349 research outputs found
Monocyte-endothelial cell interactions in the regulation of vascular sprouting and liver regeneration in mouse
Background & Aims Regeneration of the hepatic mass is crucial to liver repair. Proliferation of hepatic parenchyma is intimately dependent on angiogenesis and resident macrophage-derived cytokines. However the role of circulating monocyte interactions in vascular and hepatic regeneration is not well-defined. We investigated the role of these interactions in regeneration in the presence and absence of intact monocyte adhesion. Methods Partial hepatectomy was performed in wild-type mice and those lacking the monocyte adhesion molecule CD11b. Vascular architecture, angiogenesis and macrophage location were analyzed in the whole livers using simultaneous angiography and macrophage staining with fluorescent multiphoton microscopy. Monocyte adhesion molecule expression and sprouting-related pathways were evaluated. Results Resident macrophages (Kupffer cells) did not migrate to interact with vessels whereas infiltrating monocytes were found adjacent to sprouting points. Infiltrated monocytes colocalized with Wnt5a, angiopoietin 1 and Notch-1 in contact points and commensurate with phosphorylation and disruption of VE-cadherin. Mice deficient in CD11b showed a severe reduction in angiogenesis, liver mass regeneration and survival following partial hepatectomy, and developed unstable and leaky vessels that eventually produced an aberrant hepatic vascular network and Kupffer cell distribution. Conclusions Direct vascular interactions of infiltrating monocytes are required for an ordered vascular growth and liver regeneration. These outcomes provide insight into hepatic repair and new strategies for hepatic regeneration.National Institutes of Health (U.S.) (Grant R01 GM 49039
Models of Human Vascular Disease: Is There an Animal of La Mancha?
Cervantes understood that models–be they physical or moral lessons–are valid only in as much as they mirror that which they seek to mimic. This is the essential issue presented by Diego et al. in the article published in Revista Española de CardiologĂa. Drug-eluting stents have changed the practice of medicine and are perhaps the most common intervention used today. Millions of stents are placed each year and yet critical questions remain as to whether one design is better than another. The challenge in major part is that, though device designs may be significantly different one from another, detection of a clinical difference is difficult given the rarity of side effects. Human clinical trials are too small and too short to detect differences even in fatal events that occur in 1 in 100 patients per year. The natural fallback is to rely on animal model systems and yet it is unclear how best to use them. Diego et al. describe a study that compares the proliferative response elicited after deployment of paclitaxel-eluting and bare metal stents in porcine coronary arteries. They suggest that the ability of a stent platform to significantly impact late vascular healing depends upon the degree of injury that is created at the time of implantation. Such a result has profound impact on how we consider animal model systems for critical technologies, our view of vascular biology and vascular repair, and our appreciation of the history of work in this field. Moreover, the study shows how a difficult parameter rarely controlled in human interventions–the extent of injury–is such a powerful regulator of clinical effect and restenotic side effect.National Institutes of Health (U.S.) (Grant RO1/GM049039)National Institute of General Medical Sciences (U.S.) (Grant RO1/GM049039
Could antiretrovirals be treating EBV in MS? A case report
We present the case of an HIV-negative patient clinically diagnosed with relapsing-remitting MS who achieved significant disease improvement on Combivir (zidovudine/lamivudine). Within months of treatment, the patient reported complete resolution of previously unremitting fatigue and paresthesiae, with simultaneous improvements in lesion burden detected by MRI. All improvements have been sustained for more than three years. This response may be related to the action of zidovudine as a known inhibitor of EBV lytic DNA replication, suggesting future directions for clinical investigation. Keywords: Multiple sclerosis, Epstein-Barr viru
Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment
Objective: Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. Design: Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. Results: Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. Conclusions: Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation
Video based monitoring of torsional eye movements
Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1979.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING.Bibliography: leaves 177-181.by Elazer Reuven Edelman.M.S
Primary monocytes regulate endothelial cell survival through secretion of Angiopoietin-1 and activation of endothelial Tie2
Objective—Monocyte recruitment and interaction with the endothelium is imperative to vascular recovery. Tie2 plays a key role in endothelial health and vascular remodeling. We studied monocyte-mediated Tie2/angiopoietin signaling following interaction of primary monocytes with endothelial cells and its role in endothelial cell survival.
Methods and Results—The direct interaction of primary monocytes with subconfluent endothelial cells resulted in transient secretion of angiopoietin-1 from monocytes and the activation of endothelial Tie2. This effect was abolished by preactivation of monocytes with tumor necrosis factor-α. Although primary monocytes contained high levels of both angiopoietin 1 and 2, endothelial cells contained primarily angiopoietin 2. Seeding of monocytes on serum-starved endothelial cells reduced caspase-3 activity by 46±5.1%, and 52±5.8% after tumor necrosis factor-α treatment and decreased detected single-stranded DNA levels by 41±4.2% and 40±3.5%, respectively. This protective effect of monocytes on endothelial cells was reversed by Tie2 silencing with specific short interfering RNA. The antiapoptotic effect of monocytes was further supported by the activation of cell survival signaling pathways involving phosphatidylinositol 3-kinase, STAT3, and AKT.
