Sample records for vascular delivery methodologies

  1. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    National Research Council Canada - National Science Library

    Chen, Bin; He, Chong


    .... We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery...

  2. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    National Research Council Canada - National Science Library

    Chen, Bin; He, Chong


    .... We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery...

  3. Viability, Advantages and Design Methodologies of M-Learning Delivery (United States)

    Zabel, Todd W.


    The purpose of this study was to examine the viability and principle design methodologies of Mobile Learning models in developing regions. Demographic and market studies were utilized to determine the viability of M-Learning delivery as well as best uses for such technologies and methods given socioeconomic and political conditions within the…

  4. The effect of mode of delivery on placental chorionic plate vascular reactivity. (United States)

    Mills, Tracey A; Baker, Philip N; Wareing, Mark


    To determine whether delivery mode influences placental chorionic plate arterial and venous vascular reactivity. Normal term placentas were obtained after vaginal delivery or cesarean section. Chorionic plate arterial and venous function was assessed by wire myography. Sodium nitroprusside-induced arterial relaxation increased post cesarean section at 20% oxygen. Decreased U46619-induced venous contraction was observed in vaginal deliveries at 7% oxygen. Sodium nitroprusside-induced relaxation increased in vaginal delivery at 20% oxygen. Delivery mode does not alter chorionic plate arterial vascular reactivity under physiological conditions, however venous reactivity was modified, a factor for consideration when interpreting functional experimental data.

  5. Nanotechnology and its relationship to interventional radiology. Part II: Drug Delivery, Thermotherapy, and Vascular Intervention. (United States)

    Power, Sarah; Slattery, Michael M; Lee, Michael J


    Nanotechnology can be defined as the design, creation, and manipulation of structures on the nanometer scale. This two-part review is intended to acquaint the interventionalist with the field of nanotechnology, and provide an overview of potential applications, while highlighting advances relevant to interventional radiology. Part 2 of the article concentrates on drug delivery, thermotherapy, and vascular intervention. In oncology, advances in drug delivery allow for improved efficacy, decreased toxicity, and greater potential for targeted therapy. Magnetic nanoparticles show potential for use in thermotherapy treatments of various tumours, and the effectiveness of radiofrequency ablation can be enhanced with nanoparticle chemotherapy agents. In vascular intervention, much work is focused on prevention of restenosis through developments in stent technology and systems for localised drug delivery to vessel walls. Further areas of interest include applications for thrombolysis and haemostasis.

  6. Nanotechnology and its relationship to interventional radiology. Part II: Drug Delivery, Thermotherapy, and Vascular Intervention.

    LENUS (Irish Health Repository)

    Power, Sarah


    Nanotechnology can be defined as the design, creation, and manipulation of structures on the nanometer scale. This two-part review is intended to acquaint the interventionalist with the field of nanotechnology, and provide an overview of potential applications, while highlighting advances relevant to interventional radiology. Part 2 of the article concentrates on drug delivery, thermotherapy, and vascular intervention. In oncology, advances in drug delivery allow for improved efficacy, decreased toxicity, and greater potential for targeted therapy. Magnetic nanoparticles show potential for use in thermotherapy treatments of various tumours, and the effectiveness of radiofrequency ablation can be enhanced with nanoparticle chemotherapy agents. In vascular intervention, much work is focused on prevention of restenosis through developments in stent technology and systems for localised drug delivery to vessel walls. Further areas of interest include applications for thrombolysis and haemostasis.

  7. Nanotechnology and its Relationship to Interventional Radiology. Part II: Drug Delivery, Thermotherapy, and Vascular Intervention.

    LENUS (Irish Health Repository)

    Power, Sarah


    Nanotechnology can be defined as the design, creation, and manipulation of structures on the nanometer scale. This two-part review is intended to acquaint the interventionalist with the field of nanotechnology, and provide an overview of potential applications, while highlighting advances relevant to interventional radiology. Part 2 of the article concentrates on drug delivery, thermotherapy, and vascular intervention. In oncology, advances in drug delivery allow for improved efficacy, decreased toxicity, and greater potential for targeted therapy. Magnetic nanoparticles show potential for use in thermotherapy treatments of various tumours, and the effectiveness of radiofrequency ablation can be enhanced with nanoparticle chemotherapy agents. In vascular intervention, much work is focused on prevention of restenosis through developments in stent technology and systems for localised drug delivery to vessel walls. Further areas of interest include applications for thrombolysis and haemostasis.

  8. Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery.

    Directory of Open Access Journals (Sweden)

    Desmond B S Pink

    Full Text Available The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM, a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2 peptide fragment or vascular endothelial growth factor (VEGF. VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors.

  9. Guided bone regeneration (GBR) utilizing injectable Vascular Endothelial Growth Factor (VEGF) delivery gel (United States)

    Kaigler, Darnell; Silva, Eduardo A.; Mooney, David J.


    Background Vascularization underlies the success of guided bone regeneration (GBR) procedures. This study evaluated the regenerative potential of GBR in combination with Vascular Endothelial Growth Factor (VEGF) delivery, via an injectable hydrogel system. Methods Critical-sized defects were created in rat calvariae and GBR procedures were performed with a collagen membrane either alone (control), plus bolus delivery of VEGF, or plus application of VEGF releasing hydrogels (VEGF - Alg). Four and eight weeks following treatment, defect sites were evaluated with microcomputed tomographic and histomorphometric analyses for blood vessel and bone formation. Results At four weeks, relative to the control condition, the bolus addition of VEGF did not affect blood vessel density within the defect site; yet, the application of the VEGF+ Alg significantly (pGBR may be a promising strategy for enhancing outcomes of GBR. PMID:22668339

  10. Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging (United States)

    Kaneda, Megan Marie

    Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

  11. Vascular bed-targeted in vivo gene delivery using tropism-modified adeno-associated viruses. (United States)

    Work, Lorraine M; Büning, Hildegard; Hunt, Ela; Nicklin, Stuart A; Denby, Laura; Britton, Nicola; Leike, Kristen; Odenthal, Margarete; Drebber, Uta; Hallek, Michael; Baker, Andrew H


    Virus-mediated gene delivery is restricted by the infectivity profile of the chosen vector. Targeting the vascular endothelium via systemic delivery has been attempted using peptides isolated in vitro (using either phage or vector display) and implicit reliance on target receptor expression in vivo. This has limited application since endothelial cells in vitro and in vivo differ vastly in receptor profiles and because of the existence of complex endothelial "zip codes" in vivo. We therefore tested whether in vivo phage display combined with adeno-associated virus (AAV) capsid modifications would allow in vivo homing to the endothelium residing in defined organs. Extensive in vivo biopanning in rats identified four consensus peptides homing to the lung or brain. Each was incorporated into the VP3 region of the AAV-2 capsid to display the peptide at the virion surface. Peptides that conferred heparan independence were shown to retarget virus to the expected vascular bed in vivo in a preferential manner, determined 28 days post-systemic injection by both virion DNA and transgene expression profiling. Our findings significantly impact the design of viral vectors for targeting individual vascular beds in vivo.

  12. Vascular nanomedicine: Site specific delivery of elastin stabilizing therapeutics to damaged arteries (United States)

    Sinha, Aditi

    Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism---pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and AAA can mitigate, partially if not wholly, the fatal consequences of both the diseases. The work presented here is motivated by the overwhelming statistics of people afflicted by elastin associated cardiovascular diseases and the unavailability of cure for the same. Overall goal of our research is to understand role of elastin degradation in cardiovascular diseases and to develop a targeted vascular drug delivery system that is minimally invasive, biodegradable, and non-toxic, that prevents elastin from degradation. Our hope is that such treatment will also help regenerate elastin, thereby providing a multi-fold treatment option for elasto-degenerative vascular diseases. For this purpose, we have first confirmed the combined role of degraded elastin and hyperglycemia in the pathogenesis of MAC. We have shown that in the absence of degraded elastin and TGF-beta1 (abundantly present in diabetic arteries) vascular smooth muscle cells maintain their homeostatic state, regardless of environmental glucose concentrations. However simultaneous exposure to glucose, elastin peptides and TGF-beta1 causes the pathological transgenesis of vascular cells to osteoblast-like cells. We show that plant derived polyphenols bind to vascular elastin with great affinity resulting in

  13. ROS-mediated vascular homeostatic control of root-to-shoot soil Na delivery in Arabidopsis. (United States)

    Jiang, Caifu; Belfield, Eric J; Mithani, Aziz; Visscher, Anne; Ragoussis, Jiannis; Mott, Richard; Smith, J Andrew C; Harberd, Nicholas P


    Sodium (Na) is ubiquitous in soils, and is transported to plant shoots via transpiration through xylem elements in the vascular tissue. However, excess Na is damaging. Accordingly, control of xylem-sap Na concentration is important for maintenance of shoot Na homeostasis, especially under Na stress conditions. Here we report that shoot Na homeostasis of Arabidopsis thaliana plants grown in saline soils is conferred by reactive oxygen species (ROS) regulation of xylem-sap Na concentrations. We show that lack of A. thaliana respiratory burst oxidase protein F (AtrbohF; an NADPH oxidase catalysing ROS production) causes hypersensitivity of shoots to soil salinity. Lack of AtrbohF-dependent salinity-induced vascular ROS accumulation leads to increased Na concentrations in root vasculature cells and in xylem sap, thus causing delivery of damaging amounts of Na to the shoot. We also show that the excess shoot Na delivery caused by lack of AtrbohF is dependent upon transpiration. We conclude that AtrbohF increases ROS levels in wild-type root vasculature in response to raised soil salinity, thereby limiting Na concentrations in xylem sap, and in turn protecting shoot cells from transpiration-dependent delivery of excess Na.

  14. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery

    DEFF Research Database (Denmark)

    Storkebaum, Erik; Ruiz de Almodovar, Carmen; Meens, Merlijn


    BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( ...... for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients.......( partial differential/ partial differential) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic...... nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions. CONCLUSIONS: These findings uncover a novel role...

  15. Using the Crowd of Taxis to Last Mile Delivery in E-commerce: a Methodological Research


    CHEN, CHAO; Pan, Shenle


    International audience; Crowdsourcing is garnering increased attention in freight transport area, mainly applied in internet-based services to city logistics. However, scientific research, especially methodology for application is still rare in the literature. This paper aims to fill this gap and to propose a methodological approach of applying crowdsourcing solution to Last Mile Delivery in E-commerce environment. The proposed solution is based on taxi fleet in city and a transport network c...

  16. Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery. (United States)

    Chicoine, L G; Montgomery, C L; Bremer, W G; Shontz, K M; Griffin, D A; Heller, K N; Lewis, S; Malik, V; Grose, W E; Shilling, C J; Campbell, K J; Preston, T J; Coley, B D; Martin, P T; Walker, C M; Clark, K R; Sahenk, Z; Mendell, J R; Rodino-Klapac, L R


    Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.

  17. Amplatzer Vascular Plug Anchoring Technique to Stabilize the Delivery System for Microcoil Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Onozawa, Shiro, E-mail:; Murata, Satoru, E-mail: [Nippon Medical School, Department of Radiology/Center for Advanced Medical Technology (Japan); Mine, Takahiko, E-mail: [Tokai University School of Medicine, Department of Radiology, Tokai University Hachioji Hospital (Japan); Sugihara, Fumie, E-mail:; Yasui, Daisuke, E-mail:; Kumita, Shin-ichiro, E-mail: [Nippon Medical School, Department of Radiology/Center for Advanced Medical Technology (Japan)


    PurposeTo evaluate the feasibility of a novel embolization technique, the Amplatzer vascular plug (AVP) anchoring technique, to stabilize the delivery system for microcoil embolization.Materials and methodsThree patients were enrolled in this study, including two cases of internal iliac artery aneurysms and one case of internal iliac arterial occlusion prior to endovascular aortic repair. An AVP was used in each case for embolization of one target artery, and the AVP was left in place. The AVP detachment wire was then used as an anchor to stabilize the delivery system for microcoil embolization to embolize the second target artery adjacent to the first target artery. The microcatheter for the microcoils was inserted parallel to the AVP detachment wire in the guiding sheath or catheter used for the AVP.ResultsThe AVP anchoring technique was achieved and the microcatheter was easily advanced to the second target artery in all three cases.ConclusionThe AVP anchoring technique was found to be feasible to advance the microcatheter into the neighboring artery of an AVP-embolized artery.

  18. Multi-ligand nanoparticles for targeted drug delivery to the injured vascular wall (United States)

    Kona, Soujanya

    Pathological conditions like coronary artery disease, acute myocardial infarction, stroke, and peripheral artery diseases as well as cardiovascular interventions used in the treatment of coronary artery diseases such as angioplasty and stenting damage/injure the blood vessel wall, leading to inflamed or activated endothelial cells that have been implicated in events leading to thrombosis, inflammation, and restenosis. Oral administration of anti-coagulant and anti-inflammatory drugs causes systemic toxicity, bleeding, patient incompliance, and inadequate amounts of drugs at the injured area. Though drug-eluting stents have shown therapeutic benefits, complications such as in-stent restenosis and late thrombosis still remain and are a cause for concern. Rapid growth in the field of nanotechnology and nanoscience in recent years has paved the way for new targeted and controlled drug delivery strategies. In this perspective, the development of biodegradable nanoparticles for targeted intracellular drug delivery to the inflamed endothelial cells may offer an improved avenue for treatment of cardiovascular diseases. The major objective of this research was to develop "novel multi-ligand nanoparticles," as drug carriers that can efficiently target and deliver therapeutic agents to the injured/inflamed vascular cells under dynamic flow conditions. Our approach mimics the natural binding ability of platelets to injured/activated endothelial cells through glycoprotein Ib (GPIb) bound to P-selectin expressed on inflamed endothelial cells and to the subendothelium through GPIb binding to von Willebrand factor (vWF) deposited onto the injured vascular wall. Our design also exploits the natural cell membrane translocation ability of the internalizing cell peptide - trans-activating transcriptor (TAT) to enhance the nanoparticle uptake by the targeted cells. Our hypothesis is that these multi-ligand nanoparticles would show an increased accumulation at the injury site since GPIb

  19. Spatially discrete thermal drawing of biodegradable microneedles for vascular drug delivery. (United States)

    Choi, Chang Kuk; Lee, Kang Ju; Youn, Young Nam; Jang, Eui Hwa; Kim, Woong; Min, Byung-Kwon; Ryu, WonHyoung


    Spatially discrete thermal drawing is introduced as a novel method for the fabrication of biodegradable microneedles with ultra-sharp tip ends. This method provides the enhanced control of microneedle shapes by spatially controlling the temperature of drawn polymer as well as drawing steps and speeds. Particular focus is given on the formation of sharp tip ends of microneedles at the end of thermal drawing. Previous works relied on the fracture of polymer neck by fast drawing that often causes uncontrolled shapes of microneedle tips. Instead, this approach utilizes the surface energy of heated polymer to form ultra-sharp tip ends. We have investigated the effect of such temperature control, drawing speed, and drawing steps in thermal drawing process on the final shape of microneedles using biodegradable polymers. XRD analysis was performed to analyze the effect of thermal cycle on the biodegradable polymer. Load-displacement measurement also showed the dependency of mechanical strengths of microneedles on the microneedle shapes. Ex vivo vascular tissue insertion and drug delivery demonstrated microneedle insertion to tunica media layer of canine aorta and drug distribution in the tissue layer. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Mesoporous silica particle-PLA-PANI hybrid scaffolds for cell-directed intracellular drug delivery and tissue vascularization (United States)

    Shokry, Hussein; Vanamo, Ulriika; Wiltschka, Oliver; Niinimäki, Jenni; Lerche, Martina; Levon, Kalle; Linden, Mika; Sahlgren, Cecilia


    Instructive materials are expected to revolutionize stem cell based tissue engineering. As many stem cell cues have adverse effects on normal tissue homeostasis, there is a need to develop bioactive scaffolds which offer locally retained and cell-targeted drug delivery for intracellular release in targeted cell populations. Further, the scaffolds need to support vascularization to promote tissue growth and function. We have developed an electrospun PLA-PANI fiber scaffold, and incorporated mesoporous silica nanoparticles within the scaffold matrix to obtain cell-targeted and localized drug delivery. The isotropy of the scaffold can be tuned to find the optimal morphology for a given application and the scaffold is electroactive to support differentiation of contractile tissues. We demonstrate that there is no premature drug release from particles under physiological conditions over a period of one week and that the drug is released upon internalization of particles by cells within the scaffold. The scaffold is biocompatible, supports muscle stem cell differentiation and cell-seeded scaffolds are vascularized in vivo upon transplantation on the chorioallantoic membrane of chicken embryos. The scaffold is a step towards instructive biomaterials for local control of stem cell differentiation, and tissue formation supported by vascularization and without adverse effects on the homeostasis of adjacent tissues due to diffusion of biological cues.Instructive materials are expected to revolutionize stem cell based tissue engineering. As many stem cell cues have adverse effects on normal tissue homeostasis, there is a need to develop bioactive scaffolds which offer locally retained and cell-targeted drug delivery for intracellular release in targeted cell populations. Further, the scaffolds need to support vascularization to promote tissue growth and function. We have developed an electrospun PLA-PANI fiber scaffold, and incorporated mesoporous silica nanoparticles within

  1. [Implementation methodology of practices based on scientific evidence for assistance in natural delivery: a pilot study]. (United States)

    Côrtes, Clodoaldo Tentes; Santos, Rafael Cleison Silva Dos; Caroci, Adriana de Souza; Oliveira, Sheyla Guimarães; Oliveira, Sonia Maria Junqueira Vasconcelos de; Riesco, Maria Luiza Gonzalez


    Presenting methodology for transferring knowledge to improve maternal outcomes in natural delivery based on scientific evidence. An intervention study conducted in the maternity hospital of Itapecerica da Serra, SP, with 50 puerperal women and 102 medical records from July to November 2014. The PACES tool from Joanna Briggs Institute, consisting of pre-clinical audit (phase 1), implementation of best practice (phase 2) and Follow-up Clinical Audit (phase 3) was used. Data were analyzed by comparing results of phases 1 and 3 with Fisher's exact test and a significance level of 5%. The vertical position was adopted by the majority of puerperal women with statistical difference between phases 1 and 3. A significant increase in bathing/showering, walking and massages for pain relief was found from the medical records. No statistical difference was found in other practices and outcomes. Barriers and difficulties in the implementation of evidence-based practices have been identified. Variables were refined, techniques and data collection instruments were verified, and an intervention proposal was made. The study found possibilities for implementing a methodology of practices based on scientific evidence for assistance in natural delivery.

  2. An integrated methodology for process improvement and delivery system visualization at a multidisciplinary cancer center. (United States)

    Singprasong, Rachanee; Eldabi, Tillal


    Multidisciplinary cancer centers require an integrated, collaborative, and stream-lined workflow in order to provide high quality of patient care. Due to the complex nature of cancer care and continuing changes to treatment techniques and technologies, it is a constant struggle for centers to obtain a systemic and holistic view of treatment workflow for improving the delivery systems. Project management techniques, Responsibility matrix and a swim-lane activity diagram representing sequence of activities can be combined for data collection, presentation, and evaluation of the patient care. This paper presents this integrated methodology using multidisciplinary meetings and walking the route approach for data collection, integrated responsibility matrix and swim-lane activity diagram with activity time for data representation and 5-why and gap analysis approach for data analysis. This enables collection of right detail of information in a shorter time frame by identifying process flaws and deficiencies while being independent of the nature of the patient's disease or treatment techniques. A case study of a multidisciplinary regional cancer centre is used to illustrate effectiveness of the proposed methodology and demonstrates that the methodology is simple to understand, allowing for minimal training of staff and rapid implementation. © 2011 National Association for Healthcare Quality.

  3. The Application of Failure Modes and Effects Analysis Methodology to Intrathecal Drug Delivery for Pain Management. (United States)

    Saulino, Michael F; Patel, Teresa; Fisher, Stanley P


    This study aimed to utilize failure modes and effects analysis (FMEA) to transform clinical insights into a risk mitigation plan for intrathecal (IT) drug delivery in pain management. The FMEA methodology, which has been used for quality improvement, was adapted to assess risks (i.e., failure modes) associated with IT therapy. Ten experienced pain physicians scored 37 failure modes in the following categories: patient selection for therapy initiation (efficacy and safety concerns), patient safety during IT therapy, and product selection for IT therapy. Participants assigned severity, probability, and detection scores for each failure mode, from which a risk priority number (RPN) was calculated. Failure modes with the highest RPNs (i.e., most problematic) were discussed, and strategies were proposed to mitigate risks. Strategic discussions focused on 17 failure modes with the most severe outcomes, the highest probabilities of occurrence, and the most challenging detection. The topic of the highest-ranked failure mode (RPN = 144) was manufactured monotherapy versus compounded combination products. Addressing failure modes associated with appropriate patient and product selection was predicted to be clinically important for the success of IT therapy. The methodology of FMEA offers a systematic approach to prioritizing risks in a complex environment such as IT therapy. Unmet needs and information gaps are highlighted through the process. Risk mitigation and strategic planning to prevent and manage critical failure modes can contribute to therapeutic success. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

  4. Cerebral microbleed detection and mapping: principles, methodological aspects and rationale in vascular dementia. (United States)

    Charidimou, Andreas; Jäger, Hans R; Werring, David J


    Cerebral microbleeds (CMBs) have emerged as an important new imaging manifestation of sporadic cerebral small vessel diseases - mainly hypertensive arteriopathy and cerebral amyloid angiopathy - which are highly prevalent in the elderly and have a critical role in vascular cognitive impairment and dementia. With the development of MRI techniques that are exquisitely sensitive to the products of bleeding, including T2*-weighted gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI), CMBs have been detected in ever-increasing numbers of patients, including those with vascular cognitive impairment and dementia, as well as in population-based samples of healthy elderly people. Our increased ability to image CMBs and hence to see the development and progression of cerebral small vessel disease raises many clinical and pathophysiological questions about the mechanisms, diagnosis and monitoring of cognitive impairment. In order to tackle these questions, it is important to be able to reliably detect, define and map CMBs in the brains of elderly people. In this review, we consider radiological detection methods, criteria for defining CMBs (including a practical approach to the identification of CMB "mimics"), and the use of standardised rating scales. We also briefly discuss the potential for automatically detecting and quantitatively mapping CMBs in future. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Heating drug delivery to vascular wall with Rhodamine B and fluorescence labeled Paclitaxel ranging 50 to 70°C: ex vivo study (United States)

    Homma, R.; Shinozuka, M.; Shimazaki, N.; Arai, T.


    We studied heating drug delivery to vascular wall with Rhodamine B ranging 50 to 70°C ex vivo study. Porcine carotid artery was dipped in the heated Rhodamine B solution in 15 s and then cooled by 37°C saline. Rhodamine B concentration distribution in the vascular wall cross-section was measured by a fluorescence microscope using 550 nm for excitation and 620 nm emission for fluorescence detection. The total amount of measured fluorescence in the vascular wall was calculated as a indication of delivered Rhodamine B quantity. The delivered Rhodamine B quantity was increased with increasing heating temperature with 50 to 70°C. In the cases of 60 to 70°C heating, the delivered Rhodamine B quantity was 3.1 to 23.3 fold by that of 37°C. Defined penetration depth of the delivered Rhodamine B in the vascular wall was also significantly increased with 65°C and 70°C heating. We also studied heating drug delivery to the vascular wall with fluorescence labeled Paclitaxel with 70°C in 15 s and 60 s heating ex vivo. In both contact duration, the delivered Paclitaxel quantity was increased. To understand these drug delivery enhancement effects, we investigated the vascular cross-sectional structure change by the heating. Some holes over 50 nm in diameter appeared on the internal elastic lamina with 70°C heating. We prospected that vascular surface structure change by the heating might enhance drug delivery to the vascular wall.

