PET Molecular Targets and Near-Infrared Fluorescence Imaging of Atherosclerosis

PURPOSE OF REVIEW: With this review, we aim to summarize the role of positron emission tomography (PET) and near-infrared fluorescence imaging (NIRF) in the detection of atherosclerosis. RECENT FINDINGS: (18)F-FDG is an established measure of increased macrophage activity. However, due to its low specificity, new radiotracers have emerged for more specific detection of vascular inflammation and other high-risk plaque features such as microcalcification and neovascularization. Novel NIRF probes are engineered to sense endothelial damage as an early sign of plaque erosion as well as oxidized low-density lipoprotein (oxLDL) as a prime target for atherosclerosis. Integrated NIRF/OCT (optical coherence tomography) catheters enable to detect stent-associated microthrombi. Novel radiotracers can improve specificity of PET for imaging atherosclerosis. Advanced NIRF probes show promise for future application in human. Intravascular NIRF might play a prominent role in the detection of stent-induced vascular injury

Role of Mesenchymal Stem Cells in Dermal Repair in Burns and Diabetic Wounds

In this review we explore stem cell function in wounds that are resistant to healing, such as burn injuries and diabetic wounds. Diabetic ulcers are of interest due to their remarkable resistance to heal; severe thermal burns are addressed due to critical need for effective therapies for the prevention shock and improvement in scarring. Cell-based therapy utilizing mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, are currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe thermal burns. The clinical utility of stem cells, in particular MSCs, in caring for these types of injuries is primarily based on repairing and replacing cellular substrates, attenuation of inflammation, increasing angiogenesis, and enhancing migration of reparative cells. MSCs are sought after due to their unique ability to initiate different wound-healing programs, depending on the environmental milieu. Thus, this review aims to highlight the properties of MSCs, including their characterization, immunogenicity, and function in the context of dermal repair and regeneration in severe burns and diabetic wounds. Additionally, relevant clinical and pre-clinical studies illustrating the impact of allogeneic and autologous sources of MSCs on therapeutic efficacy are reviewed. Insight into the properties of MSCs and the dramatic host-to-MSC interactions within these pathological states may lead to the development of effective strategies for improving outcomes in impaired wounds

Influencia de la atmósfera de sinterización en la estabilidad térmica de cerámicas de hidroxiapatita reforzadas con zircona

En este trabajo se estudia la influencia de la atmósfera de sinterización sobre la estabilidad térmica de cerámicas de hidroxiapatita (HA) reforzadas con partículas de circona parcialmente estabilizada con magnesia (Mg-PSZ). Los cuerpos verdes fueron obtenidos por prensado uniaxial y las sinterizaciones se realizaron en aire y en oxígeno húmedo. El estudio por difracción de rayos-X y espectroscopía infrarroja permitió comprobar que la atmósfera húmeda evita la descomposición de la hidroxiapatita, todo lo contrario a lo que sucede en aire donde es evidente la presencia del zirconato cálcico (CZ) en la interfaz entre la partícula de circona y la matriz de HA. La caracterización microestructural de los materiales por Microscopía Electrónica de Barrido permitió apreciar el desarrollo de tamaño de grano de los materiales sinterizados. El estudio del comportamiento mecánico mediante ensayos de indentación reveló un aumento de la tenacidad a la fractura en el caso de los materiales que presentaban Mg-PSZ con respecto a la HA pura

354 Clinical Trial of Allogeneic Mesenchymal Stem Cells in Second Degree Burns: Prelim Results

Abstract Introduction Mesenchymal stem cells (MSCs) have been used for many different applications directed at the repair and regeneration of damaged tissue. Previous studies have demonstrated the safety and efficacy of delivering bone marrow cells including MSCs to chronic wounds with substantial improvement in healing. However, information regarding the clinical use of allogenic MSCs in the treatment of burns is relatively unknown. We present the preliminary results of the first human clinical trial evaluating the safety and efficacy of allogeneic MSCs in deep second degree burns. Methods A Phase I/II dose escalation clinical trial evaluating 20 patients with second degree burns at 4 different dose levels ranging from 2,500 to 20,000 cells/ cm2. Wound measurements were taken at time of screening, prior to cell application, and post application until complete wound closure. The wound was traced and measured by digital analytical software. Digital photographs were taken at all time points from initial screening to all subsequent follow up visits. To evaluate safety, blood samples were collected before, during, and after receiving donor MSCs in order to determine their ability to induce an inflammatory cytokine response, using mixed donor MSC/recipient PBMC ELISA assays. Wounds were examined clinically for closure and scarring. Results To date, eleven patients received allogeneic MSC applications on their burn wounds. Of the eleven patients, five have received two administrations of MSCs. ELISA analysis revealed no substantial reaction in cytokine levels of INFγ and TNFα. IL-10 results were varied but no significant increase over baseline cytokine levels. These findings support the immune privileged/immunosuppressive effects of allogeneic MSCs. Wound closure and scarring were felt to be as good or better than expected (clinical and photographic). Conclusions Preliminary results suggest allogeneic MSCs are safe when used on deep second-degree burns. The cytokine analysis demonstrates that MSCs are non-reactive in assays conducted before, during, and after treatment. Larger randomized trials will be required to demonstrate improvements in clinical outcomes. Applicability of Research to Practice This trial supports the promise of stem cell based therapy in the treatment of burn wounds with a favorable safety profile using MSCs

