identified out of which 43 were found to be relevant for this review.The overall prevalence of hypertension in Nigeria ranges from 8%-46.4% depending on the study target population,type of measurement and cut-off value used for defining hypertension.The prevalence is similar in men and women(7.9%-50.2% vs 3.5%-68.8%,respectively) and in the urban(8.1%-42.0%) and rural setting(13.5%-46.4%).The pooled prevalence increased from 8.6% from the only study during the period from 1970-1979 to 22.5%(2000-2011).Awareness,treatment and control of hypertension were generally low with attendant high burden of hypertension related complications.In order to improve outcomes of cardiovascular disease in Africans,public health education to improve awareness of hypertension is required.Further epidemiological studies on hypertension are required to adequately understand and characterize the impact of hypertension in society.

Standardizing a simpler, more sensitive and accurate tail bleeding assay in mice

AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2 Y receptor inhibitor prasugrel at various doses or in mice deficient of Fc Rγ, a signaling protein of the glycoprotein VI receptor.RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleedingpattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels(r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet's haemostatic activity(P < 0.01). Similarly, in mice with genetic disruption of Fc Rγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time.CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited.

Echocardiographic Measures of Strain and Prognosis

Echocardiography is the most frequently used imaging modality to determine cardiac function.Left ventricular ejection fraction the most widely used parameter for evaluation of systolic function,provides important prognostic value in clinical practice,and forms part of the evidence base for many decisions about cardiovascular care.However,ejection fraction has several substantial limitations and is insensitive to subtle changes in systolic function.The assessment of myocardial deformation with echocardiography has been studied for two decades,and is increasingly used in the clinical setting.This technique can precisely characterize the mechanics of myocardial contraction and relaxation.The most commonly used parameter is global longitudinal strain,which is more sensitive than ejection fraction for the measurement of systolic function.This review focuses on the prognostic value of global longitudinal strain in predicting adverse outcomes in cardiovascular disease.

Functional heterogeneity of high density lipoproteins and its future therapeutic indication

The atheroprotective effect of HDL is well-established, the implication being that the higher the plasma levels of HDL,the bigger the benefit to all individuals.Such a supposition has led to the development of "HDL therapy".It has fast become apparent however that assuming therapeutic benefits by merely raising HDL levels is highly simplistic.The most established atheroprotective function of HDL is its role in reverse cholesterol transport(RCT). However other functions of HDL not directly related to RCT may also contribute significantly to its atheioprotective properties.As well,there are many examples where the functionality of HDL changes discordantly to its concentration such that high levels of HDL can be pro-rather than antiatherogenic under certain metabolic conditions.In humans,the ability of HDL to support cholesterol efflux and maintain endothelial function,or antioxidant function can be diminished despite higher HDL levels.Conversely, apoA-IMilano mutation leads to lower HDL levels,but enhances HDL functionality.We and others have recently shown that HDL also has potent anti-inflammatory actions and can also influence the immune system.The inference of these findings are that first,changes in RCT and HDL functionality are as important,if not more so,than its changes in concentration,and second,that these changes are independent of each other.Thus,"HDL therapy" must consider alterations in RCT and HDL functionality as a result of the treatment and the implications that these changes have on the overall atheroprotective effect of the treatment.

Considerations when using the activPAL monitor in field-based research with adult populations

Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior(and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activP AL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activP AL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activP AL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activP AL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.

HMGB1 induces secretion of matrix vesicles which participate in microcalcification of atherosclerotic plaques

AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditions. Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles( MVs) from macrophages. METHODS: HMGB1 was added to the medium of macrophages,the secretion of MVs in the supernatant was tested by flow cytometry analysis. The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining. Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs. Then we subcutaneous injection into mice with MVs to induce regional mineralization. RESULTS: HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis. TNAP activity,considered as a marker of MVs maturation,was higher in HMGB1-induced MVs compared to the control-MVs. HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase 2( n SMase2) that involved the receptor for advanced glycation end products( RAGE) and p38MAPK( upstream of n SMase2). Inhibition of n SMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part,via the RAGE / p38 MAPK /n SMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 may participated in the early calcification of atherosclerotic plaques.