  6. A PEGylated platelet free plasma hydrogel based composite scaffold enables stable vascularization and targeted cell delivery for volumetric muscle loss. (United States)

    Aurora, Amit; Wrice, Nicole; Walters, Thomas J; Christy, Robert J; Natesan, Shanmugasundaram


    Extracellular matrix (ECM) scaffolds are being used for the clinical repair of soft tissue injuries. Although improved functional outcomes have been reported, ECM scaffolds show limited tissue specific remodeling response with concomitant deposition of fibrotic tissue. One plausible explanation is the regression of blood vessels which may be limiting the diffusion of oxygen and nutrients across the scaffold. Herein we develop a composite scaffold as a vasculo-inductive platform by integrating PEGylated platelet free plasma (PFP) hydrogel with a muscle derived ECM scaffold (m-ECM). In vitro, adipose derived stem cells (ASCs) seeded onto the composite scaffold differentiated into two distinct morphologies, a tubular network in the hydrogel, and elongated structures along the m-ECM scaffold. The composite scaffold showed a high expression of ITGA5, ITGB1, and FN and a synergistic up-regulation of ang1 and tie-2 transcripts. The in vitro ability of the composite scaffold to provide extracellular milieu for cell adhesion and molecular cues to support vessel formation was investigated in a rodent volumetric muscle loss (VML) model. The composite scaffold delivered with ASCs supported robust and stable vascularization. Additionally, the composite scaffold supported increased localization of ASCs in the defect demonstrating its ability for localized cell delivery. Interestingly, ASCs were observed homing in the injured muscle and around the perivascular space possibly to stabilize the host vasculature. In conclusion, the composite scaffold delivered with ASCs presents a promising approach for scaffold vascularization. The versatile nature of the composite scaffold also makes it easily adaptable for the repair of soft tissue injuries. Decellularized extracellular matrix (ECM) scaffolds when used for soft tissue repair is often accompanied by deposition of fibrotic tissue possibly due to limited scaffold vascularization, which limits the diffusion of oxygen and nutrients

  7. Tumor vascular endothelium : Barrier or target in tumor directed drug delivery and immunotherapy

    NARCIS (Netherlands)

    Molema, Ingrid; de Leij, Lou; Meijer, D.K F

    The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immunomodulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and

  8. Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy. (United States)

    Galan, Alba; Barcelona, Pablo F; Nedev, Hinyu; Sarunic, Marinko V; Jian, Yifan; Saragovi, H Uri


    The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. We compared the pharmacokinetics of a single 40 μg subconjunctival (SCJ) depot to the reported effective 5 μg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.

  9. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Chicoine Louis G


    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1 A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2 an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3 the use of viral doses to accommodate current limitations imposed by vector production methods; 4 and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. Methods The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL. The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Results Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month, 91.3 ± 3.1 (2 months, and 89.6 ± 1.6% (3 months. rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month, 78.9 ± 7.4 (2 months, and 81.2 ± 6.2% (3 months transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month, 2.1 ± 0.8 (2 months, and 2.1 ± 0.7% (3 months] by vascular delivery. Micro

  10. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. (United States)

    Rodino-Klapac, Louise R; Janssen, Paul M L; Montgomery, Chrystal L; Coley, Brian D; Chicoine, Louis G; Clark, K Reed; Mendell, Jerry R


    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a) that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL). The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 +/- 0.9 (1 month), 91.3 +/- 3.1 (2 months), and 89.6 +/- 1.6% (3 months). rAAV6.micro-dystrophin treated animals demonstrated 87.7 +/- 6.8 (1 month), 78.9 +/- 7.4 (2 months), and 81.2 +/- 6.2% (3 months) transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 +/- 0.3 (1 month), 2.1 +/- 0.8 (2 months), and 2.1 +/- 0.7% (3 months)] by vascular delivery. Micro-dystrophin delivered by rAAV8 and

  11. Optimized delivery radiological reports: applying Six Sigma methodology to a radiology department. (United States)

    Cavagna, Enrico; Berletti, Riccardo; Schiavon, Francesco; Scarsi, Barbara; Barbato, Giuseppe


    To optimise the process of reporting and delivering radiological examinations with a view to achieving 100% service delivery within 72 hours to outpatients and 36 hours to inpatients. To this end, we used the Six Sigma method which adopts a systematic approach and rigorous statistical analysis to analyse and improve processes, by reducing variability and minimising errors. More specifically, our study focused on the process of radiological report creation, from the end of the examination to the time when the report is made available to the patient, to examine the bottlenecks and identify the measures to be taken to improve the process. Six Sigma uses a five-step problem-solving process called DMAIC, an acronym for Define, Measure, Analyze, Improve and Control. The first step is to define the problem and the elements crucial to quality, in terms of Total Quality Control. Next, the situation is analysed to identify the root causes of the problem and determine which of these is most influential. The situation is then improved by implementing change. Finally, to make sure that the change is long-lasting, measures are taken to sustain the improvements and obtain long-term control. In our case we analysed all of the phases the report passes through before reaching the user, and studied the impact of voice-recognition reporting on the speed of the report creation process. Analysis of the information collected showed that the tools available for report creation (dictaphone, voice-recognition system) and the transport of films and reports were the two critical elements on which to focus our efforts. Of all the phases making up the process, reporting (from end of examination to end of reporting) and distribution (from the report available to administrative staff to report available to the patient) account for 90% of process variability (73% and 17%, respectively). We further found that the reports dictated into a voice-recognition reporting system are delivered in 45 hours

  12. Transient disruption of vascular barriers using focused ultrasound and microbubbles for targeted drug delivery in the brain (United States)

    Aryal, Muna

    The physiology of the vasculature in the central nervous system (CNS) which includes the blood-brain-barrier (BBB) and other factors, prevents the transport of most anticancer agents to the brain and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels (blood-tumor barrier; BTB), along with several other factors, creates additional hurdles for drug treatment of brain tumors. Different methods have been used to bypass the BBB/BTB, but they have their own limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Magnetic Resonance Imaging guided Focused Ultrasound (MRIgFUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and BTB. The purpose of this thesis was to use this alternative approach to deliver chemotherapeutic agents through the BBB/BTB for brain tumor treatment in a rodent model to overcome the hinderances encountered in prior approaches tested for drug delivery in the CNS. The results presented in thesis demonstrate that MRIgFUS can be used to achieve consistent and reproducible BBB/BTB disruption in rats. It enabled us to achieve clinically-relevant concentrations of doxorubicin (~ 4.8+/-0.5 microg/g) delivered to the brain with the sonication parameters (0.69 MHz; 0.55 MPa; 10 ms bursts; 1 Hz PRF; 60 s duration), microbubble concentration (Definity, 10 microl/kg), and liposomoal doxorubicin (Lipo-DOX) dose (5.67 mg/kg) used. The resulting doxorubicin concentration was reduced by 32% when the agent was injected 10 minute after the last sonication. Three weekly sessions of FUS and Lipo-DOX appeared to be safe in the rat brain, despite some minor tissue damage. Importantly, the severe neurotoxicity seen in earlier works using other approaches does not appear to occur with delivery via FUS-BBB disruption. The resuls from three weekly treatments of FUS and Lipo-DOX in a rat glioma model are highly

  13. A Methodology for Evaluating User Perceptions of the Delivery of ICT Services: a comparative study of six UK local authorities

    Directory of Open Access Journals (Sweden)

    Les Worrall


    Full Text Available Evaluating and managing the effective delivery of ICT services is an issue that has been brought into sharper relief recently. This has been particularly prevalent in the UK public sector where the growing emphasis on formalised client-contractor relationships, outsourcing and benchmarking (both between local authorities and between local authorities and private sector organisations has meant that the definition of service standards and agreeing performance criteria has attracted considerable practitioner attention. This research is based on 295 interviews conducted in six UK local authorities. The investigation used both gap analysis and perceptual mapping techniques to develop an understanding of the aspects of ICT service delivery that users' value most in conjunction with an assessment of how well they perceive their ICT department is performing on these criteria. The paper exposes considerable differences in the relative performance of the six local authorities from both the gap analysis and the perceptual mapping elements of the investigation. The methodology is shown to provide an effective way of identifying key performance issues from the user perspective and benchmarking service performance across organisations.

  14. Effect of microemulsions on transdermal delivery of citalopram: optimization studies using mixture design and response surface methodology. (United States)

    Huang, Chi-Te; Tsai, Ming-Jun; Lin, Yu-Hsuan; Fu, Yaw-Sya; Huang, Yaw-Bin; Tsai, Yi-Hung; Wu, Pao-Chu


    The aim of this study was to evaluate the potential of microemulsions as a drug vehicle for transdermal delivery of citalopram. A computerized statistical technique of response surface methodology with mixture design was used to investigate and optimize the influence of the formulation compositions including a mixture of Brij 30/Brij 35 surfactants (at a ratio of 4:1, 20%-30%), isopropyl alcohol (20%-30%), and distilled water (40%-50%) on the properties of the drug-loaded microemulsions, including permeation rate (flux) and lag time. When microemulsions were used as a vehicle, the drug permeation rate increased significantly and the lag time shortened significantly when compared with the aqueous control of 40% isopropyl alcohol solution containing 3% citalopram, demonstrating that microemulsions are a promising vehicle for transdermal application. With regard to the pharmacokinetic parameters of citalopram, the flux required for the transdermal delivery system was about 1280 μg per hour. The microemulsions loaded with citalopram 3% and 10% showed respective flux rates of 179.6 μg/cm(2) and 513.8 μg/cm(2) per hour, indicating that the study formulation could provide effective therapeutic concentrations over a practical application area. The animal study showed that the optimized formulation (F15) containing 3% citalopram with an application area of 3.46 cm(2) is able to reach a minimum effective therapeutic concentration with no erythematous reaction.

  15. Formulation and optimization of fast dissolving intraoral drug delivery system for clobazam using response surface methodology

    Directory of Open Access Journals (Sweden)

    Rajni Bala


    Full Text Available Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. It is better tolerated and less sedating than other benzodiazepines. Absorption of the drug can be impacted by oral fast dissolving dosage form; this may have implications for epilepsy in pediatrics and those having difficulty in swallowing tablets/capsules resulting in improved patient compliance. The purpose of the present investigation was to formulate and optimize clobazam oro-dissolving tablets by direct compression method using response surface methodology (RSM. Oro-dispersible tablets of clobazam were prepared by direct compression method using crospovidone (2-6% as a superdisintegrant, microcrystalline cellulose (MCC (20-40% was used as diluents along with directly compressible mannitol to enhance mouth feel. A 3 2 full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and MCC over the independent variables disintegration time, wetting time and percent drug release. Disintegration time showed by all formulations was found to be in the range of 24.3-193 s based on evaluation parameters the formulation containing 6% of crospovidone and 30% of MCC showed promising performance against all other formulations. The results demonstrated that the RSM could efficiently be applied for the formulation of clobazam oro-dispersible tablets; therefore, constitute an advance in the management of epileptic attacks.

  16. Linear-motion tattoo machine and prefabricated needle sets for the delivery of plant viruses by vascular puncture inoculation (United States)

    Vascular puncture inoculation (VPI) of plant viruses previously has been conducted either manually or by use of a commercial engraving tool and laboratory-fabricated needle arrays. In an effort to improve this technique, a linear-motion tattoo machine driving industry-standard needle arrays was tes...

  17. Relationship between recurrent miscarriage and early preterm delivery and recurrent events in patients with manifest vascular disease : The SMART study

    NARCIS (Netherlands)

    Heida, Karst Y; Koster, Maria PH; Franx, Arie; Veerbeek, Jan HW; Westerink, Jan; Bots, Michiel L; Spiering, Wilko

    BACKGROUND: Women with a complication of pregnancy are at increased risk of cardiovascular morbidity and mortality later in life. Yet, information on risk of recurrent events in women with a previous cardiovascular event is lacking. We aimed to assess the relationship between early preterm delivery,

  18. A fibrin patch-based enhanced delivery of human embryonic stem cell-derived vascular cell transplantation in a porcine model of postinfarction LV remodeling (United States)

    Xiong, Qiang; Hill, Katherine L.; Li, Qinglu; Suntharalingam, Piradeep; Mansoor, Abdul; Wang, Xiaohong; Jameel, Mohammad Nurulqadr; Zhang, Pengyuan; Swingen, Cory; Kaufman, Dan S.; Zhang, Jianyi


    It is unknown how to use hESC to effectively treat hearts with postinfarction LV remodeling. Using a porcine model of postinfarction LV remodeling, this study examined the functional improvement of enhanced delivery of combined transplantation of hESC-derived endothelial cells (ECs) and hESC-derived smooth muscle cells (SMCs) with a fibrin 3D porous scaffold biomatrix. To facilitate tracking the transplanted cells, the hESCs were genetically modified to stably express green fluorescent protein and luciferase (GFP/Luc). Myocardial infarction (MI) was created by ligating the 1st diagonal coronary artery for 60 min followed by reperfusion. Two million each of GFP/Luc hESC-derived ECs and SMCs were seeded in the 3D porous biomatrix patch and applied to the region of ischemia/reperfusion for cell group (MI+P+C, n=6), whereas biomatrix without cell (MI+P, n=5), or saline only (MI, n=5) were applied to control group hearts with same coronary artery ligation. Functional outcome (1 and 4 weeks follow-up) of stem cell transplantation was assessed by cardiac magnetic resonance imaging (MRI). The transplantation of hESC-derived vascular cells resulted in significant LV functional improvement. Significant engraftment of hESC-derived cells was confirmed by both in vivo and ex vivo bioluminescent imaging (BLI). The mechanism underlying the functional beneficial effects of cardiac progenitor transplantation is attributed to the increased neovascularization. These findings demonstrate a promising therapeutic potential of using these hESC-derived vascular cell types and the mode of patch delivery. PMID:21732493

  19. Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp. (United States)

    Kuang, Rong; Zhang, Zhanpeng; Jin, Xiaobing; Hu, Jiang; Shi, Songtao; Ni, Longxing; Ma, Peter X


    Dental pulp infection and necrosis are widespread diseases. Conventional endodontic treatments result in a devitalized and weakened tooth. In this work, we synthesized novel star-shaped polymer to self-assemble into unique nanofibrous spongy microspheres (NF-SMS), which were used to carry human dental pulp stem cells (hDPSCs) into the pulp cavity to regenerate living dental pulp tissues. It was found that NF-SMS significantly enhanced hDPSCs attachment, proliferation, odontogenic differentiation and angiogenesis, as compared to control cell carriers. Additionally, NF-SMS promoted vascular endothelial growth factor (VEGF) expression of hDPSCs in a 3D hypoxic culture. Hypoxia-primed hDPSCs/NF-SMS complexes were injected into the cleaned pulp cavities of rabbit molars for subcutaneous implantation in mice. After 4 weeks, the hypoxia group significantly enhanced angiogenesis inside the pulp chamber and promoted the formation of ondontoblast-like cells lining along the dentin-pulp interface, as compared to the control groups (hDPSCs alone group, NF-SMS alone group, and hDPSCs/NF-SMS group pre-cultured under normoxic conditions). Furthermore, in an in situ dental pulp repair model in rats, hypoxia-primed hDPSCs/NF-SMS were injected to fully fill the pulp cavity and regenerate pulp-like tissues with a rich vasculature and a histological structure similar to the native pulp. Vascularization is key to the regeneration of many vital tissues. However, it is challenging to create a suitable microenvironment for stem cells to regenerate vascularized tissue structure. This manuscript reports a novel star-shaped block copolymer that self-assembles into unique nanofibrous spongy microspheres, which as an injectable scaffold recapitulate the cell-cell and cell-matrix interactions in development. Using a clinically-relevant surgical procedure and a hypoxic treatment, the nanofibrous spongy microspheres were used to deliver stem cells and successfully regenerate dental pulp with a

  20. Poly(lactic-co-glycolic Acid/Nanohydroxyapatite Scaffold Containing Chitosan Microspheres with Adrenomedullin Delivery for Modulation Activity of Osteoblasts and Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Lin Wang


    Full Text Available Adrenomedullin (ADM is a bioactive regulatory peptide that affects migration and proliferation of diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. This study investigated the effects of sustained release of ADM on the modulation activity of osteoblasts and vascular endothelial cells in vitro. Chitosan microspheres (CMs were developed for ADM delivery. Poly(lactic-co-glycolic acid and nano-hydroxyapatite were used to prepare scaffolds containing microspheres with ADM. The CMs showed rough surface morphology and high porosity, and they were well-distributed. The scaffolds exhibited relatively uniform pore sizes with interconnected pores. The addition of CMs improved the mechanical properties of the scaffolds without affecting their high porosity. In vitro degradation tests indicated that the addition of CMs increased the water absorption of the scaffolds and inhibited pH decline of phosphate-buffered saline medium. The expression levels of osteogenic-related and angiogenic-related genes were determined in MG63 cells and in human umbilical vein endothelial cells cultured on the scaffolds, respectively. The expression levels of osteogenic-related and angiogenic-related proteins were also detected by western blot analysis. Their expression levels in cells were improved on the ADM delivery scaffolds at a certain time point. The in vitro evaluation suggests that the microsphere-scaffold system is suitable as a model for bone tissue engineering.

  1. Bio-hybrid silk fibroin/calcium phosphate/PLGA nanocomposite scaffold to control the delivery of vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Farokhi, Mehdi, E-mail: [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mottaghitalab, Fatemeh, E-mail: [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University (TMU), Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Hadjati, Jamshid; Azami, Mahmoud [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)


    This study investigated the efficacy of bio-hybrid silk fibroin/Calcium phosphate/PLGA nanocomposite scaffold as vascular endothelial growth factor (VEGF) delivery system. The scaffold was fabricated using freeze-drying and electrospinning. Here, we highlight the structural changes of the scaffold using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and differential scanning calorimetry (DSC). The uniform dispersion of calcium phosohate (CaP) powder within silk fibroin (SF) solution was also confirmed using Zeta potential analysis. Moreover, good biocompatibility of osteoblast cells next to the scaffold was approved by cell adhesion, proliferation and alkaline phosphatase production. The release profile of VEGF during 28 days has established the efficacy of the scaffold as a sustained delivery system. The bioactivity of the released VEGF was maintained about 83%. The histology analysis has shown that the new bone tissue formation happened in the defected site after 10 weeks of implantation. Generally, our data showed that the fabricated scaffold could be considered as an effective scaffold for bone tissue engineering applications. - Highlights: • Silk fibroin/calcium phosphate/PLGA scaffold was successfully fabricated using freeze-drying and electrospinning. • The scaffold could control the release of VEGF during 28 days. • The bioactivity of electrospun VEGF was above 80%. • VEGF loaded scaffold could induce bone regeneration after 10 weeks in rabbit.

  2. Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer. (United States)

    Yang, Tianzhi; Fogarty, Brittany; LaForge, Bret; Aziz, Salma; Pham, Thuy; Lai, Leanne; Bai, Shuhua


    Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.

  3. Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold, Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration

    Directory of Open Access Journals (Sweden)

    Hang Zhao


    Full Text Available The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2 and basic fibroblast growth factor (bFGF from nano-composite scaffolds (PLGA/PCL/nHA loaded with vascular stents (PLCL/Col/nHA for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs, bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA. AlamarBlue assay and alkaline phosphatase (ALP activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01. In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large

  4. Optimization of self nanoemulsifying drug delivery system for poorly water-soluble drug using response surface methodology

    DEFF Research Database (Denmark)

    Ren, Shan; Mu, Huiling; Alchaer, Fadi


    There is an increasing interest on self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of poorly water-soluble drugs. However, development of SNEDDS is often driven by empiric, pseudo-ternary diagrams and solubility of drugs, and it is lacking a systematic approach for evaluating...

  5. Intracavernous delivery of stromal vascular fraction restores erectile function through production of angiogenic factors in a mouse model of cavernous nerve injury. (United States)

    Song, Kang-Moon; Jin, Hai-Rong; Park, Jin-Mi; Choi, Min Ji; Kwon, Mi-Hye; Kwon, Ki-Dong; Batbold, Dulguun; Yin, Guo Nan; Kim, Woo Jean; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu


    Erectile dysfunction (ED) is a major complication of radical prostatectomy. Men with radical prostatectomy-induced ED respond less positively to oral phosphodiesterase-5 inhibitors. The study aims to examine whether and how stromal vascular fraction (SVF) restores erectile function in mice with cavernous nerve injury (CNI). Twelve-week-old male C57BL/6J mice were used and the animals were distributed into five groups: sham operation group and CNI group receiving a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 10(4) , 1 × 10(5) , or 3 × 10(5) cells/20 μL, respectively). SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice. Two weeks after injection, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to platelet/endothelial cell adhesion molecule-1, phosphohistone H3, and phosphorylated endothelial nitric oxide synthase (phospho-eNOS). We also performed Western blot for angiopoietin-1 (Ang-1), vascular endothelial growth factor-A, hepatocyte growth factor, phospho-eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of SVF restored erectile function in a dose-dependent manner in CNI mice. The highest erectile response was noted at a dose of 3 × 10(5) cells, for which the response was comparable with that in the sham operation group. Local delivery of SVF significantly increased the expression of angiogenic factor proteins and induced cavernous endothelial cell proliferation and eNOS phosphorylation compared with that in the PBS-treated CNI group. SVF-induced promotion of cavernous angiogenesis and erectile function was diminished in the presence of soluble antibody to Tie2, a receptor tyrosine kinase of Ang-1. Secretion of angiogenic factors from SVF is an important mechanism by which SVF induces cavernous endothelial regeneration and restores erectile function. These findings suggest that cavernous endothelial regeneration by

  6. Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases. (United States)

    Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J


    Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety. © 2013 American Physiological Society. Compr Physiol 3:1749-1779, 2013.

  7. Complementary therapeutic effects of dual delivery of insulin-like growth factor-1 and vascular endothelial growth factor by gelatin microspheres in experimental heart failure. (United States)

    Cittadini, Antonio; Monti, Maria Gaia; Petrillo, Valentina; Esposito, Giovanni; Imparato, Giorgia; Luciani, Alessia; Urciuolo, Francesco; Bobbio, Emanuele; Natale, Carlo F; Saccà, Luigi; Netti, Paolo A


    Strategies to prevent adverse left ventricular (LV) remodelling after myocardial infarction have included several traditional approaches and novel cell-based or gene therapies. Delivery of growth factors in post-infarction heart failure has emerged as a valuable alternative strategy. Our aim was to investigate the effects of sequential release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) from biodegradable gelatin microspheres in experimental heart failure. Gelatin hydrogel microspheres were known to guarantee a sustained release of encapsulated growth factors, characterized by an initial burst followed by a slower release. Rats with moderate myocardial infarction were randomized to receive empty microspheres (MI), microspheres loaded with IGF-1 or VEGF, or a combination thereof (DUAL). Myocardial injections of microspheres were performed at the time of surgery, and treatment lasted 4 weeks. Echocardiography, LV catheterization, morphometric histology and immunohistochemistry, and molecular assessment of downstream mediators [e.g. Akt, endothelial nitric oxide synthase (eNOS), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA-2)] were assessed at the end of the treatment period. Infarct sizes were 33 ± 2, 28 ± 4, 24 ± 3, and 16 ± 3% in the MI, IGF-1, VEGF, and DUAL groups, respectively. IGF-1 attenuated LV remodelling, improved LV systolic and diastolic function, increased myocyte size, and reduced apoptotic deaths, capillary loss, and indexes of inflammation. VEGF-treated animals displayed a marked myocardial neoangiogenesis that led to the formation of mature vessels if combined with IGF-1 delivery. Downstream effects of IGF-1 were principally mediated by the Akt-mTOR (mammalian target of rapamycin)-dependent pathway, and both growth factors, particularly VEGF, induced a robust and sustained increase of eNOS. IGF-1 and VEGF exerted complementary therapeutic effects in post-infarction heart failure. Biodegradable

  8. Brain aging, cognition in youth and old age and vascular disease in the Lothian Birth Cohort 1936: rationale, design and methodology of the imaging protocol. (United States)

    Wardlaw, Joanna M; Bastin, Mark E; Valdés Hernández, Maria C; Maniega, Susana Muñoz; Royle, Natalie A; Morris, Zoe; Clayden, Jonathan D; Sandeman, Elaine M; Eadie, Elizabeth; Murray, Catherine; Starr, John M; Deary, Ian J


    As the population of the world ages, age-related cognitive decline is becoming an ever-increasing problem. However, the changes in brain structure that accompany normal aging, and the role they play in cognitive decline, remain to be fully elucidated. This study aims to characterize changes in brain structure in old age, and to investigate relationships between brain aging and cognitive decline using the Lothian Birth Cohort 1936. Here, we report the rationale, design and methodology of the brain and neurovascular imaging protocol developed to study this cohort. An observational, longitudinal study of the Lothian Birth Cohort 1936, which comprises 1091 relatively healthy individuals now in their 70s and living in the Edinburgh area. They are surviving participants of the Scottish Mental Survey 1947, which involved a test of general intelligence taken at age 11 years. At age 70 years, the Lothian Birth Cohort 1936 undertook detailed cognitive, medical and genetic testing, and provided social, family, nutritional, quality of life and physical activity information. At mean age 73 years they underwent detailed brain MRI and neurovascular ultrasound imaging, repeat cognitive and other testing. The MRI protocol is designed to provide qualitative and quantitative measures of gray and white matter atrophy, severity and location of white matter lesions, enlarged perivascular spaces, brain mineral deposits, microbleeds and integrity of major white matter tracts. The neurovascular ultrasound imaging provides velocity, stenosis and intima-media thickness measurements of the carotid and vertebral arteries. This valuable imaging dataset will be used to determine which changes in brain structural parameters have the largest effects on cognitive aging. Analysis will include multimodal image analysis and multivariate techniques, such as factor analysis and structural equation modelling. Especially valuable is the ability within this sample to examine the influence that early life

  9. Uterine vascular lesions. (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash


    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.

