The Wretched of the Earth

Rationale:MicroRNAs (miRNAs) have been implicated in the epigenetic regulation of key metabolic, inflammatory, and antiangiogenic pathways in type 2 diabetes (DM) and may contribute to common disease complications. Objective:In this study, we explore plasma miRNA profiles in patients with DM. Methods and Results:Total RNA was extracted from plasma samples of the prospective population-based Bruneck study. A total of 13 candidate miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls (1995 evaluation, n=80 each). Quantitative PCR assessment revealed lower plasma levels of miR-20b, miR-21, miR-24, miR-15a, miR-126, miR-191, miR-197, miR-223, miR-320, and miR-486 in prevalent DM, but a modest increase of miR-28-3p. Findings emerged as robust in multivariable analysis and were independent of the standardization procedure applied. For endothelial miR-126, results were confirmed in ...

Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes

Nationalist Thought and the Colonial World: A Derivative Discourse?

Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics.

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart.

Endothelial progenitor cell (EPC) cultures and colony-forming units (CFUs) have been extensively studied for their therapeutic and diagnostic potential. Recent data suggest a role for EPCs in the release of proangiogenic factors. To identify factors secreted by EPCs, conditioned medium from EPC cultures and CFUs was analyzed using a matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer combined with offline peptide separation by nanoflow liquid chromatography. Results were verified by RT-PCR and multiplex cytokine assays and complemented by a cellular proteomic analysis of cultured EPCs and CFUs using difference in-gel electrophoresis. This extensive proteomic analysis revealed the presence of the proangiogenic factor thymidine phosphorylase (TP). Functional experiments demonstrated that inhibition of TP by 5-bromo-6-amino-uracil or gene silencing resulted in a significant increase in basal and oxidative stress-induced apoptosis, whereas supplementation with 2-deoxy-d-ribose-1-phosphate (dRP), the enzymatic product of TP, abrogated this effect. Moreover, dRP produced in EPC cultures stimulated endothelial cell migration in a paracrine manner, as demonstrated by gene-silencing experiments in transmigration and wound repair assays. RGD peptides and inhibitory antibodies to integrin αvβ3 attenuated the effect of conditioned medium from EPC cultures on endothelial migration. Finally, the effect of TP on angiogenesis was investigated by implantation of Matrigel plugs in mice. In these in vivo experiments, dRP strongly promoted neovascularization. Our data support the concept that EPCs exert their proangiogenic activity in a paracrine manner and demonstrate a key role of TP activity in their survival and proangiogenic potential.

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Proteomics Identifies Thymidine Phosphorylase As a Key Regulator of the Angiogenic Potential of Colony-Forming Units and Endothelial Progenitor Cell Cultures

This article challenges existing analyses of state failure and their casting of African societies in the role of deviant Other to those of Western Europe and North America Drawing on insights derived from postcolonial studies, the article argues that the comparative approach to identifying so‐called failed states adopted by this literature contrasts African states to a static, ahistorical definition of the state based on exclusively European values customs, practices, organisation and structures In this way, failed state analysts constitute the identities of African societies in relation to those of the West, simultaneously attributing negative characteristics to the former and positive to the latter By calling for a rejection the term failed state the article seeks to challenge the continued positioning of African societies in the role of delinquent, deviant and imperfect Other

Beyond the Other? A postcolonial critique of the failed state thesis

The epidemic of heart failure due to coronary artery disease is a leading cause of morbidity and mortality worldwide. The hallmark of this pathology is maladaptive ventricular remodelling that precipitates contractile dysfunction, and ultimately leads to the overt syndrome of congestive heart failure. The central feature in this malignant cascade is the massive loss of cardiomyocytes, followed by replacement with fibrotic scar; this ultimately leads to organ failure which is further accelerated by haemodynamic overload, inflammatory–oxidative stress, and/or impaired vascularisation. Despite continuous advances in disease management, the available medical, interventional or surgical treatments fall short of addressing the root cause of disease and are typically limited to palliative strategies mitigating disease symptomatology.

The rationale for stem cell based regenerative medicine applied to the treatment of heart diseases is based on the realisation that natural self renewing processes innate to the myocardium, while sufficient to sustain normal homeostasis, fall short of salvaging heart muscle following massive injury—as in the setting of myocardial infarction.1 Accordingly, boosting the cardiac reparative capacity through supplementation of stem cell pools has been increasingly considered as a novel therapeutic approach. Indeed, it is now recognised that extracardiac (eg, bone marrow) in addition to intracardiac progenitor cells are mobilised and home to the site of the myocardial injury to participate in the compensatory healing response.1 w1 Furthermore, there is growing evidence that such cells participate in the maturation and induction of collateral vascular growth and neovasculogenesis, and may acquire phenotypic properties of neighbouring cardiac myocytes.1 These findings, propelled by recent progress in developmental biology, offer an unprecedented opportunity to achieve repair of damaged myocardium using stem cells as new therapeutic tools. Here, we focus on the current clinical experience as well needs for successful translation of the emergent field of cell based therapy from proof-of-concept …

https://heart.bmj.com/content/heartjnl/96/10/792.full.pdf

Cells as biologics for cardiac repair in ischaemic heart failure

Objectives The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes. Background CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell–capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed. Methods In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis. Results The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level–based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models–adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days. Conclusions The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.

The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody–Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis

Political Topographies of the African State: Territorial authority and institutional choice, by Catherine Boone. Cambridge: Cambridge University Press, 2003. xiii + 407 pp. £19.99 paperback. ISBN 0521532647 (paperback).

Jonathan Hill

Papers

Proteomics Identifies Thymidine Phosphorylase As a Key Regulator of the Angiogenic Potential of Colony-Forming Units and Endothelial Progenitor Cell Cultures

Beyond the Other? A postcolonial critique of the failed state thesis

Cells as biologics for cardiac repair in ischaemic heart failure

The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody–Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis

Political Topographies of the African State: Territorial authority and institutional choice, by Catherine Boone. Cambridge: Cambridge University Press, 2003. xiii + 407 pp. £19.99 paperback. ISBN 0521532647 (paperback).