Conclusion—Monocytes and endothelial cells form a unique Tie2/angiopoietin-1 signaling system that affects endothelial cell survival and may play critical a role in vascular remodeling and homeostasis
Garment design and engineering for hospital use
Garments used in hospitals play an important role in user’s comfort and health. This paper presents the developments of a patented design technology for medical garments aimed at users, caregivers, and health care providers. Traditional gowns lacking comfort and protection affect the patient’s dignity. Similarly, patients often use their own garments, which are not designed to provide the best comfort and protection if sensing capacity is affected. Additionally, they can interfere with caregivers’ daily tasks. The proposed pajamas consider these needs and allow an effective interaction between patient and caregiver without compromising the person’s self-esteem. The selection of functional textile fibers and the use of seamless production processes allow the design of products advantageous in the prevention of wounds and pressure ulcers, as pressure points are reduced and the micro-climate of the skin is managed in a more effective way, enhancing the levels of sensorial, physiological and ergonomic comfort.This work is financed by FEDER funds through the Competitive Factors
Operational Program (COMPETE) POCI-01-0145-FEDER-007136 and by national funds
through FCT-Portuguese Foundation for Science and Technology, under the project
UID/CTM/000264 and SFRH/BD/79762/2011.info:eu-repo/semantics/publishedVersio
The Impact of Work Clothing Design on Workers’ Comfort
Physical and physiological comfort, at work and during leisure time, is important to human health and motivation. A growing number of jobs require workers to sit. Most clothes, except those intended for wheelchair users, were designed for walking or the standing position. Clothing designs should be user-oriented and meet users’ needs. Garment design should conform to body position and posture, not just shape and size. In this paper we present the ergometric impact of a new type of trousers designed to adapt to changes in position. Concentrations of compression forces, temperature and pressure were documented in an exploratory pilot study and contrasted to traditional designs. The new trousers showed significant decreases in compression force concentration, especially in and around the knees and waist. Most participants identified comfort as an important factor when purchasing a pair of trousers and that, for working purposes, they would prefer these special trousers rather than traditional designs
Methodological Standardization for the Pre-Clinical Evaluation of Renal Sympathetic Denervation
Transcatheter ablation of renal autonomic nerves is a viable option for the treatment of resistant arterial hypertension; however, structured pre-clinical evaluation with standardization of analytical procedures remains a clear gap in this field. Here we discuss the topics relevant to the pre-clinical model for the evaluation of renal denervation (RDN) devices and report methodologies and criteria toward standardization of the safety and efficacy assessment, including histopathological evaluations of the renal artery, periarterial nerves, and associated periadventitial tissues. The pre-clinical swine renal artery model can be used effectively to assess both the safety and efficacy of RDN technologies. Assessment of the efficacy of RDN modalities primarily focuses on the determination of the depth of penetration of treatment-related injury (e.g., necrosis) of the periarterial tissues and its relationship (i.e., location and distance) and the effect on the associated renal nerves and the correlation thereof with proxy biomarkers including renal norepinephrine concentrations and nerve-specific immunohistochemical stains (e.g., tyrosine hydroxylase). The safety evaluation of RDN technologies involves assessing for adverse effects on tissues local to the site of treatment (i.e., on the arterial wall) as well as tissues at a distance (e.g., soft tissue, veins, arterial branches, skeletal muscle, adrenal gland, ureters). Increasing experience will help to create a standardized means of examining all arterial beds subject to ablative energy and in doing so enable us to proceed to optimize the development and assessment of these emerging technologies
Impact of flow pulsatility on arterial drug distribution in stent-based therapy
Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen. Yet several factors associated with the pulsatile nature of blood flow and their impact on arterial drug deposition have not been fully investigated. We employed an integrated framework comprising bench-top and computational models to explore the factors governing the time-varying fluid dynamic environment within the vasculature and their effects on arterial drug distribution patterns. A custom-designed bench-top framework comprising a model of a single drug-eluting stent strut and a poly-vinyl alcohol-based hydrogel as a model tissue bed simulated fluid flow and drug transport under fully apposed strut settings. Bench-top experiments revealed a relative independence between drug distribution and the factors governing pulsatile flow and these findings were validated with the in silico model. Interestingly, computational models simulating suboptimal deployment settings revealed a complex interplay between arterial drug distribution, Womersley number and the extent of malapposition. In particular, for a stent strut offset from the wall, total drug deposition was sensitive to changes in the pulsatile flow environment, with this dependence increasing with greater wall displacement. Our results indicate that factors governing pulsatile luminal flow on arterial drug deposition should be carefully considered in conjunction with device deployment settings for better utilization of drug-eluting stent therapy.National Institutes of Health (U.S.) (grant NIH R01 GM-49039
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