  10. Intracavernous delivery of freshly isolated stromal vascular fraction rescues erectile function by enhancing endothelial regeneration in the streptozotocin-induced diabetic mouse. (United States)

    Ryu, Ji-Kan; Tumurbaatar, Munkhbayar; Jin, Hai-Rong; Kim, Woo Jean; Kwon, Mi-Hye; Piao, Shuguang; Choi, Min Ji; Yin, Guo Nan; Song, Kang-Moon; Kang, Yong-Jin; Koh, Young Jun; Koh, Gou Young; Suh, Jun-Kyu


    Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. To examine whether and how freshly isolated stromal vascular fraction (SVF) promotes cavernous endothelial regeneration and restores erectile function in diabetic animals. Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice. At 8 weeks after the induction of diabetes, the animals were divided into six groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 10(4) cells, 1 × 10(5) cells, or 2 × 10(5) cells/20 µL, respectively). Two weeks later, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to CD31, CD34, phosphohistone H3, phospho-endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor-A (VEGF-A). We also performed Western blot for phospho-eNOS and eNOS, and determined cyclic guanosine monophosphate (cGMP) concentration in the corpus cavernosum tissue. Significant improvement in erectile function was noted in diabetic mice treated with SVF at concentrations of 1 × 10(5) and 2 × 10(5) cells, which reached up to 82% of the control values. Local delivery of SVF significantly increased cavernous endothelial cell proliferation, eNOS phosphorylation, and cGMP expression compared with that in the untreated group and the PBS-treated diabetic group. Intracavernous injection of SVF increased cavernous VEGF-A expression and induced recruitment of CD34(+)CD31(-) progenitor cells. Some SVF underwent differentiation into cavernous endothelial cells. SVF-induced promotion of cavernous angiogenesis and erectile function was abolished in the presence of VEGF-Trap, a soluble VEGF-A neutralizing antibody. The results

  11. A methodological review of faith-based health promotion literature: advancing the science to expand delivery of diabetes education to Black Americans. (United States)

    Newlin, Kelley; Dyess, Susan MacLeod; Allard, Emily; Chase, Susan; Melkus, Gail D'Eramo


    Non-traditional avenues, such as faith-based organizations (FBOs), must be explored to expand delivery of diabetes self-management education (DSME) to benefit Black Americans with type 2 diabetes (T2D). The purpose of this study was to methodologically review the faith-based health promotion literature relevant to Blacks with T2D. A total of 14 intervention studies were identified for inclusion in the review. These studies detailed features of methods employed to affect health outcomes that DSME similarly targets. Analysis of the faith-based studies' methodological features indicated most studies used (1) collaborative research approaches, (2) pre-experimental designs, (3) similar recruitment and retention strategies, and (4) culturally sensitive, behaviorally oriented interventions with incorporation of social support to achieve positive health outcomes in Black Americans. Findings indicate FBOs may be a promising avenue for delivering DSME to Black Americans. Informed by the findings, a focused discussion on advancing the science of faith-based interventions to expand delivery of DSME to Black Americans with diabetes is provided.

  12. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2: laboratory investigation. (United States)

    Szentirmai, Oszkar; Baker, Cheryl H; Bullain, Szofia S; Lin, Ning; Takahashi, Masaya; Folkman, Judah; Mulligan, Richard C; Carter, Bob S


    Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice. Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control. Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups. These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM.

  13. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2 (United States)

    Szentirmai, Oszkar; Baker, Cheryl H.; Bullain, Szofia S.; Lin, Ning; Takahashi, Masaya; Folkman, Judah; Mulligan, Richard C.; Carter, Bob S.


    Object Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice. Methods Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control. Results Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups. Conclusions These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM. PMID:18447716


    Directory of Open Access Journals (Sweden)

    Maria Alekseyevna Cherdak


    vascular cognitive disorders and vascular dementia (VD. The heterogeneity of vascular cognitive disorders, concurrence of vascular and neurodegenerative diseases are discussed. Data from studies of specific therapy for VD are given.

  15. Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology

    Directory of Open Access Journals (Sweden)

    Srikanth Meka Venkata


    Full Text Available The aim of this research was to formulate effervescent floating drug delivery systems of theophylline using different release retarding polymers such as ethyl cellulose, Eudragit® L100, xanthan gum and polyethylene oxide (PEO N12K. Sodium bicarbonate was used as a gas generating agent. Direct compression was used to formulate floating tablets and the tablets were evaluated for their physicochemical and dissolution characteristics. PEO based formulations produced better drug release properties than other formulations. Hence, it was further optimized by central composite design. Further subjects of research were the effect of formulation variables on floating lag time and the percentage of drug released at the seventh hour (D7h. The optimum quantities of PEO and sodium bicarbonate, which had the highest desirability close to 1.0, were chosen as the statistically optimized formulation. No interaction was found between theophylline and PEO by Fourier Transformation Infrared spectroscopy (FTIR and Differential Scanning Calorimetry (DSC studies.

  16. The Application of Operations Research Methodologies to the Delivery of Care Model for Traumatic Spinal Cord Injury: The Access to Care and Timing Project (United States)

    Noonan, Vanessa K.; Soril, Lesley; Atkins, Derek; Lewis, Rachel; Santos, Argelio; Fehlings, Michael G.; Burns, Anthony S.; Singh, Anoushka


    Abstract The long-term impact of spinal cord injury (SCI) on the health care system imposes a need for greater efficiency in the use of resources and the management of care. The Access to Care and Timing (ACT) project was developed to model the health care delivery system in Canada for patients with traumatic SCI. Techniques from Operations Research, such as simulation modeling, were used to predict the impact of best practices and policy initiatives on outcomes related to both the system and patients. These methods have been used to solve similar problems in business and engineering and may offer a unique solution to the complexities encountered in SCI care delivery. Findings from various simulated scenarios, from the patients' point of injury to community re-integration, can be used to inform decisions on optimizing practice across the care continuum. This article describes specifically the methodology and implications of producing such simulations for the care of traumatic SCI in Canada. Future publications will report on specific practices pertaining to the access to specialized services and the timing of interventions evaluated using the ACT model. Results from this type of research will provide the evidence required to support clinical decision making, inform standards of care, and provide an opportunity to engage policymakers. PMID:22800432

  17. Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

    Directory of Open Access Journals (Sweden)

    Anna Poggesi


    Full Text Available Dementia is one of the most disabling conditions. Alzheimer’s disease and vascular dementia (VaD are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI. Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD.

  18. Vascular biology of preeclampsia. (United States)

    Myatt, L; Webster, R P


    Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.

  19. A novel approach for the development and optimization of self emulsifying drug delivery system using HLB and response surface methodology: application to fenofibrate encapsulation. (United States)

    Bahloul, Badr; Lassoued, Mohamed Ali; Sfar, Souad


    The aim of this work was to elaborate a novel approach for the development and optimization of self-emulsifying drug delivery system (SEDDS), using response surface methodology and hydrophilic lipophilic balance (HLB). Fenofibrate was selected as drug model. Rapid selection of excipients was operated with reference to their toxicity and capacity to solubilize the drug. A three level Box-Behnken design was used. The independent variables were (X1) surfactants/oil, (X2) cosurfactant/surfactant and (X3) percentage of cosolvent. The high and low levels of these factors were selected with reference to the experimental domain that covers an interval of HLB from 7.8 to 15. This interval of HLB is assumed to lead to oil in water emulsification and to contain the required HLB. The responses were (Y1) droplet size and (Y2) cumulative percentage drug released in 20 mn.Various response surface graphs were constructed to understand the effects of different factor level combinations. The optimized SEDDS with predicted drug release 83.6%, and droplet size 137 nm was prepared; the experimental values were in close agreement. The required HLB was 9.85. Optimized SEDDS showed significant increase in dissolution rate compared to conventional prepared gelatin capsules. In conclusion, this paper demonstrated the reliability, rapidity, and robustness of the approach. Copyright © 2014. Published by Elsevier B.V.

  20. Vascular Cures (United States)

    ... is the first national program to bring the power of the patient to vascular research and care. ... Our recent national Vascular Research Summit brought together leaders from 31 institutions to generate collaborative projects for ...

  1. The pathobiology of vascular dementia. (United States)

    Iadecola, Costantino


    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Enzymatic in situ formed hydrogel from gelatin-tyramine and chitosan-4-hydroxylphenyl acetamide for the co-delivery of human adipose-derived stem cells and platelet-derived growth factor towards vascularization. (United States)

    Linh, Nguyen Thuy Ba; Abueva, Celine D G; Lee, Byong-Taek


    An injectable, in situ forming hydrogel system capable of co-delivering human adipose-derived stem cells (hADSC) and platelet-derived growth factor (PDGF) was investigated as a new system for tissue engineering, envisaged to support vascularization. The system consists of tyramine-conjugated gelatin and hydroxyphenyl acetamide chitosan derivative. Both are soluble and stable at physiologic conditions, which is a key factor for retaining viable cells and active growth factor. In situ gelation involved enzymatic crosslinking using horseradish peroxidase as a catalyst and hydrogen peroxide as an oxidant. Gel formation occurred within 30-90 s by controlling the concentration of polymers. PDGF release showed adequate release kinetics within the intended period of time and hADSC showed good compatibility with the hydrogel formulation based on the in vitro assay and subcutaneous implantation into BALB/c-nu/nu nude female mice. Immunohistochemical analysis confirmed viability of delivered hADSC. Histological analysis showed no immune reaction and confirmed blood vessel formation. The results implicate the hydrogel as a promising delivery vehicle or carrier of both cell and growth factor, which support vascularization for tissue engineering applications.

  3. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van


    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  4. A nanomedicine approach to effectively inhibit contracture during bladder acellular matrix allograft-induced bladder regeneration by sustained delivery of vascular endothelial growth factor. (United States)

    Xiong, Qianwei; Lin, Houwei; Hua, Xiaolin; Liu, Li; Sun, Ping; Zhao, Zhen; Shen, Xiaowei; Cui, Daxiang; Xu, Maosheng; Chen, Fang; Geng, Hongquan


    Macroscopic evidence of contracture has been identified as a major issue during the regeneration process. We hypothesize that lack of angiogenesis is the primary cause of contracture and explore a nanomedicine approach to achieve sustained release of vascular endothelial growth factor (VEGF) to stimulate angiogenesis. We evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for long-term (3 months) sustained release of VEGF in bladder acellular matrix allografts (BAMA) in a swine model. We anticipate that the sustained release of VEGF could stimulate angiogenesis along the regeneration process and thereby inhibit contracture. Bladder was replaced with BAMA (5×5 cm), modified with PLGA NPs encapsulated with VEGF in a pig model. The time points chosen for sampling were 1, 2, 4, and 12 weeks. The regenerated areas were then measured to obtain the contracture rate, and the extent of revascularization was calculated using histological and morphological features. In the control group of animals, the bladder was replaced with only BAMA. The in vivo release of VEGF was evident for ∼3 months, achieving the goal of long-acting sustained release, and successfully promoted the regeneration of blood vessels and smooth muscle fibers. In addition, less collagen deposition was observed in the experimental group compared with control. Most importantly, the inhibition of contracture was highly significant, and the ultimate contracture rate decreased by ∼57% in the experimental group compared with control. In isolated strips analysis, there were no significant differences between BAMA-regenerated (either VEGF added or not) and autogenous bladder. BAMA modified with VEGF-loaded PLGA-NPs can sustainably release VEGF in vivo (>3 months) to stimulate angiogenesis leading to the inhibition of contracture. This is the first study to report a viable nanomedicine-based strategy to overcome contracture during bladder regeneration induced by BAMA. Furthermore

  5. Vascular ring

    DEFF Research Database (Denmark)

    Schmidt, Anne Mette S; Larsen, Signe H; Hjortdal, Vibeke E


    BACKGROUND: Vascular ring is a rare cause of recurrent respiratory infections, dysphagia and stridor. Surgical repair is considered safe but the long-term outcomes are unclear. The purpose of this study was to investigate the mortality and morbidity following vascular ring surgery in a single...... age of 1.4 years (range 0.008-64 years) were operated for vascular ring. Median follow-up was 6.8 years (range 2.4-34 years). Presenting symptoms were stridor (52%), dysphagia or vomiting (52%) and recurrent respiratory infections (48%). There were no early or late deaths. Three months postoperatively...

  6. Vascular anomalies

    Directory of Open Access Journals (Sweden)

    Murthy Jyotsna


    Full Text Available Management of vascular anomalies is an emerging multidisciplinary, super-specialisation field involving several surgical, medical and radiological specialties. Over the years, development in this field has been limited because of complex nomenclature and lack of consensus on the best practice for treatment of some of the more complex vascular anomalies. It was only in 1996 that the International Society of the Study of Vascular Anomalies defined nomenclature for the anomalies and gave clear guidelines on management, allowing for improved clinical practices. As in all fields of clinical medicine, the correct diagnosis of the vascular anomalies is essential to choose the appropriate treatment. This paper gives clear guidelines for diagnosis, understanding of the anomalies and discusses their management.

  7. Vascular Dementia


    Maria Alekseyevna Cherdak; O V Uspenskaya


    This is the author accepted manuscript. The final version is available from Elsevier via Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the e...

  8. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar


    Full Text Available Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

  9. Vascular Access Procedures (United States)

    ... News Physician Resources Professions Site Index A-Z Vascular Access Procedures A vascular access procedure inserts a flexible, ... the limitations of Vascular Access Procedures? What are Vascular Access Procedures? A vascular access procedure involves the insertion ...

  10. Vascular Access for Hemodialysis (United States)

    ... Adequacy Eating & Nutrition for Hemodialysis Vascular Access for Hemodialysis What is a vascular access? A vascular access ... Set Up the Vascular Access Well before Starting Hemodialysis Patients should set up a vascular access well ...

  11. What Is Vascular Disease? (United States)

    ... Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of the blood ... Privacy Policy × Your ticket for the: What Is Vascular Disease? Title What Is Vascular Disease? USD Close Print

  12. Vascular dementia. (United States)

    O'Brien, John T; Thomas, Alan


    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment targets. Although there is an established relation between vascular and degenerative Alzheimer's pathology, the mechanistic link between the two has not yet been identified. This Series paper critiques some of the key areas and controversies, summarises treatment trials so far, and makes suggestions for what progress is needed to advance our understanding of pathogenesis and thus maximise opportunities for the search for new and effective management approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. [Vascular trauma]. (United States)

    Furuya, T; Nobori, M; Tanaka, N


    Vascular trauma is essentially acute arterial obstruction, often combined with hemorrhage, fracture, and infection. It can be both life-threatening and limb-threatening and needs an emergency operation. In vascular trauma patient, multiple fracture and organ injury, such as brain, lung, liver, spleen, kidney, or gastrointestinal tract should be evaluated to decide treatment priority. When the pulse distal from the injured site is absent or diminished, vascular trauma is most likely and reconstruction should be accomplished within "the golden time (6-8 hours)". Intimal damage followed by platelet aggregation and thrombus formation will necessitate resection and repair of the site instead of simple thrombectomy. Although autogenous vein is the first choice, artificial graft can be implanted for short segment in non-infected field.

  14. Contemporary vascular smartphone medical applications. (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W


    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.


    African Journals Online (AJOL)

    Venous thromboembolism (VTE) is a complex and serious condition encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), usually in the lower extremities.1,2. Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are ...

  16. Angioembolisation in vaginal vascular malformation.

    Directory of Open Access Journals (Sweden)

    Srivastava D


    Full Text Available Vaginal arteriovenous malformations are rare entities and their most common presentation is vaginal haemorrhage. This case report describes a 22-year-old woman who presented at 20 weeks of gestation with slow growing soft and tender swelling at anterior vaginal wall. Diagnosis was confirmed as vaginal vascular malformation on contrast enhanced magnetic resonance imaging. The mass did not subside after delivery and patient developed dyspareunia. It was successfully treated by angioembolisation using polyvinyl alcohol particles. Angioembolisation being safe and effective should be the treatment of first choice for symptomatic vaginal vascular malformation.

  17. Optimization of chlorpheniramine maleate (CPM delivery by response surface methodology – four component modeling using various response times and concentrations of chitosan-alanine, glutaraldehyde and CPM

    Directory of Open Access Journals (Sweden)


    Full Text Available The aim of the current study was to investigate the effects of formulation variables on the release of drug and to optimize the formulation of chitosan-alanine beads loaded with chlorpheniramine maleate (CPM for controlled release using response surface methodology (RSM. Drug loaded beads of chitosan-alanine were prepared and crosslinked by using glutaraldehyde as crosslinker. The release behavior of drug was affected by preparation variables. A central composite design was used to evaluate and optimize the effect of preparation variables; chitosan concentration (X1, percentage of crosslinker (X2, concentration of drug (X3 and release time (X4 on the cumulative amount of drug release, Y in solutions of pH = 2.0 and pH = 7.4, respectively. The influence of each parameter was studied by factorial design analysis. Analysis of variance (ANOVA was also used to evaluate the validity of the model. The statistical parameters reveal strong evidence that the constructed models for drug release in pH = 2 and pH = 7.4 are reliable.

  18. Subclinical hypothyroidism after vascular complicated pregnancy. (United States)

    van der Zanden, Moniek; Hop-de Groot, Rianne J; Sweep, Fred C G J; Ross, H Alec; den Heijer, Martin; Spaanderman, Marc E A


    Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions. In 372 women with a history of vascular complicated pregnancy, we assessed thyroid function. Subclinical hypothyroidism was diagnosed in 73/372 women (19.6%). It occurred more often when pregnancy ended before 32 weeks of gestation (p = 0.008). In this cohort, subclinical hypothyroidism is more common after very preterm delivery. It may contribute to the elevated risk of remote cardiovascular disease.

  19. Silk Biomaterials with Vascularization Capacity. (United States)

    Han, Hongyan; Ning, Hongyan; Liu, Shanshan; Lu, Qiang; Fan, Zhihai; Lu, Haijun; Lu, Guozhong; Kaplan, David L


    Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver or bone. The immobilization or delivery of growth factors has been explored to improve vascularization capacity of tissue engineered constructs, however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications such as immunological responses and cancer. Here, a new method of preparing water-insoluble silk protein scaffolds with vascularization capacity using an all aqueous process is reported. Acid was added temporally to tune the self-assembly of silk in lyophilization process, resulting in water insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk-based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.

  20. Plant Vascular Biology 2013: vascular trafficking. (United States)

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä


    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland ( The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  1. Tourism Methodologies

    DEFF Research Database (Denmark)

    This volume offers methodological discussions within the multidisciplinary field of tourism and shows how tourism researchers develop and apply new tourism methodologies. The book is presented as an anthology, giving voice to many diverse researchers who reflect on tourism methodology in differen...... codings and analysis, and tapping into the global network of social media.......This volume offers methodological discussions within the multidisciplinary field of tourism and shows how tourism researchers develop and apply new tourism methodologies. The book is presented as an anthology, giving voice to many diverse researchers who reflect on tourism methodology in different...... in interview and field work situations, and how do we engage with the performative aspects of tourism as a field of study? The book acknowledges that research is also performance and that it constitutes an aspect of intervention in the situations and contexts it is trying to explore. This is an issue dealt...

  2. Nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery - properties, methodologies and applications; Plataformas bio(muco) adesivas polimericas baseadas em nanotecnologia para liberacao controlada de farmacos - propriedades, metodologias e aplicacoes

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Flavia Chiva; Chorilli, Marlus; Gremiao, Maria Palmira Daflon, E-mail: [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Fac. de Ciencias Farmaceuticas. Dept. de Farmacos e Medicamentos


    Studies using bio(muco)adhesive drug delivery systems have recently gained great interest, which can promote drug targeting and more specific contact of the drug delivery system with the various absorptive membranes of the body. This technological platform associated with nanotechnology offers potential for controlling drug delivery; therefore, they are excellent strategies to increase the bioavailability of drugs. The objective of this work was to study nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery, highlighting their properties, how the bio(muco)adhesion can be measured and their potential applications for different routes of administration. (author)

  3. Bioprinting for vascular and vascularized tissue biofabrication. (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T


    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  4. Tourism Methodologies

    DEFF Research Database (Denmark)

    This volume offers methodological discussions within the multidisciplinary field of tourism and shows how tourism researchers develop and apply new tourism methodologies. The book is presented as an anthology, giving voice to many diverse researchers who reflect on tourism methodology in different...... ways. Several contributions draw on a critical perspective that pushes the boundaries of traditional methods and techniques for studying tourists and their experiences. In particular, the traditional qualitative interview is challenged, not only regarding the typical questions asked, but also regarding...

  5. Collagen vascular disease (United States)

    ... page: // Collagen vascular disease To use the sharing features on this page, ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific conditions ...

  6. Tourism Methodologies

    DEFF Research Database (Denmark)

    This volume offers methodological discussions within the multidisciplinary field of tourism and shows how tourism researchers develop and apply new tourism methodologies. The book is presented as an anthology, giving voice to many diverse researchers who reflect on tourism methodology in different...... in interview and field work situations, and how do we engage with the performative aspects of tourism as a field of study? The book acknowledges that research is also performance and that it constitutes an aspect of intervention in the situations and contexts it is trying to explore. This is an issue dealt...

  7. Epigenetic Diabetic Vascular Complications

    Directory of Open Access Journals (Sweden)

    Ali Ahmadzadeh-Amiri


    Full Text Available Diabetic vascular complications (DVC influence several vital organ systems including cardiovascular, renal, ocular and nervous systems making it a major public health problem. Although extensive researches were performed in this field, the exact mechanisms responsible for these organ damages in diabetes remain obscure. Several metabolic disturbances have been involved in its complication and change in genes associated with these pathways occurred. Gene expression to produce a biologically active protein can be controlled by transcriptional and translational alteration on the head of genes without change in nucleotide composition. These epigenetic adjustments are steady, but possibly reversible and can be transmitted to future generation. Gene expression can be regulated by three epigenetic mechanisms including DNA methylation, histone modifications and noncoding microRNAs (miRNAs activity. Epigenetic studies must be directed to better realize the role of epigenetic changes to the etiology of DVC and knowledge of epigenetic would play a pivotal role in the application of individualized medicine. Application and development of high technology sequencing combined with more sensitive and advanced methodologies for epigenome studying help to determine specific epigenetic events that stimulate gene responses in patients with diabetes mellitus.

  8. Quantifying the bioadhesive properties of surface-modified polyurethane-urea nanoparticles in the vascular network. (United States)

    Melgar-Lesmes, Pedro; Morral-Ruíz, Genoveva; Solans, Conxita; García-Celma, María José


    Nanomedicine research is currently requiring new standard methods to quantify the biocompatibility and bioadhesivity of emerging biomaterials designed to be used in contact with blood or soft tissues. In this study, we used biotinylated polyurethane-urea nanoparticles as a model to examine the applicabitility of an adapted hemagglutination assay to quantify the bioadhesive potential of these nanoparticles to red blood cells and, in turn, to extrapolate this data to vascular endothelial cells. We demonstrated that biotinylated nanoparticles adsorb to human erythrocytes and preferentially gather in erythrocyte contact areas. Moreover, these nanoparticles promoted a higher percentage of pig and human erythrocyte agglutination than naked polyurethane-urea nanoparticles in a biotin concentration-dependent manner. Conversely, pegylated nanoparticles were used as a negative control of the technique thus showing decreasing hemagglutination values as compared to naked nanoparticles until a minimum threshold. Furthermore, hemagglutination assay demonstrated an excellent positive correlation with bioadhesion quantification in human endothelial cells and the endothelial layer of pig aorta thus validating the hemagglutination assay described here as a useful method for predicting nanoparticle bioadhesivity to vascular endothelium. Therefore, the methodology described here is a versatile and straightforward method that allows evaluating the bioadhesive features of surface-modified polyurethane-urea nanoparticles in contact with blood and the vascular network and appears as a powerful tool to better design any drug delivery systems or implantable devices for biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Tourism Methodologies

    DEFF Research Database (Denmark)

    This volume offers methodological discussions within the multidisciplinary field of tourism and shows how tourism researchers develop and apply new tourism methodologies. The book is presented as an anthology, giving voice to many diverse researchers who reflect on tourism methodology in different...... in interview and field work situations, and how do we engage with the performative aspects of tourism as a field of study? The book acknowledges that research is also performance and that it constitutes an aspect of intervention in the situations and contexts it is trying to explore. This is an issue dealt...... with in different ways, depending on the ontological and epistemological stands of the researcher. The book suggests new methods and approaches, with innovative ways of collecting and creating empirical materials, by expanding the approaches to tried and tested methods, including digital innovations, digital...