Epithelial-mesenchymal Plasticity in Breast Cancer Metastasis

Transitions between epithelial and mesenchymal states, which we have termed Epithelial Mesenchymal Plasticity (EMP), are

Risk stratification for coronary artery disease in multi-ethnic populations:Are there broader considerations for cost efficiency?

Coronary artery disease(CAD) screening and diagnosis are core cardiac specialty services.From symptoms,autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies.While angina remains a clinical diagnosis,most cases require correlation with a diagnostic modality.At the onset of the evidence building process much research,now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available.Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived.While it would seem veryunlikely that for the majority,scientific arguments against guidelines would differ,however from a translational perspective,there will be populations who differ and importantly there are cost-efficacy questions,e.g.,the most suitable first-line tests or what parameters equate to an adequate test.This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

Temporal changes in circulating P-selectin,plasminogen activator inhibitor-1,magnesium,and creatine kinase after percutaneous coronary intervention

Objective:This study aims to determine the mechanisms underlying restenosis and ischemia-reperfusion injury of the myocardium after percutaneous coronary intervention(PCI).Methods:The present study examined serial changes(5 min,30 min,2 h,6 h,and 24 h after PCI) in circulating P-selectin,plasminogen activator inhibitor-1(PAI-1),magnesium(Mg),and creatine kinase-myocardial band fraction(CK-MB) levels,which may be associated with restenosis and myocardial injury in patients undergoing PCI.The occurrence rates of major adverse cardiovascular events were collected over a six-month follow-up.Results:PCI induced an early elevation of P-selectin,which correlated positively with the inflation pressure used in the PCI procedure.PCI also caused a significant and sustained decrease in serum Mg in PCI patients,without an effect on PAI-1.An increase in CK-MB was observed in PCI patients,although values were within normal reference range.In addition,elevated P-selectin and decreased Mg measured shortly after the coronary angioplasty procedure were associated with recurrent treatment and heart failure,respectively.Conclusions:Our study demonstrates that PCI induces temporal changes of P-selectin,Mg,and CK-MB,which may be involved in restenosis and ischemia-reperfusion injury.These findings highlight the need for using antiplatelet therapy and Mg to reduce the risks associated with PCI.

控制不良2型糖尿病患者的营养问题 需要没有专业人员参与的长时间干预

在一项随机对照试验（见本期第303页）中，Coppell和他的同事们评估了强化饮食干预对优化药物治疗但仍高血糖的2型糖尿患者血糖控制和心血管疾病风险因素的影响。作者发现接受个体化饮食指导患者的糖化血红蛋白（HbA1c）（-0．4％，95％可信区间0．7％～0．1％）、体重指数和腰围明显改善。

Immune regulation by CD52-expressing CD4 T cells

T-cell regulation by CD52-expressing CD4 T cells appears to operate by two different and possibly synergistic mechanisms. The first is by its release from the cell surface of CD4 T cells that express high levels of CD52 that then binds to the inhibitory sialic acid-binding immunoglobulin-like lectins-lO （Siglec-lO） receptor to attenuate effector T-cell activation by impairing phosphorylation of T-cell receptor associated Ick and zap-70. The second mechanism appears to be by crosslinkage of the CD52 molecules by an as yet unidentified endogenous ligand that is mimicked by a bivalent anti-CD52 antibody that results in their expansion.

Device-Based Treatment in Hypertension:At the Forefront of Renal Denervation

Percutaneous renal denervation is a novel device therapy that modifies the circulatory regulatory system and has received considerable attention recently.This treatment partially blocks the renal sympathetic nervous system,which is an organ-connecting pathway between the brain and the kidney.Denervation techniques currently under clinical investigation include radiofrequency,ultrasonic,and chemical ablation with alcohol,all of which are executed through transcatheter access to the renal artery.All recently published randomized sham-controlled trials have shown a clear antihypertensive effect of renal denervation over 24 hours,including during the nighttime and early morning.This treatment has promise in the management of poorly controlled hypertension as well as in the prevention of the development or aggravation of arrhythmias and heart failure.