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing

INTRODUCTION: Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. METHODS: In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. RESULTS: Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. CONCLUSIONS: These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process

Advancing Human Rights Policy: Does Grassroots Mobilization and Community Dispute Resolution Matter? Insights from Chiapas, Mexico

This research examines the impact of grassroots organizing at the community level in Chiapas, Mexico, to address problems associated with human rights advocacy and implementation. Traditionally, the nation-state has had the primary responsibility to address issues pertaining to human rights violations and the enforcement of international human rights principles and treaties. Local political struggles and acts of resistance by disenfranchised groups in Mexico offer insight to understand the impact of indigenous and other social movements in furthering human rights. Indigenous populations in the state of Chiapas use local community dispute resolution to contest the inadequacy of the state in responding to the problems that give rise to poverty, lack of human dignity, educational access, racial and ethnic discrimination, lack of political participation in government and the right to equality in economic, social, and political sectors. Drawing from research based on participant observations in Chiapas, Mexico, there is some evidence to suggest that since the 1994 EZLN (Zapatista National Liberation Army) uprising several micro-level political and social movements have contested the power of the state through symbolic and pragmatic organizing efforts. These groups include, but are not limited to, nongovernmental organizations (NGOs), women's groups, and indigenous groups. After the Zapatista uprising, these groups were instrumental in making claims against the state through numerous activities: protests to end the war, the development of NGOs to observe human rights violations, civilian-based Zapatista support groups (base de apoyo), peace camps, and open dialogue with the EZLN. I argue that collective mobilization in local communities serves both symbolic and pragmatic efforts in helping disenfranchised groups empower themselves to address economic, social, and political inequality. Local-level activism has fueled a sense of self-empowerment to change state institutional responses and to involve sectors of civil society domestically and internationally to initiate a proper resolution of issues that are fundamentally related to human rights. Copyright 2005 by The Policy Studies Organization.

Carotid artery ligation induced intimal thickening and proliferation is unaffected by ageing

Following interventions to treat atherosclerosis, such as coronary artery bypass graft surgery, restenosis occurs in approximately 40% of patients. Identification of proteins regulating intimal thickening could represent targets to prevent restenosis. Our group previously demonstrated that in a murine model of vascular occlusion, Wnt4 protein expression and β-catenin signalling was upregulated which promoted vascular smooth muscle cell (VSMC) proliferation and intimal thickening. In this study, the effect of age on VSMC proliferation, intimal hyperplasia and Wnt4 expression was investigated. In vitro proliferation of VSMCs isolated from young (2 month) or old (18–20 month) C57BL6/J mice was assessed by immunocytochemistry for EdU incorporation. As previously reported, 400 ng/mL recombinant Wnt4 protein increased proliferation of VSMCs from young mice. However, this response was absent in VSMCs from old mice. As our group previously reported reduced intimal hyperplasia in Wnt4+/− mice compared to wildtype controls, we hypothesised that impaired Wnt4 signalling with age may result in reduced neointimal formation. To investigate this, carotid artery ligation was performed in young and old mice and neointimal area was assessed 21 days later. Surprisingly, neointimal area and percentage lumen occlusion were not significantly affected by age. Furthermore, neointimal cell density and proliferation were also unchanged. These data suggest that although Wnt4-mediated proliferation was impaired with age in primary VSMCs, carotid artery ligation induced neointimal formation and proliferation were unchanged in old mice. These results imply that Wnt4-mediated proliferation is unaffected by age in vivo, suggesting that therapeutic Wnt4 inhibition could inhibit restenosis in patients of all ages