  10. Endothelial microparticles: Sophisticated vesicles modulating vascular function (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R


    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  11. On methodology

    DEFF Research Database (Denmark)

    Cheesman, Robin; Faraone, Roque


    This is an English version of the methodology chapter in the authors' book "El caso Berríos: Estudio sobre información errónea, desinformación y manipulación de la opinión pública".......This is an English version of the methodology chapter in the authors' book "El caso Berríos: Estudio sobre información errónea, desinformación y manipulación de la opinión pública"....

  12. Pressurized vascular systems for self-healing materials. (United States)

    Hamilton, A R; Sottos, N R; White, S R


    An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen.

  13. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt


    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...

  14. After Delivery (United States)

    ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... A Listen En Español After Delivery After your baby arrives, your body begins to recover from the ...

  15. Forceps Delivery (United States)

    ... 2015. Related Signs of labor Forceps delivery About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  16. Methodological guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Halsnaes, K.; Callaway, J.M.; Meyer, H.J.


    The guideline document establishes a general overview of the main components of climate change mitigation assessment. This includes an outline of key economic concepts, scenario structure, common assumptions, modelling tools and country study assumptions. The guidelines are supported by Handbook Reports that contain more detailed specifications of calculation standards, input assumptions and available tools. The major objectives of the project have been provided a methodology, an implementing framework and a reporting system which countries can follow in meeting their future reporting obligations under the FCCC and for GEF enabling activities. The project builds upon the methodology development and application in the UNEP National Abatement Coasting Studies (UNEP, 1994a). The various elements provide countries with a road map for conducting climate change mitigation studies and submitting national reports as required by the FCCC. (au) 121 refs.

  17. Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos syndrome. (United States)

    Murray, Mitzi L; Pepin, Melanie; Peterson, Suzanne; Byers, Peter H


    The purpose of this study was to characterize the nature and magnitude of pregnancy risks in women with vascular Ehlers-Danlos syndrome. Pregnancy-related death rate was determined by a review of pedigrees of families with vascular Ehlers-Danlos syndrome. Maternal morbidity was characterized through semistructured interviews with women with vascular Ehlers-Danlos syndrome or their next of kin. Pregnancy-related deaths occurred in 30 of 565 deliveries (5.3%). There was no difference in Kaplan-Meier survival curves between parous versus nulliparous women with vascular Ehlers-Danlos syndrome. Interviews with 39 women indicated that 46% of deliveries were uncomplicated. The most common pregnancy-related complications were third-/fourth-degree lacerations (20%) and preterm delivery (19%). Life-threatening complications occurred in 14.5% of deliveries and included arterial dissection/rupture (9.2%), uterine rupture (2.6%), and surgical complications (2.6%). There were 5 maternal deaths in 76 deliveries (6.5%). The risk of pregnancy-related complications is increased in women with vascular Ehlers-Danlos syndrome compared with the general population; however, survival data indicate that pregnancy does not appear to affect overall mortality compared with nulliparous women with vascular Ehlers-Danlos syndrome. The data were insufficient to determine whether mode or timing of delivery influenced risk of complications. Women with vascular Ehlers-Danlos syndrome should be engaged in a shared decision-making process when contemplating pregnancy and pregnancy management.

  18. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt


    years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...

  19. A novel needleless liquid jet injection methodology for improving direct cardiac gene delivery: An optimization of parameters, AAV mediated therapy and investigation of host responses in ischemic heart failure (United States)

    Fargnoli, Anthony Samuel

    Heart disease remains the leading cause of mortality and morbidity worldwide, with 22 million new patients diagnosed annually. Essentially, all present therapies have significant cost burden to the healthcare system, yet fail to increase survival rates. One key employed strategy is the genetic reprogramming of cells to increase contractility via gene therapy, which has advanced to Phase IIb Clinical Trials for advanced heart failure patients. It has been argued that the most significant barrier preventing FDA approval are resolving problems with safe, efficient myocardial delivery, whereby direct injection in the infarct and remote tissue areas is not clinically feasible. Here, we aim to: (1) Improve direct cardiac gene delivery through the development of a novel liquid jet device approach (2) Compare the new method against traditional IM injection with two different vector constructions and evaluate outcome (3) Evaluate the host response resulting from both modes of direct cardiac injection, then advance a drug/gene combination with controlled release nanoparticle formulations.

  20. Vascular cognitive impairment and vascular dementia

    Directory of Open Access Journals (Sweden)

    Klavdija Ovčar


    Full Text Available In the developed world, five to ten percent of people older than 65 years have dementia. One fifth of dementia etiologies are due to vascular brain lesions (VaD – vascular dementia. A milder form is called vascular cognitive impairment (VCI. The main clinical criteria for VaD are: 1. cognitive decline verified with standardized cognitive test/scale, 2. evidence of the associated vascular brain lesion, 3. excluded reversible causes of cognitive decline. The main risk factors for VaD are age, atherosclerosis, diabetes and hypertension. They play a key role in pathogenesis of the cognitive impairment. Depending on the damaged brain region, different cognitive domains may be affected with or without other neurological signs. These diversities in the clinical picture challenge the correct diagnosis. Unique feature of VaD is its progression, which can be stopped, if patients receive an appropriate treatment.The treatment of VCI and VaD symptoms is similar to that in Alzheimer’s disease. More importantly, VCI may be slowed down or even stopped with proper secondary stroke prevention and good rehabilitation. The most efficient is primary stroke prevention with healthy lifestyle and treatment of acquired risk factors.

  1. Vascular disease burden in Indian subjects with vascular dementia. (United States)

    Chandra, Mina; Anand, Kuljeet Singh


    Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia. To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia. In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis. Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001). People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.

  2. Vascular remodelling in asthma. (United States)

    Walters, Eugene Haydn; Soltani, Amir; Reid, David William; Ward, Chris


    We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

  3. Enhancing engineered vascular networks in vitro and in vivo: The effects of IGF1 on vascular development and durability. (United States)

    Friedrich, Claudia C; Lin, Yunfeng; Krannich, Alexander; Wu, Yinan; Vacanti, Joseph P; Neville, Craig M


    Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin-like growth factor 1 (IGF1) would enhance the engineering of capillary-like vasculature. The impact of IGF1 upon vasculogenesis was examined in in vitro cultures for a period of up to 40 days and as subcutaneous implants within immunodeficient mice. Co-cultures of human umbilical vein endothelial cells and human bone marrow-derived mesenchymal stem cells in collagen-fibronectin hydrogels were supplemented with either recombinant IGF1 protein or genetically engineered cells to provide sustained IGF1. Morphometric analysis was performed on the vascular networks that formed in four concentrations of IGF1. IGF1 supplementation significantly enhanced de novo vasculogenesis both in vitro and in vivo. Effects were long-term as they lasted the duration of the study period, and included network density, vessel length, and diameter. Bifurcation density was not affected. However, the highest concentrations of IGF1 tested were either ineffective or even deleterious. Sustained IGF1 delivery was required in vivo as the inclusion of recombinant IGF1 protein had minimal impact. IGF1 supplementation can be used to produce neovasculature with significantly enhanced network density and durability. Its use is a promising methodology for engineering de novo vasculature to support regeneration of functional tissue. © 2017 John Wiley & Sons Ltd.

  4. Methodological advances

    Directory of Open Access Journals (Sweden)

    Lebreton, J.-D.


    Full Text Available The study of population dynamics has long depended on methodological progress. Among many striking examples, continuous time models for populations structured in age (Sharpe & Lotka, 1911 were made possible by progress in the mathematics of integral equations. Therefore the relationship between population ecology and mathematical and statistical modelling in the broad sense raises a challenge in interdisciplinary research. After the impetus given in particular by Seber (1982, the regular biennial EURING conferences became a major vehicle to achieve this goal. It is thus not surprising that EURING 2003 included a session entitled “Methodological advances”. Even if at risk of heterogeneity in the topics covered and of overlap with other sessions, such a session was a logical way of ensuring that recent and exciting new developments were made available for discussion, further development by biometricians and use by population biologists. The topics covered included several to which full sessions were devoted at EURING 2000 (Anderson, 2001 such as: individual covariates, Bayesian methods, and multi–state models. Some other topics (heterogeneity models, exploited populations and integrated modelling had been addressed by contributed talks or posters. Their presence among “methodological advances”, as well as in other sessions of EURING 2003, was intended as a response to their rapid development and potential relevance to biological questions. We briefly review all talks here, including those not published in the proceedings. In the plenary talk, Pradel et al. (in prep. developed GOF tests for multi–state models. Until recently, the only goodness–of–fit procedures for multistate models were ad hoc, and non optimal, involving use of standard tests for single state models (Lebreton & Pradel, 2002. Pradel et al. (2003 proposed a general approach based in particular on mixtures of multinomial distributions. Pradel et al. (in prep. showed

  5. Forceps delivery at the University College Hospital, Ibadan, Nigeria ...

    African Journals Online (AJOL)

    The incidence of forceps delivery has reduced in Nigeria and in the world in general. Some Obstetricians have not been trained in its use and lack the skill. Objective: To determine the outcome of forceps delivery at this centre. Methodology: A retrospective analysis of all forceps delivery done at this centre between the 1st of ...

  6. Understanding Vascular Endothelium


    Gimbrone, Michael A.


    Understanding Vascular Endothelium : Nature’s Container for Blood The entire cardiovascular system, from the chambers of the heart to the smallest capillaries of peripheral tissues, is lined by a single-cell-thick continuous layer—the vascular endothelium. For many years, this gossamer membrane was thought to function largely as an inert barrier, passively separating the reactive components of the circulating blood from the cells and connective tissue matrix of the various organs of the body....

  7. Hypercholesterolaemia and vascular dementia


    Appleton, Jason P.; Scutt, Polly; Sprigg, Nikola; Bath, Philip M.


    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors–diabetes, hypercholesterolaemia, hypertension and smoking–are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet no...

  8. Testing methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M.A.


    Several methodologies are available for screening human populations for exposure to ionizing radiation. Of these, aberration frequency determined in peripheral blood lymphocytes is the best developed. Individual exposures to large doses can easily be quantitated, and population exposures to occupational levels can be detected. However, determination of exposures to the very low doses anticipated from a low-level radioactive waste disposal site is more problematical. Aberrations occur spontaneously, without known cause. Exposure to radiation induces no new or novel types, but only increases their frequency. The limitations of chromosomal aberration dosimetry for detecting low level radiation exposures lie mainly in the statistical signal to noise'' problem, the distribution of aberrations among cells and among individuals, and the possible induction of aberrations by other environmental occupational or medical exposures. However, certain features of the human peripheral lymphocyte-chromosomal aberration system make it useful in screening for certain types of exposures. Future technical developments may make chromosomal aberration dosimetry more useful for low-level radiation exposures. Other methods, measuring gene mutations or even minute changes on the DNA level, while presently less will developed techniques, may eventually become even more practical and sensitive assays for human radiation exposure. 15 refs.

  9. Antioxidants and vascular health. (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto


    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  10. Vascularized epiphyseal transplant. (United States)

    Innocenti, Marco; Delcroix, Luca; Romano, G Federico; Capanna, Rodolfo


    In skeletally immature patients, the transfer of vascularized epiphysis along with a variable amount of adjoining diaphysis may provide the potential for growth of such a graft, preventing future limb length discrepancy. This article describes the authors' experience with the vascularized transfer of the proximal fibular epiphysis in the reconstruction of large bone defects including the epiphysis in a series of 27 patients ranging in age from 2 to 11 years. The follow-up, ranging from 2 to 14 years, has been long enough to allow some evaluation of the validity, indications, and limits of this reconstructive option.

  11. Vascular Neurology Nurse Practitioner Provision of Telemedicine Consultations

    Directory of Open Access Journals (Sweden)

    Bart M. Demaerschalk


    Full Text Available Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP in the delivery of telemedicine consultations in partnership with a vascular neurologist. Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated. Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was 53.2±9.0 minutes, which included the vascular neurologist supervisory evaluation time of 12.0±9.6 minutes. Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider.

  12. Disruptive technological advances in vascular access for dialysis: an overview. (United States)

    Yeo, Wee-Song; Ng, Qin Xiang


    End-stage kidney disease (ESKD), one of the most prevalent diseases in the world and with increasing incidence, is associated with significant morbidity and mortality. Current available modes of renal replacement therapy (RRT) include dialysis and renal transplantation. Though renal transplantation is the preferred and ideal mode of RRT, this modality may not be available to all patients with ESKD. Moreover, renal transplant recipients are constantly at risk of complications associated with immunosuppression and immunosuppressant use, and posttransplant lymphoproliferative disorder. Dialysis may be the only available modality in certain patients. However, dialysis has its limitations, which include issues associated with lack of vascular access, risks of infections and vascular thrombosis, decreased quality of life, and absence of biosynthetic functions of the kidney. In particular, the creation and maintenance of hemodialysis vascular access in children poses a unique set of challenges to the pediatric nephrologist owing to the smaller vessel diameters and vascular hyperreactivity compared with adult patients. Vascular access issues continue to be one of the major limiting factors prohibiting the delivery of adequate dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review aims to provide a critical overview of disruptive technological advances and innovations for vascular access. Novel strategies in preventing neointimal hyperplasia, novel bioengineered products, grafts and devices for vascular access will be discussed. The potential impact of these solutions on improving the morbidity encountered by dialysis patients will also be examined.

  13. in silico Vascular Modeling for Personalized Nanoparticle Delivery (United States)


    Eq.(9)); and a Robin -type boundary condition (Eq.(10)), a combination of the Dirichlet and Neumann conditions, was prescribed at the rigid wall...Sciences 1971;177(1046): 109-33. 42. Feldman CL, Ilegbusi OJ, Hu Z, Nesto R, Waxman S, Stone PH. Determination of in vivo velocity and endothelial

  14. Spinal Anaesthesia for Cesarean Section in a Patient with Vascular Type Ehlers-Danlos Syndrome

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Carness


    Full Text Available We report the administration of spinal anaesthesia for cesarean delivery in a parturient with vascular Ehlers-Danlos syndrome. Parturients who genetically inherit this disorder are at risk for significant morbidity and mortality. Risks during pregnancy include premature labor, uterine prolapse, and uterine rupture. Additionally, such laboring parturients are at increased risk of hemodynamic volatility, vascular stress, and severe postpartum hemorrhage. Instrumented delivery and cesarean delivery bring additional risks. Nonpregnancy-related complications include excessive bleeding, intestinal rupture, cardiac valvular dysfunction, and arterial dissection. Despite the complexity of this condition, literature focusing on specific intraoperative anaesthetic management is sparse.

  15. Spanish Clinical Guidelines on Vascular Access for Haemodialysis. (United States)

    Ibeas, José; Roca-Tey, Ramon; Vallespín, Joaquín; Moreno, Teresa; Moñux, Guillermo; Martí-Monrós, Anna; Pozo, José Luis Del; Gruss, Enrique; Arellano, Manel Ramírez de; Fontseré, Néstor; Arenas, María Dolores; Merino, José Luis; García-Revillo, José; Caro, Pilar; López-Espada, Cristina; Giménez-Gaibar, Antonio; Fernández-Lucas, Milagros; Valdés, Pablo; Fernández-Quesada, Fidel; de la Fuente, Natalia; Hernán, David; Arribas, Patricia; de la Nieta, María Dolores Sánchez; Martínez, María Teresa; Barba, Ángel


    Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Hypercholesterolaemia and vascular dementia. (United States)

    Appleton, Jason P; Scutt, Polly; Sprigg, Nikola; Bath, Philip M


    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors-diabetes, hypercholesterolaemia, hypertension and smoking-are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here. © 2017 The Author(s).

  17. Depression in vascular dementia.

    NARCIS (Netherlands)

    Naarding, P.; Koning, I. de; Kooten, F. van; Dippel, D.W.; Janzing, J.G.E.; Mast, R.C. van der; Koudstaal, P.J.


    OBJECTIVE: To study the presence of different dimensions of depression in subjects with vascular dementia. BACKGROUND: After a stroke, cognitive, affective and behavioural disturbances are common. It has been suggested that the nature of affective symptomatology can help to differentiate organic

  18. Vascular management in rotationplasty. (United States)

    Mahoney, Craig R; Hartman, Curtis W; Simon, Pamela J; Baxter, B Timothy; Neff, James R


    The Van Nes rotationplasty is a useful limb-preserving procedure for skeletally immature patients with distal femoral or proximal tibial malignancy. The vascular supply to the lower limb either must be maintained and rotated or transected and reanastomosed. We asked whether there would be any difference in the ankle brachial index or complication rate for the two methods of vascular management. Vessels were resected with the tumor in seven patients and preserved and rotated in nine patients. One amputation occurred in the group in which the vessels were preserved. Four patients died secondary to metastatic disease diagnosed preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear similar using both methods of vascular management and one should not hesitate to perform an en bloc resection when there is a question of vascular involvement.

  19. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav


    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  20. Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders. (United States)

    Ringvold, H C; Khalil, R A


    Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca2+-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca2+-dependent α, β, and γ, novel Ca2+-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

  1. Tissue Bioeffects during Ultrasound-mediated Drug Delivery (United States)

    Sutton, Jonathan

    Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.

  2. A protocol for sampling vascular epiphyte richness and abundance

    NARCIS (Netherlands)

    Wolf, J.H.D.; Gradstein, S.R.; Nadkarni, N.M.


    The sampling of epiphytes is fraught with methodological difficulties. We present a protocol to sample and analyse vascular epiphyte richness and abundance in forests of different structure (SVERA). Epiphyte abundance is estimated as biomass by recording the number of plant components in a range of

  3. Vascular manifestations of Behcet's disease

    Directory of Open Access Journals (Sweden)

    Regina Georgiyeva Goloeva


    Conclusion. Vascular disorders in BD were diagnosed in one fourth of the patients, mainly in young male patients. Severe thromboses with the development of chronic venous insignificance, Budd-Chiari syndrome, pulmonary and iliac artery aneurysms, and arterial thromboses were observed in male patients only. Vascular events were associated with erythema nodosum and epididymitis; in these concomitances, the vascular risk was substantially increased. Vascular death rates were 2,2%.

  4. Safety, Healing, and Efficacy of Vascular Prostheses Coated with Hydroxypropyl-[beta]-cyclodextrin Polymer: Experimental In Vitro and Animal Studies

    National Research Council Canada - National Science Library

    Jean-Baptiste, E; Blanchemain, N; Martel, B; Neut, C; Hildebrand, H.F; Haulon, S


    Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-[beta]-cyclodextrin (HP[beta]CD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules...

  5. Safety, healing, and efficacy of vascular prostheses coated with hydroxypropyl-β-cyclodextrin polymer: experimental in vitro and animal studies

    National Research Council Canada - National Science Library

    Jean-Baptiste, E; Blanchemain, N; Martel, B; Neut, C; Hildebrand, H F; Haulon, S


    Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-β-cyclodextrin (HPβCD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules...

  6. Epidemiology, diagnostics and treatment of vascular tumours and malformations. (United States)

    Wójcicki, Piotr; Wójcicka, Karolina


    Vascular tumours and vascular malformations are common vasculose anomalies characteristic for dissimilar clinical course, specific biological as well as immune cytological and histological properties. Vascular lesions classification system and their detailed division into groups and subgroups were elaborated and implemented in Rome, in 1996, during meeting of the International Society for the Study of Vascular Anomalies (ISSVA). It was based on modification of an earlier going division by Mullikien and Głowacki from 1982. Infantile hemangiomas are the most numerous group of benign tumours of mesenchymal origin. Vascular malformations appear definitely less often. They are composed of normal endothelium lined displastic vessels which originate from vascular tissue abnormal morphogenesis. In contrast, in hemangiomas, at the proliferation stage, increased, multiplication of endothelial cells is observed as well as of fibroblasts, mastocytes and macrophages. Infantile hemangiomas are usually not present at the moment of birth and white chloasma with superficial teleangiectasis appears which increases within 3-4 weeks and gets bright red colour and reveal very characteristic clinical course basing on intensive growth period and involution long process. Vascular malformations are observed most often at the delivery moment or they may appear at an early childhood. They enlarge proportionally along with the child's growth and their sudden expansion may be triggered by an infection, hormonal changes or trauma. Contrary to hemangiomas, they do not subside spontaneously and their abrupt increase may result in impairment or deformation of important anatomical structures. Infantile hemangiomas and vascular malformations require different and individual treatments which are often multi-stage procedures carried on in specialistic centres of plastic surgery, vascular surgery or maxillofacial surgery.

  7. Engineering vascularized skeletal muscle tissue

    NARCIS (Netherlands)

    Levenberg, Shulamit; Rouwkema, Jeroen; Macdonald, Mara; Garfein, Evan S.; Kohane, Daniel S.; Darland, Diane C.; Marini, Robert; van Blitterswijk, Clemens; Mulligan, Richard C.; D'Amore, Patricia A.; Langer, Robert


    One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe

  8. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression (United States)

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.


    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  9. Brain Vascular Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Bàrbara Laviña


    Full Text Available Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain during development and adulthood; as well as to observe the vascular responses in disease situations in vivo. This review offers a concise summary and brief historical reference of different imaging techniques and how these tools can be applied to study the brain vasculature and the blood-brain barrier integrity in both healthy and disease states. Moreover, it offers an overview on available transgenic animal models to study vascular biology and a description of useful online brain atlases.

  10. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao


    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  11. Pathophysiology of vascular dementia

    Directory of Open Access Journals (Sweden)

    Rizzo Claudia


    Full Text Available Abstract The concept of Vascular Dementia (VaD has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case. Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment.

  12. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina


    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  13. Pathophysiology of vascular dementia


    Rizzo Claudia; Duro Giovanni; Iemolo Francesco; Castiglia Laura; Hachinski Vladimir; Caruso Calogero


    Abstract The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments th...

  14. Pulmonary vascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fedullo, P.F.; Shure, D.


    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

  15. Update on Vascular Dementia. (United States)

    Khan, Ayesha; Kalaria, Raj N; Corbett, Anne; Ballard, Clive


    Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment. © The Author(s) 2016.

  16. [How Treatable is Vascular Dementia?]. (United States)

    Mori, Etsuro


    Vascular dementia is an umbrella term, encompassing the pathological changes in the brain due to cerebrovascular disease that result in dementia. Vascular dementia is the second most common form of dementia, after Alzheimer's disease. In this paper, I outline the concept of vascular dementia, the key aspects of the disease that are yet to be clarified, and the current status of clinical trials. Assessing these factors, I discuss how treatable vascular dementia presently is. Use of the term'vascular dementia'is riddled with uncertainties regarding disease classification, and non-standardized diagnostic criteria. There are difficulties in determining the exact relationship between cerebrovascular pathology and cognitive impairment. The comorbid effects of Alzheimer's pathology in some individuals also present an obstacle to reliable clinical diagnosis, and hinder research into effective management approaches. Vascular dementia is preventable and treatable, as there are established primary and secondary prevention measures for the causative cerebrovascular diseases, such as vascular risk factor intervention, antiplatelet therapy, and anticoagulation, amongst others. However, unlike Alzheimer's disease, there are no established symptomatic treatments for vascular dementia. Clinical trials of cholinesterase inhibitors and memantine indicate that they produce small cognitive benefits in patients with vascular dementia, though the exact clinical significance of these is uncertain. Data are insufficient to support the widespread use of these drugs in vascular dementia. Rehabilitation and physical and cognitive exercise may be beneficial, but evidence of cognitive benefit and relief of neuropsychiatric symptoms due to exercise is lacking.

  17. [Estrogens and vascular thrombosis]. (United States)

    Colmou, A


    The incidence of thromboses among young women has increased with widespread use of oral contraceptives (OCs) due to the significant thromboembolic risk of estrogen. Estrogens intervene at the vascular, platelet, and plasma levels as a function of hormonal variations in the menstrual cycle, increasing the aggregability of the platelets and thrombocytes, accelerating the formation of clots, and decreasing the amount of antithrombin III. Estrogens are used in medicine to treat breast and prostate cancers and in gynecology to treat dysmenorrhea, during the menopause, and in contraception. Smoking, cardiovascular disease and hypertension, hypercholesterolemia, and diabetes are contraindicators to estrogen use. Thrombosis refers to blockage of a blood vessel by a clot or thrombus. Before estrogens are prescribed, a history of phlebitis, obesity, hyperlipidemia, or significant varicosities should be ruled out. A history of venous thrombosis, hyperlipoproteinemia, breast nodules, serious liver condition, allergies to progesterone, and some ocular diseases of vascular origin definitively rule out treatment with estrogens. A family history of infarct, embolism, diabetes, cancer, or vascular accidents at a young age signals a need for greater patient surveillance. All patients receiving estrogens should be carefully observed for signs of hypertension, hypercholesterolemia, hypercoagulability, or diabetes. Nurses have a role to play in carefully eliciting the patient's history of smoking, personal and family medical problems, and previous and current laboratory results, as well as in informing the patients of the risks and possible side effects of OCs, especially for those who smoke. Nurses should educate patients receiving estrogens, especially those with histories of circulatory problems, to avoid standing in 1 position for prolonged periods, avoid heat which is a vasodilator, avoid obesity, excercise regularly, wear appropriate footgear, and follow other good health

  18. Nanotechnology-based drug delivery systems

    Directory of Open Access Journals (Sweden)

    Singh Baljit


    Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

  19. Pulmonary delivery systems for polyphenols. (United States)

    Trotta, Valentina; Scalia, Santo


    This review reports on the beneficial pharmacological properties of naturally occurring polyphenols for the treatment of inflammatory pulmonary diseases. In addition, it presents an overview of the different types of inhalable formulations which have been developed in order to achieve efficient delivery of polyphenols to the respiratory tract. The main biological activities of polyphenols (anti-oxidant and anti-inflammatory) are covered, with particular emphasis on the studies describing their therapeutic effects on different factors and conditions characteristic of lung pathologies. Special focus is on the technological aspects which influence the pulmonary delivery of drugs. The various polyphenol-based inhalable formulations reported in the literature are examined with specific attention to the preparation methodologies, aerosol performance, lung deposition and in vitro and in vivo polyphenol uptake by the pulmonary epithelial cells.

  20. Anaesthesia for vascular emergencies. (United States)

    Ellard, L; Djaiani, G


    Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  1. Pediatric vascularized composite allotransplantation. (United States)

    Doumit, Gaby; Gharb, Bahar Bassiri; Rampazzo, Antonio; Papay, Francis; Siemionow, Maria Z; Zins, James E


    Vascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. Papers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. Although the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. Considering the non-life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.

  2. Extracranial vascular malformation: value of antenatal and postnatal MRI in management

    Energy Technology Data Exchange (ETDEWEB)

    Roche, C.J.; Pilling, D.W. [Dept. of Radiology, Royal Liverpool Children' s Hospital NHS Trust (United Kingdom); Walkinshaw, S.A. [Dept. of Fetal Medicine, Liverpool Women' s Hospital (United Kingdom); May, P.L. [Dept. of Neurosurgery, Royal Liverpool Children' s Hospital NHS Trust (United Kingdom)


    We report a case where fetal MRI using a low-field-strength magnet (0.5 T) accurately confirmed a large extracranial vascular malformation, which was suspected on antenatal US. Fetal MRI enabled better counselling of the parents and allowed suitable plans to be made regarding method of delivery and early management of the neonate. To our knowledge this is the first case of an extracranial vascular malformation imaged using fetal MRI. (orig.)

  3. Spinal Cord Vascular Disease

    Directory of Open Access Journals (Sweden)

    Abdoreza Ghoreishi


    Full Text Available The spinal cord is subject to many of the same vascular diseases that involve the brain, but its anatomy and embryology render it susceptible to some syndromes that do not have intracranial counterparts.The embryonic arterial supply to the spinal cord derives from intradural vessels that enter at each spinal level and divide to follow the dorsal and ventral roots. SPINAL CORD ISCHEMIA: The midthoracic levels of the spinal cord are traditionally considered to be the most vulnerable to compromise from hypoperfusion, but more recent evidence suggests that the lower thoracic cord is at greater risk . The actual prevalence of spinal cord infarction is unknown, but is generally cited as representing 1% to 2% of all central neurovascular events and 5% to 8% of all acute myelopathies. Weakness (100%, sensory loss (89%, back pain at onset (82%, and urinary complaints requiring catheterization (75% were the most common symptoms of cord ischemia at the time of presentation . Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction. Weakness most commonly affects both legs. Examination typically reveals flaccid paresis accompanied by diminished superficial and tendon reflexes below the level of the lesion. Preservation of strength and reflexes suggests the rare syndrome of posterior spinal artery territory infarction.   Aortic pathologies with regional hemodynamic compromise are the most common cause of spinal cord infarction, accounting for 30% to 40% of cases.                                                                                 The medical management of spinal cord ischemia is generally supportive and focused on reducing risk for

  4. Vaginal drug delivery systems: A Review of Current Status | Dobaria ...

    African Journals Online (AJOL)

    Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...

  5. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    Five patients with non-viable limbs had the vessel ligated. Conclusions. A TIVS in the damage control setting is both life- and limb-saving. These shunts can be inserted safely in a facility without access to a surgeon with vascular surgery experience if there is uncontrollable bleeding or the delay to definitive vascular surgery ...

  6. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    part of a damage control procedure, 7 patients were referred from a hospital without access to vascular surgical facilities with the TIVS in situ, and in the remaining 6 patients the TIVS was inserted during repair of a lower limb fracture with an associated vascular injury. Damage control procedure. Twenty-two patients had a ...

  7. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs. (United States)

    Elomaa, Laura; Yang, Yunzhi Peter


    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  8. Bypass materials in vascular surgery

    Directory of Open Access Journals (Sweden)

    Willich, Stephan N.


    Full Text Available Introduction: Arteriosclerotic changes can lead to circulatory disturbances in various areas of the human vascular system. In addition to pharmacological therapy and the management of risk factors (e. g. hypertension, diabetes, lipid metabolism disorders, and lifestyle, surgical interventions also play an important role in the treatment of arteriosclerosis. Long-segment arterial occlusions, in particular, can be treated successfully with bypass sur-gery. A number of different materials are available for this type of operation, such as autologous vein or pros-thetic grafts comprised of polytetrafluoroethylene (PTFE or Dacron®. Prosthetic materials are used especially in the treatment of peripheral artery disease, such as in aortoiliac or femoropopliteal bypass surgery. The present report will thus focus on this area in order to examine the effectiveness of different bypass materials. Among the efforts being made to refine the newly introduced DRG system in Germany, analysing the different bypass materials used in vascular surgery is particularly important. Indeed, in its current version the German DRG system does not distinguish between bypass materials in terms of reimbursement rates. Differences in cost structures are thus of especial interest to hospitals in their budget calculations, whereas both private and statutory health insurance funds are primarily interested in long-term results and their costs. Objectives: The goal of this HTA is to compare the different bypass materials used in vascular surgery in terms of their medical efficiency and cost-effectiveness, as well as with regard to their ethical, social and legal implications. In addition, this report aims to point out the areas in which further medical, epidemiological and health economic research is still needed. Methods: Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information

  9. Nano/Micro Formulations for Bacteriophage Delivery. (United States)

    Cortés, Pilar; Cano-Sarabia, Mary; Colom, Joan; Otero, Jennifer; Maspoch, Daniel; Llagostera, Montserrat


    Encapsulation methodologies allow the protection of bacteriophages for overcoming critical environmental conditions. Moreover, they improve the stability and the controlled delivery of bacteriophages which is of great innovative value in bacteriophage therapy. Here, two different encapsulation methodologies of bacteriophages are described using two biocompatible materials: a lipid cationic mixture and a combination of alginate with the antacid CaCO3. To perform bacteriophage encapsulation, a purified lysate highly concentrated (around 10(10)-10(11) pfu/mL) is necessary, and to dispose of a specific equipment. Both methodologies have been successfully applied for encapsulating Salmonella bacteriophages with different morphologies. Also, the material employed does not modify the antibacterial action of bacteriophages. Moreover, both technologies can also be adapted to any bacteriophage and possibly to any delivery route for bacteriophage therapy.

  10. Nutrition and vascular dementia. (United States)

    Perez, L; Heim, L; Sherzai, A; Jaceldo-Siegl, K; Sherzai, A


    The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies. Vascular dementia (VaD) is the second most common type of dementia. The prevalence of VaD continues to increase as the US population continues to grow and age. Currently, control of potential risk factors is believed to be the most effective means of preventing VaD. Thus, identification of modifiable risk factors for VaD is crucial for development of effective treatment modalities. Nutrition is one of the main modifiable variables that may influence the development of VaD. A systematic review of literature was conducted using the PubMed, Web of Science, and CINAHL Plus databases with search parameters inclusive of vascular dementia, nutrition, and vascular cognitive impairment (VCI). Fourteen articles were found that proposed a potential role of specific nutritional components in VaD. These components included antioxidants, lipids, homocysteine, folate, vitamin B12, and fish consumption. Antioxidants, specifically Vitamin E and C, and fatty fish intake were found to be protective against VaD risk. Fried fish, elevated homocysteine, and lower levels of folate and vitamin B12 were associated with increased VaD. Evidence for dietary lipids was inconsistent, although elevated midlife serum cholesterol may increase risk, while late-life elevated serum cholesterol may be associated with decreased risk of VaD. Currently, the most convincing evidence as to the relationship between VaD and nutrition exists for micronutrients, particularly Vitamin E and C. Exploration of nutrition at the macronutrient level and additional long term prospective cohort studies are warranted to better understand the role of nutrition in VaD disease development and progression. At present, challenges in this research include limitations in sample size, which was commonly cited. Also, a variety of diagnostic criteria for VaD were employed in the studies

  11. The Danish Vascular Registry, Karbase

    Directory of Open Access Journals (Sweden)

    Eldrup N


    Full Text Available Nikolaj Eldrup,1,2 Charlotte Cerqueira,3 Louise de la Motte,2,4 Lisbet Knudsen Rathenborg,2,4 Allan K Hansen2,5 1Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, 2Karbase, The Danish Vascular Registry, Aarhus, 3Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Capital Region of Denmark, 4Department of Vascular Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 5Department of Vascular Surgery, Aalborg University Hospital, Aalborg, Denmark Aim: The Danish Vascular Registry (DVR, Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry for quality assessment and research. Study population: All patients undergoing vascular interventions (surgical and endovascular at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ~9,000 procedures are added. By January 2016, .180,000 procedures have been recorded. Since 2001, data completeness has been .90% (compared to the Danish National Patient Register. Main variables: Variables include information on descriptive patient data (ie, age, sex, height, and weight and comorbidity (ie, previous cardiovascular disease and diabetes. Process variable includes waiting time (time from event to medical contact and treatment and the type of procedures conducted. Outcome variables for in-hospital complications (ie, wound complications, myocardial infarction, stroke, amputation, respiratory complications, and renal insufficiency and 30-day patency are submitted. Variables for medical treatment (antithrombotic and statin treatment, amputation, and survival are extracted from nationwide, administrative registers. Conclusion: The DVR reports outcome on key indicators for

  12. Diagnostic criteria for vascular dementia

    NARCIS (Netherlands)

    Scheltens, P.; Hijdra, A. H.


    The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria

  13. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings


    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  14. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri


    Full Text Available Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial.

  15. The Danish Vascular Registry, Karbase

    DEFF Research Database (Denmark)

    Eldrup, Nikolaj; Cerqueira, Charlotte; de la Motte, Louise


    AIM: The Danish Vascular Registry (DVR), Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry...... for quality assessment and research. STUDY POPULATION: All patients undergoing vascular interventions (surgical and endovascular) at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ∼9,000 procedures are added. By January 2016, >180,000 procedures...... have been recorded. Since 2001, data completeness has been >90% (compared to the Danish National Patient Register). MAIN VARIABLES: Variables include information on descriptive patient data (ie, age, sex, height, and weight) and comorbidity (ie, previous cardiovascular disease and diabetes). Process...

  16. Social media in vascular surgery. (United States)

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E


    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  17. Language Policy and Methodology (United States)

    Liddicoat, Antony J.


    The implementation of a language policy is crucially associated with questions of methodology. This paper explores approaches to language policy, approaches to methodology and the impact that these have on language teaching practice. Language policies can influence decisions about teaching methodologies either directly, by making explicit…

  18. Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma


    Byrne, James D.; Jajja, Mohammad R. N.; Schorzman, Allison N.; Keeler, Amanda W.; Luft, J. Christopher; Zamboni, William C.; DeSimone, Joseph M.; Yeh, Jen Jen


    Drug delivery to pancreatic tumors is impaired by a unique desmoplastic response and poor tumor vascularization. A drug delivery device capable of overcoming these barriers could provide substantial benefit for patients with pancreatic cancer. In this study, we show that local iontophoretic delivery of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in better tumor response and tolerability compared with i.v. FOLFIRINOX. Given the low systemic exposu...

  19. Noninfarct vascular dementia and Alzheimer dementia spectrum. (United States)

    Emery, V Olga; Gillie, Edward X; Smith, Joseph A


    Vascular dementia is an overarching superordinate category of which multiinfarct vascular dementia is only one subtype. To contribute to the definition of vascular dementia, method involved investigation of mental status, oral language and comprehension in 81 consecutive vascular patients comprising two vascular samples: cerebral infarct sample (n=43) and cerebral noninfarct sample (n=38). To determine baseline, method also involved investigation of 36 demographically equivalent normal elderly. Results indicate both vascular samples performed significantly worse than normal elderly. Results further indicate there were no robust, reliable, significant differences between cerebral infarct and cerebral noninfarct patients. The lack of significant differences between cerebral infarct and cerebral noninfarct vascular samples brings into focus the ambiguous transition between diffuse, generalized disease and the multifocality underlying the vascular dementia-Alzheimer dementia spectrum. Cross-cutting infarct and noninfarct vascular populations were vascular factors of arteriosclerosis, abnormal blood pressure, diabetes mellitus, abnormal electrocardiogram, peripheral vascular disease, and other variables implicated in the distal causality of both infarct and noninfarct vascular dementias. Results indicate cerebral infarction is not the only path to the final common phenotype of vascular dementia. Vascular dementia is reconceptualized so as to include noninfarct vascular dementia: vascular dementia caused by underlying vascular factors other than cerebral infarction. It is suggested that one form of the subtype of noninfarct vascular dementia is Alzheimer-type vascular dementia.

  20. Comparative Study on Agile software development methodologies


    Moniruzzaman, A. B. M.; Hossain, Dr Syed Akhter


    Today-s business environment is very much dynamic, and organisations are constantly changing their software requirements to adjust with new environment. They also demand for fast delivery of software products as well as for accepting changing requirements. In this aspect, traditional plan-driven developments fail to meet up these requirements. Though traditional software development methodologies, such as life cycle-based structured and object oriented approaches, continue to dominate the sys...

  1. Thermosensitive hydrogels a versatile concept adapted to vaginal drug delivery. (United States)

    Taurin, Sebastien; Almomen, Aliyah A; Pollak, Tatianna; Kim, Sun Jin; Maxwell, John; Peterson, C Matthew; Owen, Shawn C; Janát-Amsbury, Margit M


    Vaginal drug delivery represents an attractive strategy for local and systemic delivery of drugs otherwise poorly absorbed after oral administration. The rather dense vascular network, mucus permeability and the physiological phenomenon of the uterine first-pass effect can all be exploited for therapeutic benefit. However, several physiological factors such as an acidic pH, constant secretion, and turnover of mucus as well as varying thickness of the vaginal epithelium can impact sustained drug delivery. In recent years, polymers have been designed to tackle challenges mentioned above. In particular, thermosensitive hydrogels hold great promise due to their stability, biocompatibility, adhesion properties and adjustable drug release kinetics. Here, we discuss the physiological and anatomical uniqueness of the vaginal environment and how it impacts the safe and efficient vaginal delivery and also reviewed several thermosensitive hydrogels deemed suitable for vaginal drug delivery by addressing specific characteristics, which are essential to engage the vaginal environment successfully.

  2. Assisted Vaginal Delivery (United States)

    ... prescription. If sitting is uncomfortable, sit on a pillow. There also are special cushions that may be ... vagina. Cesarean Delivery: Delivery of a baby through surgical incisions made in the mother’s abdomen and uterus. ...

  3. Depression in vascular dementia. (United States)

    Naarding, Paul; de Koning, Inge; dan Kooten, Fop; Dippel, Diederik W J; Janzing, Joost G E; van der Mast, Rose C; Koudstaal, Peter J


    To study the presence of different dimensions of depression in subjects with vascular dementia. After a stroke, cognitive, affective and behavioural disturbances are common. It has been suggested that the nature of affective symptomatology can help to differentiate organic from psychological depression. Cognitive and affective symptoms were assessed in 78 stroke patients and a principal component analysis was performed on these symptoms. Also, a discriminant analysis was carried out to establish the contribution of different symptoms on the diagnosis 'depressive disorder' and 'dementia'. (1) Principal component analysis revealed three distinct sub-syndromes: one with predominantly mood symptoms, one with essentially psychomotor symptoms, and one with vegetative symptoms; (2) mood, psychomotor and vegetative symptoms were all independently and strongly related to a diagnosis of major depressive disorder according to DSM-III-R criteria; (3) the psychomotor factor was also firmly associated with dementia; and (4) discriminant analysis gave further support for our conclusion that some of the depressive features, in particular the psychomotor factor, are at least partly related to the organic brain damage from stroke. The results indicate that different dimensions of depression could be discerned in a group of stroke patients and that the symptom profile of depression in these patients can be affected by the presence of dementia. Copyright 2003 John Wiley & Sons, Ltd.

  4. [Extremity vascular traumas]. (United States)

    Angelini, Romeo; Rutolo, Ferdinando; Cozzolino, Giuseppe; D'Amario, Vanessa; Spigonardo, Francesca


    The Authors report on a series of 61 vascular traumas treated over a 7 years, separated in two groups. The first one includes 35 cases, that are street accidents, on the work and gunshot wounds. The second group includes 26 iatrogenic causes due to arterial catheterism. All patients underwent ecocolor Doppler directly in the operating theatre and, when this diagnostic procedure was not enough, pre-operating angiography was used (10 cases of complex traumas of the lower limb). One death was reported far each groups (3.27%). In 55 cases (90.1%), limb savage was achieved. In the others 4 (6.93%) of the first group, limb demolition was necessary for different causes. In the first group, severe neurological sequelaes were observed in 2 cases and motor deficits caused by tendon lesions in 1 case. The good results obtained are the result of the short ischemic interval between the acute event and treatment, thanks to a multidisciplinary approach of a specific equipe, that is rapid as possible.

  5. Vascular injuries during gynecological laparoscopy: the vascular surgeon's advice

    Directory of Open Access Journals (Sweden)

    Marcello Barbosa Barros

    Full Text Available CONTEXT: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services. CASES: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period. DISCUSSION: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

  6. Trauma vascular, visión del cirujano vascular

    Directory of Open Access Journals (Sweden)

    Dr. D. Cristián Salas


    Full Text Available El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesiones de vasos torácicos y abdominales requieren de imágenes de apoyo, siempre que el paciente se encuentre estabilizado, generalmente tomografía axial computada. La mayoría de las lesiones vasculares son por trauma penetrante, comprometiendo principalmente las extremidades. Con el desarrollo de los procedimientos invasivos vasculares en los últimos años se ha observado un aumento de lesiones vasculares iatrogénicas. Hoy en día muchos pacientes con trauma vascular son manejados por vía endovascular.

  7. Role of preoperative vascular ultrasonography in hemodialysis vascular access operation. (United States)

    Siribumrungwong, Boonying; Tomtitchong, Prakitpunthu; Kanpirom, Kitti


    Preoperative vascular mapping increase rate of successful hemodialysis vascular access operation. Several studies recommend using this procedure routinely. But some studies recommend using this procedure in selected patients. So this study aims to determine the impacts of preoperative vascular mapping in unfavorable-examined patients. 55 patients were studied retrospectively from August 2006 to October 2009. Before April 2008, the operative plans were based on physical examination (group 1). After April 2008, the surgeon did preoperative vascular mapping prior to the operation in unfavorable-examined patients (group 2). The results were compared. There were high maturation rates in favorable-examined patients. In unfavorable-examined patients, preoperative vascular mapping can identified nonpalpable favorable vein which successful maturation of 18.75%. Complementary duplex scan decrease rate of unsuccessful operation significantly (p = 0.037) but does not increase maturation rate. Careful physical examination is important part before operation. Preoperative vascular mapping has benefit only in patients with unfavorable-examined patients. It finds some nonpalpable favorable vein and decrease unsuccessful exploration.

  8. UAV Delivery Monitoring System

    Directory of Open Access Journals (Sweden)

    San Khin Thida


    Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.

  9. Diabetes and Retinal Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin


    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  10. ( Elaeis guineensis Jacq ) vascular wilt

    African Journals Online (AJOL)

    Effet de la jachére sur l'expérimentation de la fusariose vasculaire du palmier à huile ( Elaeis guineensis Jacq ) : Effects of the fallow in the expression of oil-palm ( Elaeis guineensis Jacq ) vascular wilt.

  11. Scenario development methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Eng, T. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Hudson, J. [Rock Engineering Consultants, Welwyn Garden City, Herts (United Kingdom); Stephansson, O. [Royal Inst. of Tech., Stockholm (Sweden). Div. of Engineering Geology; Skagius, K.; Wiborgh, M. [Kemakta, Stockholm (Sweden)


    In the period 1981-1994, SKB has studied several methodologies to systematize and visualize all the features, events and processes (FEPs) that can influence a repository for radioactive waste in the future. All the work performed is based on the terminology and basic findings in the joint SKI/SKB work on scenario development presented in the SKB Technical Report 89-35. The methodologies studied are (a) Event tree analysis, (b) Influence diagrams and (c) Rock Engineering Systems (RES) matrices. Each one of the methodologies is explained in this report as well as examples of applications. One chapter is devoted to a comparison between the two most promising methodologies, namely: Influence diagrams and the RES methodology. In conclusion a combination of parts of the Influence diagram and the RES methodology is likely to be a promising approach. 26 refs.

  12. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line


    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... vasculature may affect the retinal response to potential vascular disease in later life....

  13. Language policy and methodology


    Liddicoat, Antony J.


    The implementation of a language policy is crucially associated with questions of methodology. This paper explores approaches to language policy, approaches to methodology and the impact that these have on language teaching practice. Language policies can influence decisions about teaching methodologies either directly, by making explicit recommendations about the methods to be used in classroom practice, or indirectly, through the conceptualisation of language leaming which underlies the pol...

  14. The Danish Vascular Registry, Karbase (United States)

    Eldrup, Nikolaj; Cerqueira, Charlotte; de la Motte, Louise; Rathenborg, Lisbet Knudsen; Hansen, Allan K


    Aim The Danish Vascular Registry (DVR), Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry for quality assessment and research. Study population All patients undergoing vascular interventions (surgical and endovascular) at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ∼9,000 procedures are added. By January 2016, >180,000 procedures have been recorded. Since 2001, data completeness has been >90% (compared to the Danish National Patient Register). Main variables Variables include information on descriptive patient data (ie, age, sex, height, and weight) and comorbidity (ie, previous cardiovascular disease and diabetes). Process variable includes waiting time (time from event to medical contact and treatment) and the type of procedures conducted. Outcome variables for in-hospital complications (ie, wound complications, myocardial infarction, stroke, amputation, respiratory complications, and renal insufficiency) and 30-day patency are submitted. Variables for medical treatment (antithrombotic and statin treatment), amputation, and survival are extracted from nationwide, administrative registers. Conclusion The DVR reports outcome on key indicators for monitoring the quality at all vascular departments in Denmark for the purpose of quality improvement. Furthermore, data are available for research and are being used in international collaborations on changes in clinical practices. PMID:27822118

  15. [Cutaneous vascular anomalies in children]. (United States)

    Yilmaz, L; Kacenelenbogen, N


    Vascular anomalies, which are erroneously categorized under the term angiomas, are a highly heterogeneous group of lesions that are poorly understood and affect a mean of 5 to 10 % of children. The fortuitous discovery of propranolol's efficacy in one of these entities has made them a topical issue. The paper's main objective is to inform family doctors of the various types of vascular anomalies, clarify their classification, and provide a common terminology. Its secondary objective is to provide a decision tree that enables primary care doctors to avoid diagnostic pitfalls, successfully detect cases, and optimize management. Systematic review. According to a recent study, 71,3 % of publications use the term hemangioma erroneously, regardless of the authors' field. The key for family doctors is to use one international classification only, that of the International Society for the Study of Vascular Anomalies (ISSVA), in order to facilitate management and comprehension between the different healthcare levels. The diagnosis of vascular anomalies is clinical in 90 % of cases, so all family doctors can, whilst using a decision tree, diagnose a vascular anomaly and refer only those that are complex for specialist care. The most common vascular anomaly is infantile hemangioma in infants, which spontaneously regresses around the age of 5-7 years in 90 % of cases. Watchful waiting and regular follow-up suffice, therefore, in such settings.

  16. Suitability of Exoseal Vascular Closure Device for Antegrade Femoral Artery Puncture Site Closure

    Energy Technology Data Exchange (ETDEWEB)

    Schmelter, Christopher, E-mail:; Liebl, Andrea; Poullos, Nektarios [Klinikum Ingolstadt, Department of Diagnostic and Interventional Radiology (Germany); Ruppert, Volker [Klinikum Ingolstadt, Department of Vascular Surgery (Germany); Vorwerk, Dierk [Klinikum Ingolstadt, Department of Diagnostic and Interventional Radiology (Germany)


    Purpose. To assess the efficacy and safety of the Exoseal vascular closure device for antegrade puncture of the femoral artery. Methods. In a prospective study from February 2011 to January 2012, a total of 93 consecutive patients received a total of 100 interventional procedures via an antegrade puncture of the femoral artery. An Exoseal vascular closure device (6F) was used for closure in all cases. Puncture technique, duration of manual compression, and use of compression bandages were documented. All patients were monitored by vascular ultrasound and color-coded duplex sonography of their respective femoral artery puncture site within 12 to 36 h after angiography to check for vascular complications. Results. In 100 antegrade interventional procedures, the Exoseal vascular closure device was applied successfully for closure of the femoral artery puncture site in 96 cases (96 of 100, 96.0 %). The vascular closure device could not be deployed in one case as a result of kinking of the vascular sheath introducer and in three cases because the bioabsorbable plug was not properly delivered to the extravascular space adjacent to the arterial puncture site, but instead fully removed with the delivery system (4.0 %). Twelve to 36 h after the procedure, vascular ultrasound revealed no complications at the femoral artery puncture site in 93 cases (93.0 %). Minor vascular complications were found in seven cases (7.0 %), with four cases (4.0 %) of pseudoaneurysm and three cases (3.0 %) of significant late bleeding, none of which required surgery. Conclusion. The Exoseal vascular closure device was safely used for antegrade puncture of the femoral artery, with a high rate of procedural success (96.0 %), a low rate of minor vascular complications (7.0 %), and no major adverse events.

  17. Screening of siRNA Nanoparticles for Delivery to Airway Epithelial Cells Using High Content Analysis


    Hibbitts, Alan; Lieggi, Nora; McCabe, Olive; Thomas, Warren; Barlow, James; O'Brien, Fiona; Cryan, Sally-Ann


    Background: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop novel methods of treating a range of poorly treated respiratory conditions. However progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery Methodology: Following physico-chemical analysis, the ability of PEI-PEG/siRNA nanoparticles to facilitate siRNA delivery was det...

  18. Non-invasive optical modulation of local vascular permeability (United States)

    Choi, Myunghwan; Choi, Chulhee


    For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

  19. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding (United States)

    Reinert, Rachel B.; Cai, Qing; Hong, Ji-Young; Plank, Jennifer L.; Aamodt, Kristie; Prasad, Nripesh; Aramandla, Radhika; Dai, Chunhua; Levy, Shawn E.; Pozzi, Ambra; Labosky, Patricia A.; Wright, Christopher V. E.; Brissova, Marcela; Powers, Alvin C.


    Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers. PMID:24574008

  20. Narrative Visual Methodologies

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth


    The paper has a methodological focus, discussed in relation to examples from an auto-ethnographic study with the working title Family Anecdotes. The main methodological question is how to map storytelling practice as a process for unfolding multiple cultural and social contexts of meaning using a...

  1. Introduction to LCA Methodology

    DEFF Research Database (Denmark)


    In order to offer the reader an overview of the LCA methodology in the preparation of the more detailed description of its different phases, a brief introduction is given to the methodological framework according to the ISO 14040 standard and the main elements of each of its phases. Emphasis is o...

  2. Data Centric Development Methodology (United States)

    Khoury, Fadi E.


    Data centric applications, an important effort of software development in large organizations, have been mostly adopting a software methodology, such as a waterfall or Rational Unified Process, as the framework for its development. These methodologies could work on structural, procedural, or object oriented based applications, but fails to capture…

  3. The Methodology of Magpies (United States)

    Carter, Susan


    Arts/Humanities researchers frequently do not explain methodology overtly; instead, they "perform" it through their use of language, textual and historic cross-reference, and theory. Here, methodologies from literary studies are shown to add to Higher Education (HE) an exegetical and critically pluralist approach. This includes…

  4. Archetype Modeling Methodology. (United States)

    Moner, David; Alberto Maldonado, José; Robles, Montserrat


    Clinical Information Models (CIMs) expressed as archetypes play an essential role in the design and development of current Electronic Health Record (EHR) information structures. Although there exist many experiences about using archetypes in the literature, a comprehensive and formal methodology for archetype modeling does not exist. Having a modeling methodology is essential to develop quality archetypes, in order to guide the development of EHR systems and to allow the semantic interoperability of health data. In this work, an archetype modeling methodology is proposed. This paper describes its phases, the inputs and outputs of each phase, and the involved participants and tools. It also includes the description of the possible strategies to organize the modeling process. The proposed methodology is inspired by existing best practices of CIMs, software and ontology development. The methodology has been applied and evaluated in regional and national EHR projects. The application of the methodology provided useful feedback and improvements, and confirmed its advantages. The conclusion of this work is that having a formal methodology for archetype development facilitates the definition and adoption of interoperable archetypes, improves their quality, and facilitates their reuse among different information systems and EHR projects. Moreover, the proposed methodology can be also a reference for CIMs development using any other formalism. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Bioadhesive delivery systems for mucosal vaccine delivery. (United States)

    Baudner, Barbara C; O'Hagan, Derek T


    Mucosal vaccine delivery potentially induces mucosal as well as systemic immune responses and may have advantages particularly for optimal protection against pathogens that infect the host through mucosal surfaces. However, the delivery of antigens through mucosal membranes remains a major challenge due to unfavorable physiological conditions (pH and enzymes) and significant biological barriers, which restrict the uptake of antigens. To improve mucosal vaccine delivery, the use of bioadhesive delivery systems offers numerous advantages, including protection from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time, and/or targeting them to sites of antigen uptake. Although some bioadhesives have direct immune stimulating properties, it appears most likely that successful mucosal vaccination will require the addition of vaccine adjuvants for optimal immune responses, particularly if they are to be used in an unprimed population. Thus, complex vaccine formulations and delivery strategies have to be carefully designed to appropriately stimulate immune response for the target pathogen. In addition, careful consideration is needed to define the "best" route for mucosal immunization for each individual pathogen.

  6. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck


    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... and hydrophobic domains, the overall hydrophilic mucus also presents an interactive barrier limiting the free diffusion of components within and through the mucus. Furthermore, mucus is a dynamic barrier due to its continuous secretion and shedding from the mucosal surfaces. Mucus is thus a highly complex gel...... barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well...

  7. Project delivery system (PDS)

    CERN Document Server


    As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

  8. In vitro assessment of mouse fetal abdominal aortic vascular function. (United States)

    Renshall, Lewis J; Dilworth, Mark R; Greenwood, Susan L; Sibley, Colin P; Wareing, Mark


    Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II (Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function. Copyright © 2014 the American Physiological Society.

  9. Imaging of peripheral vascular disease

    Directory of Open Access Journals (Sweden)

    Mo Al-Qaisi


    Full Text Available Mo Al-Qaisi1, David M Nott1, David H King1, Sam Kaddoura2, Mo Hamady31Charing Cross Hospital, London, UK; 2Royal Brompton Hospital, London, UK; 3St. Mary’s Hospital, London, UKAbstract: This illustrated review article gives an evidence-based update on the different modalities used for imaging peripheral vascular disease (duplex ultrasound, computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography. After discussing the latest technological developments for each modality, their limitations are also highlighted. The evidence is presented for the various modalities’ roles in the imaging of peripheral vascular disease, including problem-solving applications. The strengths and weaknesses of each modality are therefore critically appraised, including the salient technological, clinical, and financial aspects. This review allows the general and specialist practitioner to make an informed decision on how best to deploy imaging tests in peripheral vascular disease as part of an evidence-based approach. The article concludes with a rational imaging algorithm for the investigation of peripheral vascular disease.Keywords: imaging, peripheral, vascular, duplex, angiography, arterial 

  10. Optimal treatment of vascular birthmarks. (United States)

    Werner, Jochen A; Dünne, Anja A; Lippert, Burkard M; Folz, Benedikt J


    Optimal functional and cosmetic outcomes for vascular lesions require a thorough preoperative diagnosis of vascular anomalies, since correct classification of each vascular lesion has a direct influence on the treatment of choice. Many different classification systems have been discussed controversially. Based on clinical practicality and significant accuracy of forecast with regard to the clinical course of a lesion, Mulliken and Glowacki's biologic classification gained most clinical relevance and has become accepted as the official classification scheme by the International Society for the Study of Vascular Anomalies (ISSVA). Based on comprehensive description of relevant literature results, the current communication shall give an overview of differing, internationally accepted treatments. Although conservative management can be proposed for uncomplicated hemangiomas occurring in infancy, the proliferative progression of these lesions provides an adequate indication for treatment, while vascular malformations, which usually persist throughout life, always require therapeutic intervention if they start to cause clinical symptoms. Based on individual parameters (such as diameter, location and growth dynamics), different treatments, including cryotherapy, corticosteroids, laser therapy, sclerotherapy, surgery, and/or embolization, can be performed successfully. Currently, however, none of these treatments represents the solitary treatment of choice.

  11. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)


    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  12. Trauma vascular, visión del cirujano vascular


    Dr. D. Cristián Salas


    El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesi...

  13. WLAN Technologies for Audio Delivery

    Directory of Open Access Journals (Sweden)

    Nicolas-Alexander Tatlas


    Full Text Available Audio delivery and reproduction for home or professional applications may greatly benefit from the adoption of digital wireless local area network (WLAN technologies. The most challenging aspect of such integration relates the synchronized and robust real-time streaming of multiple audio channels to multipoint receivers, for example, wireless active speakers. Here, it is shown that current WLAN solutions are susceptible to transmission errors. A detailed study of the IEEE802.11e protocol (currently under ratification is also presented and all relevant distortions are assessed via an analytical and experimental methodology. A novel synchronization scheme is also introduced, allowing optimized playback for multiple receivers. The perceptual audio performance is assessed for both stereo and 5-channel applications based on either PCM or compressed audio signals.

  14. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line


    , the branching pattern of the retinal vessels demonstrated a higher structural similarity in monozygotic than in dizygotic twin pairs. The retinal vascular fractal dimension was mainly determined by genetic factors, which accounted for 54% of the variation. The genetically predetermination of the retinal......Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs......, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation. Results: The mean...

  15. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale


    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  16. [Alzheimer's disease and vascular dementia]. (United States)

    Nagata, Ken


    Alzheimer's disease (AD) and vascular dementia (VaD) are the two major forms of dementia in the elderly, and they had been separated categorically on the basis of pathogenetic mechanisms and clinical operationalized criteria. However, it was claimed that this strict separation might steered toward the overdiagnosis of vascular dementia, this dichotomy has been reevaluated in the light of recent epidemiological and neuropathological knowledge. Cerebrovascular disease (CVD) is now considered as one of the vascular risk factors to the onset and evolution of Alzheimer's disease. Futhermore, the term "AD with CVD" has been used to classify patients fulfilling the clinical criteria for possible AD and who also present clinical or brain imaging evidence of relevant CVD.

  17. Vascular education and training in Asia. (United States)

    Jirasiritham, Sopon


    Cardiovascular diseases have become more prevalent and threatening to the health of the population of Asia due to the rapidly growing number of aging people. The Asian Society for Vascular Surgery unites 13 member organizations: Japan, Korea, China, India, Hong Kong, Singapore, Malaysia, Taiwan, Bangladesh, Philippines, Saudi Arabia, Indonesia, and Thailand. The essential mission of the Asian Society for Vascular Surgery is to improve training in vascular surgery to increase the number of competent vascular surgeons in Asia. Almost every member country has its own vascular training program. Most curricula for vascular surgery training are composed of basic vascular research, clinical vascular medicine, vascular investigation, and open and endovascular surgery, with the period of training ranging from 2 to 4 years.

  18. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro


    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  19. Prediction of preterm delivery

    NARCIS (Netherlands)

    Wilms, F.F.


    Preterm delivery is in quantity and in severity an important issue in the obstetric care in the Western world. There is considerable knowledge on maternal and obstetric risk factors of preterm delivery. Of the women presenting with preterm labor, the majority is pregnant with a male fetus and in

  20. [The moon and delivery]. (United States)

    Romero Martínez, Jorge; Guerrero Guijo, Inmaculada; Artura Serrano, Antonio


    In different cultures and mythologies, the moon is related with fertility, pregnancy and delivery. Professional obstetricians also notice an increase in care demands on the days when the moon is full. Many studies have been made which try to correlate delivery processes to the phases of the moon with contradictory results. The authors plan to try to find any basis in fact which support these popular beliefs and to discover if lunar phases bear an influence on the distribution of deliveries. They carried out a descriptive transversal study on a total of 1715 unassisted deliveries over the course of ten complete lunar cycles. The authors have carried out a descriptive and inferential analysis, a one way ANOVA and a Kruskal Wallis test on their three data bases which are general, primipara and multipara in which they contemplated the total number of deliveries per phase, the mean of each phase, as well as the central day in each phase of the lunar cycle. The differences found in the distribution of deliveries over the four lunar phases, along with the comparison of the means and the comparison of the number of deliveries on the central day in each phase are not statistically significant. The different phases in the lunar cycle and especially the full moon do not appear to have any influence over the distribution of deliveries in this study.

  1. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Larsen, Marcus M.; Bharati, Pratyush


    This article examines antecedents and performance implications of global delivery models (GDMs) in global business services. GDMs require geographically distributed operations to exploit both proximity to clients and time-zone spread for efficient service delivery. We propose and empirically show...

  2. Clinical trial methodology

    National Research Council Canada - National Science Library

    Peace, Karl E; Chen, Ding-Geng


    "Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide...

  3. VEM: Virtual Enterprise Methodology

    DEFF Research Database (Denmark)

    Tølle, Martin; Vesterager, Johan


    This chapter presents a virtual enterprise methodology (VEM) that outlines activities to consider when setting up and managing virtual enterprises (VEs). As a methodology the VEM helps companies to ask the right questions when preparing for and setting up an enterprise network, which works as a b...... as a breeding ground for setting up VEs. The VEM applies the Virtual Enterprise Reference Architecture (VERA) as an underlying structure. Both VEM and VERA are developed as a part of the GLOBEMEN project.......This chapter presents a virtual enterprise methodology (VEM) that outlines activities to consider when setting up and managing virtual enterprises (VEs). As a methodology the VEM helps companies to ask the right questions when preparing for and setting up an enterprise network, which works...

  4. Design Methodology - Design Synthesis

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup


    Design Methodology is part of our practice and our knowledge about designing, and it has been strongly supported by the establishing and work of a design research community. The aim of this article is to broaden the reader¿s view of designing and Design Methodology. This is done by sketching...... the development of Design Methodology through time and sketching some important approaches and methods. The development is mainly forced by changing industrial condition, by the growth of IT support for designing, but also by the growth of insight into designing created by design researchers.......ABSTRACT Design Methodology shall be seen as our understanding of how to design; it is an early (emerging late 60ies) and original articulation of teachable and learnable methodics. The insight is based upon two sources: the nature of the designed artefacts and the nature of human designing. Today...

  5. Transparent Guideline Methodology Needed

    DEFF Research Database (Denmark)

    Lidal, Ingeborg; Norén, Camilla; Mäkelä, Marjukka


    Group.2 Similar criteria for guideline quality have been suggested elsewhere.3 Our conclusion was that this much needed guideline is currently unclear about several aspects of the methodology used in developing the recommendations. This means potential users cannot be certain that the recommendations...... are based on best currently available evidence. Our concerns are in two main categories: the rigor of development, including methodology of searching, evaluating, and combining the evidence; and editorial independence, including funding and possible conflicts of interest....

  6. Introduction to LCA Methodology

    DEFF Research Database (Denmark)


    In order to offer the reader an overview of the LCA methodology in the preparation of the more detailed description of its different phases, a brief introduction is given to the methodological framework according to the ISO 14040 standard and the main elements of each of its phases. Emphasis is o...... where additional work contributes most to strengthen the results and conclusions of the study....

  7. Microneedles for intradermal and transdermal delivery (United States)

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F


    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  8. Telephone based self-management support by 'lay health workers' and 'peer support workers' to prevent and manage vascular diseases: a systematic review and meta-analysis. (United States)

    Small, Nicola; Blickem, Christian; Blakeman, Tom; Panagioti, Maria; Chew-Graham, Carolyn A; Bower, Peter


    Improved prevention and management of vascular disease is a global priority. Non-health care professionals (such as, 'lay health workers' and 'peer support workers') are increasingly being used to offer telephone support alongside that offered by conventional services, to reach disadvantaged populations and to provide more efficient delivery of care. However, questions remain over the impact of such interventions, particularly on a wider range of vascular related conditions (such as, chronic kidney disease), and it is unclear how different types of telephone support impact on outcome. This study assessed the evidence on the effectiveness and cost-effectiveness of telephone self-management interventions led by 'lay health workers' and 'peer support workers' for patients with vascular disease and long-term conditions associated with vascular disease. Systematic review of randomised controlled trials. Three electronic databases were searched. Two authors independently extracted data according to the Cochrane risk of bias tool. Random effects meta-analysis was used to pool outcome measures. Ten studies were included, primarily based in community settings in the United States; with participants who had diabetes; and used 'peer support workers' that shared characteristics with patients. The included studies were generally rated at risk of bias, as many methodological criteria were rated as 'unclear' because of a lack of information.Overall, peer telephone support was associated with small but significant improvements in self-management behaviour (SMD = 0.19, 95% CI 0.05 to 0.33, I2 = 20.4%) and significant reductions in HbA1c level (SMD = -0.26, 95% CI -0.41 to -0.11, I2 = 47.6%). There was no significant effect on mental health quality of life (SMD = 0.03, 95% CI -0.12 to 0.18, I2 = 0%). Data on health care utilisation were very limited and no studies reported cost effectiveness analyses. Positive effects were found for telephone self-management interventions via 'lay

  9. Vascular ultrasound for atherosclerosis imaging

    NARCIS (Netherlands)

    C.L. de Korte (Chris); H.H.G. Hansen (Hendrik); A.F.W. van der Steen (Ton)


    textabstractCardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the

  10. Signaling circuitry in vascular morphogenesis. (United States)

    Warren, Carmen M; Iruela-Arispe, M Luisa


    In this mini-review, we have highlighted the recent breakthroughs in growth factor signaling that have made conceptual changes in our understanding of how blood vessels are formed. Studies conducted over the past few years have focused on understanding the cell biology of vascular morphogenesis. The major themes include characterization of the different cell types that comprise a vascular sprout, as well as the regulatory influence of cell-cell and cell-matrix interactions on signaling outcomes. In addition, novel trends have emerged, including nonconventional ways in which vascular endothelial growth factor contributes to cell survival and metabolic balance. The growth of new capillary sprouts from a preexisting vascular network requires a highly coordinated cellular response to both growth factors and morphogens. This response is sensed and triggered by cell surface receptors responsible for the activation of an intracellular cascade that efficiently initiates migration and proliferation programs. While the molecular players that coordinate these effects have been identified, recent findings have expanded our understanding of how context, in particular cell-cell and cell-matrix interactions, affects endothelial cell responses to growth factors.

  11. Vascular complications in orthopedic surgery. (United States)

    Chervu, A; Quinones-Baldrich, W J


    Vascular complications may be seen secondary to trauma or in the perioperative period following elective surgery. Prompt recognition and correction of these problems are of utmost importance to assure functional viability of the affected extremity. Evaluation may be complicated by the presence of preexisting atherosclerotic occlusive disease in the elderly patient. Relevant points in the history and physical examination include mechanism of injury, preexisting disease, evaluation of motor and sensory function, and presence and character of pulses. Noninvasive vascular studies should be obtained in all patients. Absolute indications for angiography include absent pulses, signs and symptoms of ischemia, a bruit, and a posterior knee dislocation; decreased pulses, a significant hematoma, and proximity of the fracture fragment are relative indications. Controversial issues in the management of combined orthopedic and vascular injuries include the use of internal versus external fixation, the use of prosthetic versus autogenous material, and the need for venous reconstruction. Popliteal artery trauma is still associated with a high limb loss rate, and careful evaluation of knee injuries is necessary. Vascular compromise may also complicate joint replacement surgery. These complications are preventable, and management is greatly simplified by a detailed preoperative evaluation.

  12. Intestinal vascular anomalies in children. (United States)

    Frémond, B; Yazbeck, S; Dubois, J; Brochu, P; Garel, L; Ouimet, A


    Vascular anomalies are an uncommon cause of gastrointestinal bleeding in childhood. Confusing nomenclature has made objective comparisons of published cases difficult and has interfered with an established consensus regarding diagnosis and therapeutic modalities. The purpose of this study was to clarify the situation by reviewing the records of all children who had intestinal vascular anomalies who were referred to our institution from 1975 to 1995. Thirteen lesions were identified in nine children (five boys and four girls). The median age at clinical onset was 8 years. Only two patients presented with a complex syndrome (Klippel-Trenaunay, 1; Osler-Rendu-Weber, 1). Diagnosis, location, and extension of these anomalies was only possible by angiography, which indicated that seven patients had isolated venous malformations and two had arteriovenous malformations. Because the lesions did not involve the serosa, intraoperative localization was a major problem. The main findings were a few slightly dilated mesenteric veins. Treatment was conservative in four children and surgical in five. Pathological findings on resected bowel demonstrated dilated and abnormal veins in the mucosa and submucosa. Selective angiography should not be delayed in patients with gastrointestinal bleeding if results of all other investigations are negative. Because these lesions are rarely recognizable on operative inspection, precise preoperative angiographic localization of intestinal vascular anomalies is essential to allow for a safe and limited resection of the involved bowel segment. Based on a better understanding of the natural history of these lesions, a classification of vascular anomalies of intestines in children is proposed.

  13. Markers of Early Vascular Ageing. (United States)

    Kotsis, Vasilios; Antza, Christina; Doundoulakis, Ioannis; Stabouli, Stella


    Cardiovascular damage is clinically manifested as coronary artery disease, heart failure, stroke and peripheral artery disease. The prevalence of these adverse conditions is higher with advancing age. Although many patients present cardiovascular damage late in their life, it is common to see patients with early atherosclerosis in cardiovascular intensive care units at ages lower than 50 years in men and 55 for women. In this review of the literature we identified risk factors of early vascular damage. The classic risk factors such as age, gender, diabetes mellitus, dyslipidemia, smoking, alcohol, hypertension, obesity, family history and newer biomarkers such as hs-CRP, folic acid, homocysteine, fibrinogen are neither strong nor predictive of the individual patient's risk to present early cardiovascular disease. All these risk factors have been used to propose risk scores for possible future events but we still lack a single strong marker indicating new onset of disease that will predict the future independently of the classical factors. The role of vascular imaging techniques to identify patients with subclinical atherosclerotic vascular damage before clinical disease, including the effect of known and unknown risk factors on the vascular tree, seems to be very important for intensifying preventive measures in high risk patients. Early arteriosclerosis measured from pulse wave velocity is associated with reduced arterial elasticity and is associated with future cardiovascular events. Vascular measurements may better represent the continuum of cardiovascular disease from a young healthy to an aged diseased vessel that is going to produce adverse clinical events. Copyright© Bentham Science Publishers; For any queries, please email at

  14. Pediatric central nervous system vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Ezra A. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Orbach, Darren B. [Boston Children' s Hospital, Neurointerventional Radiology, Boston, MA (United States)


    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  15. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.


    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions.

  16. ESRD QIP - Vascular Access - Payment Year 2018 (United States)

    U.S. Department of Health & Human Services — This dataset includes facility details, performance rates, vascular access topic measure score, and the state and national average measure scores for the vascular...


    African Journals Online (AJOL)



    Dec 1, 2000 ... Results: Road traffic accidents were the main cause of fractures associated with neuro- vascular ... the patients with vascular or nerve injury associated with fractures .... of traumatic aorto-iliac dissection injury in a child with.

  18. Getting into the brain: approaches to enhance brain drug delivery. (United States)

    Patel, Mayur M; Goyal, Bhoomika R; Bhadada, Shraddha V; Bhatt, Jay S; Amin, Avani F


    .g. liposomes, microspheres, nanoparticles, nanogels and bionanocapsules) have been used to enhance drug delivery to the brain. Recently, microchips and biodegradable polymers have become important in brain tumour therapy.The intense search for alternative routes of drug delivery (e.g. intranasal drug delivery, convection-enhanced diffusion and intrathecal/intraventricular drug delivery systems) has been driven by the need to overcome the physiological barriers of the brain and to achieve high drug concentrations within the brain. For more than 30 years, considerable efforts have been made to enhance the delivery of therapeutic molecules across the vascular barriers of the CNS. The current challenge is to develop drug delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner.

  19. Regional Shelter Analysis Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Dillon, Michael B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dennison, Deborah [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kane, Jave [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Walker, Hoyt [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Miller, Paul [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    The fallout from a nuclear explosion has the potential to injure or kill 100,000 or more people through exposure to external gamma (fallout) radiation. Existing buildings can reduce radiation exposure by placing material between fallout particles and exposed people. Lawrence Livermore National Laboratory was tasked with developing an operationally feasible methodology that could improve fallout casualty estimates. The methodology, called a Regional Shelter Analysis, combines the fallout protection that existing buildings provide civilian populations with the distribution of people in various locations. The Regional Shelter Analysis method allows the consideration of (a) multiple building types and locations within buildings, (b) country specific estimates, (c) population posture (e.g., unwarned vs. minimally warned), and (d) the time of day (e.g., night vs. day). The protection estimates can be combined with fallout predictions (or measurements) to (a) provide a more accurate assessment of exposure and injury and (b) evaluate the effectiveness of various casualty mitigation strategies. This report describes the Regional Shelter Analysis methodology, highlights key operational aspects (including demonstrating that the methodology is compatible with current tools), illustrates how to implement the methodology, and provides suggestions for future work.

  20. Appraising Healthcare Delivery Provision: A Framework to Model Business Processes. (United States)

    Luzi, Daniela; Pecoraro, Fabrizio; Tamburis, Oscar


    Children are dependent on a reliable healthcare system, especially for the delivery of care which crosses the primary/secondary care boundary. A methodology based on UML has been developed to capture and single out meaningful parts of the child healthcare pathways in order to facilitate comparison among 30 EU countries within the MOCHA project. A first application of this methodology has been reported considering asthma management as an example.

  1. Self-management of vascular risk factors


    Sol-de Rijk, B.G.M.


    Summary The aim of this thesis was to provide insight into the potential of a self-management approach in treatment of vascular risk factors and to develop a self-management intervention. Furthermore to examine if this intervention, based on self-efficacy promoting theory, is effective in reducing vascular risk factors in patients with established vascular diseases. Patients with different manifestations of vascular diseases appeared to have high levels of self-efficacy concerning the self-ma...

  2. Vascular smooth muscle function: defining the diabetic vascular phenotype. (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo


    In this issue of Diabetologia, a meta-analysis performed by Montero and co-authors (Diabetologia doi 10.1007/s00125-013-2974-1 ) demonstrates a significant impairment of vascular smooth muscle (VSM) function in type 2 diabetic patients. Endothelial function and VSM function between type 2 diabetic and healthy individuals were associated, especially in the microcirculation, confirming the hypothesis that unresponsiveness of VSM cells to NO may amplify the consequences of reduced NO availability. This study suggests a novel interpretation for endothelial dysfunction in diabetic patients, indicating VSM cells as key players. Causative mechanisms of VSM dysfunction, which seems to be a feature of the vascular phenotype of type 2 diabetes mellitus, are largely unexplored in humans. Future studies should also address the crucial issue of the prognostic significance of VSM dysfunction in diabetic patients, and possibly in other conditions characterised by high cardiovascular risk.

  3. Specificity of haemostasis abnormalities for vascular phenotypes. (United States)

    Lowe, G D; Haverkate, F


    Atherothrombosis is a systemic disease, hence it is difficult to prove the specificity of haemostasis abnormality for any single vascular phenotype. Associations between haemostatic variables and any given phenotype, e.g. (vascular) dementia, should be interpreted with caution, given the overlaps of vascular disease phenotypes, risk factors, and haemostatic variables.

  4. 21 CFR 870.4450 - Vascular clamp. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vascular clamp. 870.4450 Section 870.4450 Food and... CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4450 Vascular clamp. (a) Identification. A vascular clamp is a surgical instrument used to occlude a blood vessel temporarily. (b) Classification. Class II...

  5. Hippocampal atrophy in subcortical vascular dementia

    NARCIS (Netherlands)

    van de Pol, L.A.; Gertz, H.J.; Scheltens, P.; Wolf, H


    Background and Purpose: New research criteria for subcortical vascular dementia (SVaD) have been suggested to define a more homogeneous subgroup of vascular dementia. Hippocampal (Hc) atrophy is a hallmark of Alzheimer's disease (AD), but it also occurs in other dementia disorders including vascular

  6. Breastfeeding After Cesarean Delivery (United States)

    ... Stages Listen Español Text Size Email Print Share Breastfeeding After Cesarean Delivery Page Content Article Body A ... delivered vaginally. It is especially important to begin breastfeeding as soon as you are able and to ...

  7. Co-culture systems for vascularization--learning from nature. (United States)

    Kirkpatrick, C James; Fuchs, Sabine; Unger, Ronald E


    The endothelial cell (EC) is practically ubiquitous in the human body and forms the inner cellular lining of the entire cardiovascular system. Following tissue injury, the microcirculation becomes the stage for both the inflammatory response and the subsequent healing reaction to restore physiological function to the damaged tissue. The advent of the multidisciplinary field of Regenerative Medicine (RegMed), of which Tissue Engineering (TE) and drug delivery using modern stimuli-responsive or interactive biomaterials are important components, has opened up new approaches to the acceleration of the healing response. A central and rate-limiting role in the latter is played by the process of vascularization or neovascularization, so that it is not surprising that in RegMed concepts have been developed for the drug- and gene-delivery of potent stimuli such as vascular-endothelial growth factor (VEGF) to promote neovessel development. However, not all of these novel materials can be tested in vivo, and in vitro co-culture model systems using human primary cells are being developed to pre-evaluate and determine which of the RegMed concepts exhibit the most promising potential for success after implantation. This review describes some of the growing number of in vitro co-cultures model systems that are being used to study cell-cell and cell-material interactions at the cellular and molecular levels to determine which materials are best suited to integrate into the host, promote a rapid vascularization and fit into the regenerative process without disturbing or slowing the normal healing steps. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Creativity in phenomenological methodology

    DEFF Research Database (Denmark)

    Dreyer, Pia; Martinsen, Bente; Norlyk, Annelise


    on the methodologies of van Manen, Dahlberg, Lindseth & Norberg, the aim of this paper is to argue that the increased focus on creativity and arts in research methodology is valuable to gain a deeper insight into lived experiences. We illustrate this point through examples from empirical nursing studies, and discuss......Nursing research is often concerned with lived experiences in human life using phenomenological and hermeneutic approaches. These empirical studies may use different creative expressions and art-forms to describe and enhance an embodied and personalised understanding of lived experiences. Drawing...... may support a respectful renewal of phenomenological research traditions in nursing research....

  9. Changing methodologies in TESOL

    CERN Document Server

    Spiro, Jane


    Covering core topics from vocabulary and grammar to teaching, writing speaking and listening, this textbook shows you how to link research to practice in TESOL methodology. It emphasises how current understandings have impacted on the language classroom worldwide and investigates the meaning of 'methods' and 'methodology' and the importance of these for the teacher: as well as the underlying assumptions and beliefs teachers bring to bear in their practice. By introducing you to language teaching approaches, you will explore the way these are influenced by developments in our understanding of l

  10. Temporal Multiscale Approach for Nanocarrier Motion with Simultaneous Adhesion and Hydrodynamic Interactions in Targeted Drug Delivery (United States)

    Radhakrishnan, R.; Uma, B.; Liu, J.; Ayyaswamy, P. S.; Eckmann, D. M.


    We present a fluctuating hydrodynamics approach and a hybrid approach combining fluctuating hydrodynamics with generalized Langevin dynamics to resolve the motion of a nanocarrier when subject to both hydrodynamic interactions and adhesive interactions. Specifically, using these approaches, we compute equilibrium probability distributions at constant temperature as well as velocity autocorrelation functions of the nanocarrier subject to thermal motion in a quiescent Newtonian fluid medium, when tethered by a harmonic spring force mimicking a tether due to a single receptor-ligand bond. We demonstrate that the thermal equipartition of translation, rotation, and spring degrees of freedom are preserved by our formalism while simultaneously resolving the nature of the hydrodynamic correlations. Additionally, we evaluate the potential of mean force (or free energy density) along a specified reaction coordinate to faciltate extensive conformational sampling of the nanocarrier motion. We show that our results are in excellent agreement with analytical results and Monte Carlo simulations, thereby validating our methodologies. The frameworks we have presented provide a comprehensive platform for temporal multiscale modeling of hydrodynamic and microscopic interactions mediating nanocarrier motion and adhesion in vascular targeted drug delivery. PMID:23853388

  11. Near-infraread spectroscopy during peripheral vascular surgery

    DEFF Research Database (Denmark)

    Schroeder, Torben Veith; Eiberg, Jonas Peter; Vogt, Katja


    Original,Near-infraread spectroscopy,Vascular disease,Vascular by-pass surgery,Perioperative oxymetry......Original,Near-infraread spectroscopy,Vascular disease,Vascular by-pass surgery,Perioperative oxymetry...

  12. Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact. (United States)

    Takara, Kazuhiro; Eino, Daisuke; Ando, Koji; Yasuda, Daisuke; Naito, Hisamichi; Tsukada, Yohei; Iba, Tomohiro; Wakabayashi, Taku; Muramatsu, Fumitaka; Kidoya, Hiroyasu; Fukuhara, Shigetomo; Mochizuki, Naoki; Ishii, Satoshi; Kishima, Haruhiko; Takakura, Nobuyuki


    Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6). In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact

    Directory of Open Access Journals (Sweden)

    Kazuhiro Takara


    Full Text Available Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1–6. In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation.

  14. Courseware Engineering Methodology. (United States)

    Uden, Lorna


    Describes development of the Courseware Engineering Methodology (CEM), created to guide novices in designing effective courseware. Discusses CEM's four models: pedagogical (concerned with the courseware's pedagogical aspects), conceptual (dealing with software engineering), interface (relating to human-computer interaction), and hypermedia…

  15. The methodological cat

    Directory of Open Access Journals (Sweden)

    Marin Dinu


    Full Text Available Economics understands action as having the connotation of here and now, the proof being that it excessively uses, for explicative purposes, two limitations of sense: space is seen as the place with a private destination (through the cognitive dissonance of methodological individualism, and time is seen as the short term (through the dystopia of rational markets.

  16. Methodological Advances in Dea

    NARCIS (Netherlands)

    L. Cherchye (Laurens); G.T. Post (Thierry)


    textabstractWe survey the methodological advances in DEA over the last 25 years and discuss the necessary conditions for a sound empirical application. We hope this survey will contribute to the further dissemination of DEA, the knowledge of its relative strengths and weaknesses, and the tools

  17. Gravitational constant calculation methodologies


    Shakhparonov, V. M.; Karagioz, O. V.; Izmailov, V. P.


    We consider the gravitational constant calculation methodologies for a rectangular block of the torsion balance body presented in the papers Phys. Rev. Lett. 102, 240801 (2009) and Phys.Rev. D. 82, 022001 (2010). We have established the influence of non-equilibrium gas flows on the obtained values of G.

  18. A Functional HAZOP Methodology

    DEFF Research Database (Denmark)

    Liin, Netta; Lind, Morten; Jensen, Niels


    and investigated in a HAZOP study of an industrial scale Indirect Vapor Recompression Distillation pilot Plant (IVaRDiP) at DTU-Chemical and Biochemical Engineering. The study shows that the functional HAZOP methodology provides a very efficient paradigm for facilitating HAZOP studies and for enabling reasoning...... to reveal potential hazards in safety critical operations....

  19. [Menopause: Hypertension and vascular disease]. (United States)

    Zilberman, J M


    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Endovascular aneurysm repair delivery redesign leads to quality improvement and cost reduction. (United States)

    Warner, Courtney J; Horvath, Alexander J; Powell, Richard J; Columbo, Jesse A; Walsh, Teri R; Goodney, Philip P; Walsh, Daniel B; Stone, David H


    Endovascular aneurysm repair (EVAR) is now a mainstay of therapy for abdominal aortic aneurysm, although it remains associated with significant expense. We performed a comprehensive analysis of EVAR delivery at an academic medical center to identify targets for quality improvement and cost reduction in light of impending health care reform. All infrarenal EVARs performed from April 2011 to March 2012 were identified (N = 127). Procedures were included if they met standard commercial instructions for use guidelines, used a single manufacturer, and were billed to Medicare diagnosis-related group 238 (n = 49). By use of DMAIC (define, measure, analyze, improve, and control) quality improvement methodology (define, measure, analyze, improve, control), targets for EVAR quality improvement were identified and high-yield changes were implemented. Procedure technical costs were calculated before and after process redesign. Perioperative services and clinic visits were identified as targets for quality improvement efforts and cost reduction. Mean technical costs before the intervention were $31,672, with endograft implants accounting for 52%. Pricing redesign in collaboration with hospital purchasing reduced mean EVAR technical costs to $28,607, a 10% reduction in overall cost, with endograft implants now accounting for 46%. Perioperative implementation of instrument tray redesign reduced instrument use by 32% (184 vs 132 instruments), saving $50,000 annually. Unnecessary clinic visits were reduced by 39% (1.6 vs 1.1 clinic visits per patient) through implementation of a preclinic imaging protocol. There was no difference in mean length of stay after the intervention. Comprehensive EVAR delivery redesign leads to cost reduction and waste elimination while preserving quality. Future efforts to achieve more competitive and transparent device pricing will make EVAR more cost neutral and enhance its financial sustainability for health care systems. Copyright © 2015 Society for

  1. Angiogenesis, Cancer, and Vascular Aging


    Junji Moriya; Tohru Minamino


    Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD) among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging o...

  2. Vascular Aging and Arterial Stiffness

    Directory of Open Access Journals (Sweden)

    Luana de Rezende Mikael

    Full Text Available Abstract Cardiovascular diseases (CVD account annually for almost one third of all deaths worldwide. Among the CVD, systemic arterial hypertension (SAH is related to more than half of those outcomes. Type 2 diabetes mellitus is an independent risk factor for SAH because it causes functional and structural damage to the arterial wall, leading to stiffness. Several studies have related oxidative stress, production of free radicals, and neuroendocrine and genetic changes to the physiopathogenesis of vascular aging. Indirect ways to analyze that aging process have been widely studied, pulse wave velocity (PWV being considered gold standard to assess arterial stiffness, because there is large epidemiological evidence of its predictive value for cardiovascular events, and it requires little technical knowledge to be performed. A pulse wave is generated during each cardiac contraction and travels along the arterial bed until finding peripheral resistance or any bifurcation point, determining the appearance of a reflected wave. In young individuals, arteries tend to be more elastic, therefore, the reflected wave occurs later in the cardiac cycle, reaching the heart during diastole. In older individuals, however, the reflected wave occurs earlier, reaching the heart during systole. Because PWV is an important biomarker of vascular damage, highly valuable in determining the patient’s global cardiovascular risk, we chose to review the articles on vascular aging in the context of cardiovascular risk factors and the tools available to the early identification of that damage.

  3. Risk assessment, risk management, and prevention of acute vascular events

    Directory of Open Access Journals (Sweden)

    Gundu H R Rao


    Full Text Available South Asians have a very high incidence of cardiometabolic diseases such as hypertension, central abdominal obesity, metabolic syndrome, type 2 diabetes, heart disease, and stroke. In spite of the fact that common risk factors associated with these clinical conditions are known, we do not have point-of-care assays, to monitor the disease of the vessels, and the efficacy of antiplatelet therapy. We have a window of opportunity to develop three-dimensional ultrasound methodologies, to monitor the subclinical atherosclerosis, altered flow velocities of regional vascular beds, as well as plaque progression and regression in the major vessels. We also have opportunities to develop state-of-the-art methodologies for monitoring the efficacy or otherwise of antiplatelet therapies. In this overview, we share our views and strategies for the development of affordable medical technologies in India, for monitoring vessel wall pathology as well as for better management of antiplatelet therapies.

  4. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone delivery. Keywords: Transdermal, Delivery systems, ... delivery compared with gels, emulsions, patches, and subcutaneous implants. Among .... In a safety announcement, the US Food and. Drug Administration (FDA) warned that ...

  5. Vascularization regenerative medicine and tissue engineering

    CERN Document Server

    Brey, Eric M


    A Complex and Growing Field The study of vascularization in tissue engineering and regenerative medicine (TERM) and its applications is an emerging field that could revolutionize medical approaches for organ and tissue replacement, reconstruction, and regeneration. Designed specifically for researchers in TERM fields, Vascularization: Regenerative Medicine and Tissue Engineering provides a broad overview of vascularization in TERM applications. This text summarizes research in several areas, and includes contributions from leading experts in the field. It defines the difficulties associated with multicellular processes in vascularization and cell-source issues. It presents advanced biomaterial design strategies for control of vascular network formation and in silico models designed to provide insight not possible in experimental systems. It also examines imaging methods that are critical to understanding vascularization in engineered tissues, and addresses vascularization issues within the context of specific...

  6. Quantifying three-dimensional rodent retina vascular development using optical tissue clearing and light-sheet microscopy (United States)

    Singh, Jasmine N.; Nowlin, Taylor M.; Seedorf, Gregory J.; Abman, Steven H.; Shepherd, Douglas P.


    Retinal vasculature develops in a highly orchestrated three-dimensional (3-D) sequence. The stages of retinal vascularization are highly susceptible to oxygen perturbations. We demonstrate that optical tissue clearing of intact rat retinas and light-sheet microscopy provides rapid 3-D characterization of vascular complexity during retinal development. Compared with flat mount preparations that dissect the retina and primarily image the outermost vascular layers, intact cleared retinas imaged using light-sheet fluorescence microscopy display changes in the 3-D retinal vasculature rapidly without the need for point scanning techniques. Using a severe model of retinal vascular disruption, we demonstrate that a simple metric based on Sholl analysis captures the vascular changes observed during retinal development in 3-D. Taken together, these results provide a methodology for rapidly quantifying the 3-D development of the entire rodent retinal vasculature.

  7. Methods and metrics challenges of delivery-system research

    Directory of Open Access Journals (Sweden)

    Alexander Jeffrey A


    Full Text Available Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned. This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1 modeling intervention context; (2 measuring readiness for change; (3 assessing intervention fidelity and sustainability; (4 assessing complex, multicomponent interventions; and (5 incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ, US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on

  8. Novel Synergistic Therapy for Metastatic Breast Cancer: Magnetic Nanoparticle Hyperthermia of the Neovasculature Enhanced by a Vascular Disruption Agent (United States)


    Delivery Female NOD-SCID mice were bred at the University of New Mexico Animal Resource Facility. All mouse procedures were performed according to...Imaging of Vascular Endothelial Growth Factor Receptor 2 Expression Using Targeted Contrast-Enhanced High-Frequency Ultrasonography . J Ultrasound Med

  9. Vascular risk factors as treatment target to prevent cognitive decline. (United States)

    Richard, Edo; Moll van Charante, Eric P; van Gool, Willem A


    Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies have confirmed the importance of cerebrovascular lesions in the etiology of late onset dementia. We have reviewed the literature and conclude that up until now randomized controlled clinical trials targeting individual risk factors and assessing cognitive decline or dementia as an outcome have not convincingly shown that treatment of vascular risk factors can actually prevent or postpone cognitive decline and dementia. New studies targeting several vascular risk factors at the same time and using cognitive decline or dementia as primary outcome might answer the question whether cognitive decline can really be postponed or even prevented. The design of such studies is not straightforward and long follow-up is required. In this review we discuss several pertinent methodological issues that need to be addressed to achieve an optimal design of new randomized controlled trials.

  10. Impact of delivery mode on the colostrum microbiota composition. (United States)

    Toscano, Marco; De Grandi, Roberta; Peroni, Diego Giampietro; Grossi, Enzo; Facchin, Valentina; Comberiati, Pasquale; Drago, Lorenzo


    Breast milk is a rich nutrient with a temporally dynamic nature. In particular, numerous alterations in the nutritional, immunological and microbiological content occur during the transition from colostrum to mature milk. The objective of our study was to evaluate the potential impact of delivery mode on the microbiota of colostrum, at both the quantitative and qualitative levels (bacterial abundance and microbiota network). Twenty-nine Italian mothers (15 vaginal deliveries vs 14 Cesarean sections) were enrolled in the study. The microbiota of colostrum samples was analyzed by next generation sequencing (Ion Torrent Personal Genome Machine). The colostrum microbiota network associated with Cesarean section and vaginal delivery was evaluated by means of the Auto Contractive Map (AutoCM), a mathematical methodology based on Artificial Neural Network (ANN) architecture. Numerous differences between Cesarean section and vaginal delivery colostrum were observed. Vaginal delivery colostrum had a significant lower abundance of Pseudomonas spp., Staphylococcus spp. and Prevotella spp. when compared to Cesarean section colostrum samples. Furthermore, the mode of delivery had a strong influence on the microbiota network, as Cesarean section colostrum showed a higher number of bacterial hubs if compared to vaginal delivery, sharing only 5 hubs. Interestingly, the colostrum of mothers who had a Cesarean section was richer in environmental bacteria than mothers who underwent vaginal delivery. Finally, both Cesarean section and vaginal delivery colostrum contained a greater number of anaerobic bacteria genera. The mode of delivery had a large impact on the microbiota composition of colostrum. Further studies are needed to better define the meaning of the differences we observed between Cesarean section and vaginal delivery colostrum microbiota.

  11. Tobacco documents research methodology. (United States)

    Anderson, Stacey J; McCandless, Phyra M; Klausner, Kim; Taketa, Rachel; Yerger, Valerie B


    Tobacco documents research has developed into a thriving academic enterprise since its inception in 1995. The technology supporting tobacco documents archiving, searching and retrieval has improved greatly since that time, and consequently tobacco documents researchers have considerably more access to resources than was the case when researchers had to travel to physical archives and/or electronically search poorly and incompletely indexed documents. The authors of the papers presented in this supplement all followed the same basic research methodology. Rather than leave the reader of the supplement to read the same discussion of methods in each individual paper, presented here is an overview of the methods all authors followed. In the individual articles that follow in this supplement, the authors present the additional methodological information specific to their topics. This brief discussion also highlights technological capabilities in the Legacy Tobacco Documents Library and updates methods for organising internal tobacco documents data and findings.

  12. 1. Methodological Questions

    Directory of Open Access Journals (Sweden)

    Luca Arcari (a cura di


    Full Text Available The first part of this monographic section aims at analysing some methodological questions concerning identities, ethnicities, collectivities and religions, starting from the academic debate occurred between historians and anthropologists since the last decades of Twentieth Century, considering its reception especially for the study of ethnicity and collective and/or (so-called religious identities in the cultural context of ancient Greece. Another aspect of such a methodological section deals with the innovative approach inaugurated by the so-called “School of Wien” in the study of ethnic identity-constructions, especially analysing the relationships with Biblical texts as well as their multiform receptions between late-antiquity and early medieval period.

  13. [Methodological currents in research]. (United States)

    Angerami, E L


    Believing that research is the academic activity which gives support to assistance and teaching in nursing and this activity represents a process of knowledge construction which follows determined patterns, the authors try to enhance reflection on the importance of methodology matters to nursing. The study proposes three patterns of contact between subject and object: the positivist approach, the comprehensive approach and the dialectical approach, most frequent philosophical streams in health studies.

  14. Presymptomatic genetic analysis during pregnancy for vascular type Ehlers–Danlos syndrome (United States)

    Naing, Banyar Than; Watanabe, Atsushi; Tanigaki, Shinji; Ono, Masae; Iwashita, Mitsutoshi; Shimada, Takashi


    The vascular type of Ehlers–Danlos syndrome (EDS), EDS type IV (Online Mendelian Inheritance in Man [MIM] #130050) is characterized by thin, translucent skin, easy bruising, and arterial, intestinal, and/or uterine fragility during pregnancy, which may lead to sudden death. It is an autosomal dominant inherited disorder caused by type III procollagen gene (COL3A1: MIM #120180) mutations. Approximately 50% of the COL3A1 mutations are inherited from an affected parent, and 50% are de novo mutations. Each child of an affected individual has a 50% chance of inheriting the mutation and developing the disorder. Pregnant women with vascular EDS are at an increased risk of uterine and arterial rupture during the peripartum period, with high maternal morbidity and mortality rates. We report the first case of an asymptomatic 35-year-old woman at a risk of complications of vascular EDS who underwent presymptomatic evaluation during pregnancy. The sequencing results of both her brother and mother had a one-base-pair deletion, resulting in Glutamate at position 730 changing to Lysine and causing a frame shift and premature termination codon at 61 amino acids from the mutation position (p. Glu730Lysfs*61) on exon 32 of COL3A1. This deletion caused frameshift, leading to a premature termination codon (TAG) at 181 nucleotides downstream in exon 35, which could not be detected by previous total RNA (ribonucleic acid) method. Thus, she was at risk of complications of vascular EDS, and diagnostic testing was employed at 8 weeks of pregnancy to minimize the risk of developing vascular EDS-related complications. The negative presymptomatic diagnostic result allowed the patient to choose normal delivery at term. Vascular EDS is a serious disorder, with high mortality, especially in high-risk women with vascular EDS during pregnancy. The presymptomatic genetic testing of vascular EDS during pregnancy for a high-risk family can help with the early establishment of preventive measures

  15. Intravenous delivery of adenovirus-mediated soluble FLT-1 results in liver toxicity

    NARCIS (Netherlands)

    Mahasreshti, P.J.; Kataram, M.; Wang, Ming H.; Stockard, C.R.; Grizzle, W.E.; Carey, D.; Siegal, G.P.; Haisma, H.J.; Alvarez, R.D.; Curiel, D.T.

    Purpose: Vascular endothelial growth factor (VEGF) is a potent angiogenic agent and plays a major role in tumor growth and metastases. We have previously reported the locoregional (i.p.) delivery of adenovirus-mediated antiangiogenic soluble FLT-1 (sFLT-1; a naturally encoded potent VEGF antagonist)

  16. Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery

    NARCIS (Netherlands)

    Christensen, Lane V.; Christensen, L.; Chang, Chien-Wen; Yockman, James W.; Conners, Rafe; Jackson, Heidi; Zhong, Zhiyuan; Feijen, Jan; Bull, David A.; Kim, Sung Wan


    Delivery of the hypoxia-inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted

  17. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush

    We investigate antecedents and contingencies of location configurations supporting global delivery models (GDMs) in global outsourcing. GDMs are a new form of IT-enabled client-specific investment promoting services provision integration with clients by exploiting client proximity and time-zone s...... commoditized. Findings imply that coordination across time zones increasingly affects international operations in business-to-business and born-global industries.......We investigate antecedents and contingencies of location configurations supporting global delivery models (GDMs) in global outsourcing. GDMs are a new form of IT-enabled client-specific investment promoting services provision integration with clients by exploiting client proximity and time-zone...

  18. Ghrelin improves vascular autophagy in rats with vascular calcification. (United States)

    Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan


    This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effect of vascular burden as measured by vascular indexes upon vascular dementia: a matched case-control study


    Takahashi, Paul Y; Caldwell, Casey R; Targonski, Paul V


    Paul Y Takahashi, Casey R Caldwell, Paul V TargonskiPrimary Care Internal Medicine, Mayo Clinic, Rochester MN, USABackground: Vascular dementia (VaD) is a challenging illness that affects the lives of older adults and caregivers. It is unclear how multiple vascular risk factor exposures (polyvascular disease) affect VaD.Purpose: To determine the relationship between multiple vascular risk exposures, as counted on an index in cases with VaD, compared with healthy age-/gender-matched controls.M...

  20. Bioinspired Nanonetworks for Targeted Cancer Drug Delivery. (United States)

    Raz, Nasibeh Rady; Akbarzadeh-T, Mohammad-R; Tafaghodi, Mohsen


    A biomimicry approach to nanonetworks is proposed here for targeted cancer drug delivery (TDD). The swarm of bioinspired nanomachines utilizes the blood distribution network and chemotaxis to carry drug through the vascular system to the cancer site, recognized by a high concentration of vascular endothelial growth factor (VEGF). Our approach is multi-scale and includes processes that occur both within cells and with their neighbors. The proposed bionanonetwork takes advantage of several organic processes, some of which already occur within the human body, such as a plate-like structure similar to those of red blood cells for more environmental contact; a berry fruit architecture for its internal multi-foams architecture; the penetrable structure of cancer cells, tissue, as well as the porous structure of the capillaries for drug penetration; state of glycocalyx for ligand-receptor adhesion; as well as changes in pH state of blood and O 2 release for nanomachine communication. For a more appropriate evaluation, we compare our work with a conventional chemotherapy approach using a mathematical model of cancer under actual experimental parameter settings. Simulation results show the merits of the proposed method in targeted cancer therapy by improving the densities of the relevant cancer cell types and VEGF concentration, while following more organic and natural processes.

  1. Vascular dementia: Facts and controversies

    Directory of Open Access Journals (Sweden)

    Pavlović Aleksandra


    Full Text Available Vascular dementia (VaD is the second most frequent dementia after Alzheimer’s disease, and is diagnosed during lifetime in 20% of demented patients. Five­year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors for VaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step­by­step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class IIa recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer’s disease dementia. [Projekat Ministarstva nauke Republike Srbije, br. 175022 i br. 175033


    Directory of Open Access Journals (Sweden)

    Donata eGuidetti


    Full Text Available Several comorbidities are associated to migraine.Recent meta-analyses have consistently demonstrated a relationship between migraine and stroke, which is well-defined for ischaemic stroke and migraine with aura, even stronger in females on oral contraceptives or smokers. However, there seems to be no clear-cut association between stroke in migraineurs and the common vascular risk factors, at least in the young adult population. Migraineurs also run an increased risk of hemorrhagic stroke, while the association between migraine and cardiovascular disease remains poorly defined.Another aspect is the relationship between migraine and the presence of silent brain lesions. It has been demonstrated that there is an increased frequency of ischaemic lesions in the white matter of migraineurs, especially silent infarcts in the posterior circulation territory in patients with at least 10 attacks per month. Although there is a higher prevalence of patent foramen ovale (PFO in migraineurs, the relationship between migraine and PFO remains controversial and PFO closure is not a recommended procedure to prevent migraine. As an increased frequency of cervical artery dissections has been observed in migrainous patients, it has been hypothesized that migraine may represent a predisposing factor for cervical artery dissection. There still remains the question as to whether migraine should be considered a true vascular disease or if the comorbidity between migraine and cerebrovascular disease may have underlying shared risk factors or pathophysiological mechanisms. Although further studies are required to clarify this issue, current evidence supports a clinical management where MA patients should be screened for other concomitant vascular risk factors and treated accordingly.

  3. Harnessing Electrostatic Forces to Grow Bio-inspired Hierarchical Vascular Networks (United States)

    Behler, Kristopher; Melrose, Zachary; Schott, Andrew; Wetzel, Eric


    Vascular networks provide a system for fluid distribution. Artificial vascular materials with enhanced properties are currently being developed that could ultimately be integrated into systems reliant upon fluid transport while retaining their structural properties. An uninterrupted and controllable supply of liquid is optimal for many applications such as continual self-healing materials, in-situ delivery of index matched fluids, thermal management and drug delivery systems could benefit from a bio-inspired vascular approach that combines complex network geometries with minimal processing parameters. Two such approaches to induce vascular networks are electrohydrodynamic viscous fingering (EHVF) and electrical treeing (ET). EHVF is a phenomenon that occurs when a low viscosity liquid is forced through a high viscosity fluid or matrix, resulting in branches due to capillary and viscous forces in the high viscosity material. By applying voltages of 0 -- 60 kV, finger diameter is reduced. ET is the result of partial discharges in a dielectric material. In the vicinity of a small diameter electrode, the local electric field is greater than the global dielectric strength, causing a localized, step-wise, breakdown to occur forming a highly branched interconnected structure. ET is a viable method to produce networks on a smaller, micron, scale than the products of the EHVF method.

  4. Spinal vascular malformations; Spinale Gefaessmalformationen

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, U. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)


    Spinal vascular malformations are a group of rare diseases with different clinical presentations ranging from incidental asymptomatic findings to progressive tetraplegia. This article provides an overview about imaging features as well as clinical and therapeutic aspects of spinal arteriovenous malformations, cavernomas and capillary telangiectasia. (orig.) [German] Spinale Gefaessmalformationen sind eine Gruppe seltener Erkrankungen mit unterschiedlichen klinischen Praesentationen, die vom asymptomatischen Zufallsbefund bis zur progredienten Tetraparese reichen. Dieser Artikel gibt einen Ueberblick ueber radiologische Befunde sowie klinische und therapeutische Aspekte von spinalen arteriovenoesen Malformationen, Kavernomen und kapillaeren Teleangiektasien. (orig.)

  5. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils


    To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case–control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980–2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

  6. Exploring educational disparities in risk of preterm delivery

    DEFF Research Database (Denmark)

    Poulsen, Gry; Strandberg-Larsen, Katrine; Mortensen, Laust


    BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort...... data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks...... of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal...

  7. Methodology applied to develop the DHIE: applied methodology

    CSIR Research Space (South Africa)

    Herselman, Marlien


    Full Text Available This section will address the methodology that was applied to develop the South African Digital Health Innovation Ecosystem (DHIE). Each chapter under Section B represents a specific phase in the methodology....

  8. [Vascular depression, limits of the concept]. (United States)

    Lebert, Florence


    The concept of vascular depression has recently been reassessed and more clearly delineated. The diagnostic criteria for vascular depression require a major depression associated with evidence of confluent or diffuse vascular lesions in the subcortical regions on MRI. The clinical symptoms are not specific, but they are often associated with mild cognitive decline. Ischemia is probably the main factor for vascular depression, but the relationship between ischemic lesions and clinical symptoms remains not well explained. The apolipoproteine E genotype is not a risk factor for vascular depression, but it is associated with more severe hyperintensities on MRI. A pharmacological resistance has been described in vascular depression, but, in recent studies, clinical improvement has been observed with antidepressants in more than 80% of cases. A neuropsychological follow-up is recommended, because dementia may appear with 25% of patients.

  9. Protecting against vascular disease in brain (United States)


    Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

  10. A Medical Delivery Device

    DEFF Research Database (Denmark)


    The present invention relates to a medical delivery device comprising at least two membrane electrode assembly units each of which comprises three layers: an upper and a lower electrode and a selective ionic conductive membrane provided there-between. At least one of the three layers are shared...

  11. 6. Home deliveries

    African Journals Online (AJOL)


    using a conceptual framework so as to remove the. 14 possible confounding effect of this on education . Overall, it may not have been surprising that the number of years of schooling for mothers, the household income and distance were significant determinants for home deliveries given that this is plausible. In addition to ...

  12. 6. Home deliveries

    African Journals Online (AJOL)


    PO Box 50110, Lusaka. Telephone: (+260) - 977-248033-mobile;. Telefax (+260) - 211-256181-office. E-mail: Conclusion: The association of home deliveries with access to health care suggests a need for structural response coupled with ethnographic studies to explore linked aspects of traditional.

  13. The Impact of Sociological Methodology on Statistical Methodology


    Clogg, Clifford C.


    Developments in sociological methodology and in quantitative sociology have always been closely related to developments in statistical theory, methodology and computation. The same statement applies if "methodology for social research" and "quantitative social research" replace the more specific terms in this statement. Statistical methodology, including especially the battery of methods used to estimate and evaluate statistical models, has had a tremendous effect on social research in the po...

  14. Differing antidepressant maintenance methodologies. (United States)

    Safer, Daniel J


    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

  15. Vascular adaption to physical inactivity in humans


    Bleeker, M.W.P.


    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical inactivity, exercise decreases the risk for cardiovascular disease. This beneficial effect of exercise is partly due to changes in vascular function and structure. However, far less is known about vascular ...

  16. Sample size methodology

    CERN Document Server

    Desu, M M


    One of the most important problems in designing an experiment or a survey is sample size determination and this book presents the currently available methodology. It includes both random sampling from standard probability distributions and from finite populations. Also discussed is sample size determination for estimating parameters in a Bayesian setting by considering the posterior distribution of the parameter and specifying the necessary requirements. The determination of the sample size is considered for ranking and selection problems as well as for the design of clinical trials. Appropria

  17. SHRS RRCL selection methodology

    Energy Technology Data Exchange (ETDEWEB)

    Trainer, J E; Delaney, H M


    The CRBRP Safety Related Reliability Program requires a listing of those design items whose failure would impact the ability of the plant for a safe shutdown or shutdown heat removal mission. This listing is referred to as the Reliability Related Components List (RRCL) and heretofore, has been based on sound engineering judgement. As a check for completeness and as a means of providing a probabilistic-based rationale for component selection, this report presents a methodology by which this selection can be made for each of the decay heat removal loops comprising the Shutdown Heat Removal System (SHRS) using existing EG and G fault tree models.

  18. Literacy research methodologies

    CERN Document Server

    Duke, Nell K


    The definitive reference on literacy research methods, this book serves as a key resource for researchers and as a text in graduate-level courses. Distinguished scholars clearly describe established and emerging methodologies, discuss the types of questions and claims for which each is best suited, identify standards of quality, and present exemplary studies that illustrate the approaches at their best. The book demonstrates how each mode of inquiry can yield unique insights into literacy learning and teaching and how the methods can work together to move the field forward.   New to This Editi

  19. Enhanced Recovery after Vascular Surgery

    Directory of Open Access Journals (Sweden)

    Milena D. Stojanovic


    Full Text Available The beginnings of the enhanced recovery after surgery (ERAS program were first developed for patients in colorectal surgery, and after it was established as the standard of care in this surgical field, it began to be applied in many others surgical areas. This is multimodal, evidence-based approach program and includes simultaneous optimization of preoperative status of patients, adequate selection of surgical procedure and postoperative management. The aim of this program is to reduce complications, the length of hospital stay and to improve the patients outcome. Over the past decades, special attention was directed to the postoperative management in vascular surgery, especially after major vascular surgery because of the great risk of multiorgan failure, such as: respiratory failure, myocardial infarction, hemodynamic instability, coagulopathy, renal failure, neurological disorders, and intra-abdominal complications. Although a lot of effort was put into it, there is no unique acceptable program for ERAS in this surgical field, and there is still a need to point out the factors responsible for postoperative outcomes of these patients. So far, it is known that special attention should be paid to already existing diseases, type and the duration of the surgical intervention, hemodynamic and fluid management, nutrition, pain management, and early mobilization of patients.

  20. Neuroradiological findings in vascular dementia

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali; Miaux, Yves; Suhy, Joyce; Pauls, Jon; Lopez, Ria [Synarc, Inc., Department of Radiology Services, San Francisco, CA (United States); Rovira-Canellas, Alex [Hospital General Universitari Vall d' Hebron, Unita de Resonancia Magnetica, Barcelona (Spain); Posner, Holly [Eisai, Inc., Teaneck, NJ (United States)


    There are multiple diagnostic criteria for vascular dementia (VaD) that may define different populations. Utilizing the criteria of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) has provided improved consistency in the diagnosis of VaD. The criteria include a table listing brain imaging lesions associated with VaD. The different neuroradiological aspects of the criteria are reviewed based on the imaging data from an ongoing large-scale clinical trial testing a new treatment for VaD. The NINDS-AIREN criteria were applied by a centralized imaging rater to determine eligibility for enrollment in 1,202 patients using brain CT or MRI. Based on the above data set, the neuroradiological features that are associated with VaD and that can result from cerebral small-vessel disease with extensive leukoencephalopathy or lacunae (basal ganglia or frontal white matter), or may be the consequence of single strategically located infarcts or multiple infarcts in large-vessel territories, are illustrated. These features may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage, or other mechanisms such as genetically determined arteriopathies. Neuroimaging confirmation of cerebrovascular disease in VaD provides information about the topography and severity of vascular lesions. Neuroimaging may also assist with the differential diagnosis of dementia associated with normal pressure hydrocephalus, chronic subdural hematoma, arteriovenous malformation or tumoral diseases. (orig.)

  1. Stable vascular connections and remodeling require full expression of VE-cadherin in zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Mercedes Montero-Balaguer

    Full Text Available BACKGROUND: VE-cadherin is an endothelial specific, transmembrane protein, that clusters at adherens junctions where it promotes homotypic cell-cell adhesion. VE-cadherin null mutation in the mouse results in early fetal lethality due to altered vascular development. However, the mechanism of action of VE-cadherin is complex and, in the mouse embryo, it is difficult to define the specific steps of vascular development in which this protein is involved. METHODOLOGY AND PRINCIPAL FINDINGS: In order to study the role VE-cadherin in the development of the vascular system in a more suitable model, we knocked down the expression of the coding gene in zebrafish. The novel findings reported here are: 1 partial reduction of VE-cadherin expression using low doses of morpholinos causes vascular fragility, head hemorrhages and increase in permeability; this has not been described before and suggests that the total amount of the protein expressed is an important determinant of vascular stability; 2 concentrations of morpholinos which abrogate VE-cadherin expression prevent vessels to establish successful reciprocal contacts and, as a consequence, vascular sprouting activity is not inhibited. This likely explains the observed vascular hyper-sprouting and the presence of several small, collapsing vessels; 3 the common cardinal vein lacks a correct connection with the endocardium leaving the heart separated from the rest of the circulatory system. The lack of closure of the circulatory loop has never been described before and may explain some downstream defects of the phenotype such as the lack of a correct vascular remodeling. CONCLUSIONS AND SIGNIFICANCE: Our observations identify several steps of vascular development in which VE-cadherin plays an essential role. While it does not appear to regulate vascular patterning it is implicated in vascular connection and inhibition of sprouting activity. These processes require stable cell-cell junctions which are

  2. Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index. (United States)

    Goto, Toshihiko; Wakami, Kazuaki; Mori, Kento; Kikuchi, Shohei; Fukuta, Hidekatsu; Ohte, Nobuyuki


    Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

  3. Proatherogenic pathways leading to vascular calcification

    Energy Technology Data Exchange (ETDEWEB)

    Mazzini, Michael J. [Department of Cardiology, Boston University Medical Center, Boston, MA (United States); Schulze, P. Christian [Department of Medicine, Boston University Medical Center, Boston, MA (United States)]. E-mail:


    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease.

  4. Vascular tumors and malformations in children, Introduction. (United States)

    Maguiness, Sheilagh M


    Over the past decade, I have been amazed at the growth in the field of vascular anomalies. The recognition of vascular birthmarks as a defined area of medicine is a relatively recent event. The International Society for the Study of Vascular Anomalies (ISSVA) was founded by Drs John Mulliken and Anthony Young in the late 1970s. Mulliken and Glowacki's sentinel 1982 paper on the biologic classification of vascular anomalies further established the field, by providing clarity of nomenclature and unifying concepts that had previously been lacking. ©2016 Frontline Medical Communications.

  5. [Diagnosis and management of vascular anomalies]. (United States)

    Philandrianos, C; Degardin, N; Casanova, D; Petit, P; Bartoli, J-M; Bardot, J; Magalon, G


    Vascular anomalies are a complex pathological group. They are especially difficult to study because of confusion in the terminology used. The classification developed by the International Society for the Study of Vascular Anomalies (ISSVA) in 1996 allows using a common scientific language. There are two groups of lesions: vascular tumor and vascular malformation. The management of these anomalies is difficult and must involve an interdisciplinary approach including specialists in plastic surgery, radiology, pediatry and dermatology. We propose a simplified approach for the management of these pathologies. This approach is coming from the experience of Marseille (France) multidisciplinary team. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  6. Tumor vascular disruption using various radiation types

    Directory of Open Access Journals (Sweden)

    JJ Bevelacqua


    Full Text Available The feasibility of disrupting a tumor’s vascular structure with various radiation types and radionuclides is investigated. Calculated absorbed dose profiles for photons and 4He ions suggest that low-energy beta-gamma and alpha emitting radionuclides can deposit sufficient absorbed dose to disrupt a tumor’s vascular structure while minimizing the dose outside the blood vessel. Candidate radionuclides uniformly distributed in microspheres are theoretically investigated with respect to their vascular disruption potential and to offer an alternative to 90Y microsphere therapy. Requisite activities of candidate low-energy beta-gamma and alpha emitting radionuclides to facilitate vascular disruption are calculated.

  7. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva


    muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  8. Magnetic forces enable controlled drug delivery by disrupting endothelial cell-cell junctions (United States)

    Qiu, Yongzhi; Tong, Sheng; Zhang, Linlin; Sakurai, Yumiko; Myers, David R.; Hong, Lin; Lam, Wilbur A.; Bao, Gang


    The vascular endothelium presents a major transport barrier to drug delivery by only allowing selective extravasation of solutes and small molecules. Therefore, enhancing drug transport across the endothelial barrier has to rely on leaky vessels arising from disease states such as pathological angiogenesis and inflammatory response. Here we show that the permeability of vascular endothelium can be increased using an external magnetic field to temporarily disrupt endothelial adherens junctions through internalized iron oxide nanoparticles, activating the paracellular transport pathway and facilitating the local extravasation of circulating substances. This approach provides a physically controlled drug delivery method harnessing the biology of endothelial adherens junction and opens a new avenue for drug delivery in a broad range of biomedical research and therapeutic applications.

  9. Validation of the development methodologies


    Lahlouhi, Ammar


    This paper argues that modelling the development methodologies can improve the multi-agents systems software engineering. Such modelling allows applying methods, techniques and practices used in the software development to the methodologies themselves. The paper discusses then the advantages of the modelling of development methodologies. It describes a model of development methodologies, uses such a model to develop a system of their partial validation, and applies such a system to multi-agen...

  10. Implementation of a vascular access quality programme improves vascular access care

    NARCIS (Netherlands)

    van Loon, M.; van der Mark, W.; Beukers, N.; de Bruin, C.; Blankestijn, P. J.; Huisman, R. M.; Zijlstra, J. J.; van der Sande, F. M.; Tordoir, J. H. M.

    Introduction. In the Netherlands an access quality improvement plan (QIP) was introduced by vascular access coordinators (VAC) with the aim to decrease vascular access-related complications by preemptive intervention of malfunctioning accesses. A vascular access QIP was established in 24 centres

  11. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    Energy Technology Data Exchange (ETDEWEB)

    Baer, Caroline; Squadrito, Mario Leonardo [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Iruela-Arispe, M. Luisa, E-mail: [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles 90095, CA (United States); De Palma, Michele, E-mail: [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland)


    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches.

  12. Vascularization mediated by mesenchymal stem cells from bone marrow and adipose tissue: a comparison

    Directory of Open Access Journals (Sweden)

    Karoline Pill


    Full Text Available Tissue-engineered constructs are promising to overcome shortage of organ donors and to reconstruct at least parts of injured or diseased tissues or organs. However, oxygen and nutrient supply are limiting factors in many tissues, especially after implantation into the host. Therefore, the development of a vascular system prior to implantation appears crucial. To develop a functional vascular system, different cell types that interact with each other need to be co-cultured to simulate a physiological environment in vitro. This review provides an overview and a comparison of the current knowledge of co-cultures of human endothelial cells (ECs with human adipose tissue-derived stem/stromal cells (ASCs or bone marrow-mesenchymal stem cells (BMSCs in three dimensional (3D hydrogel matrices. Mesenchymal stem cells (MSCs, BMSCs or ASCs, have been shown to enhance vascular tube formation of ECs and to provide a stabilizing function in addition to growth factor delivery and permeability control for ECs. Although phenotypically similar, MSCs from different tissues promote tubulogenesis through distinct mechanisms. In this report, we describe differences and similarities regarding molecular interactions in order to investigate which of these two cell types displays more favorable characteristics to be used in clinical applications. Our comparative study shows that ASCs as well as BMSCs are both promising cell types to induce vascularization with ECs in vitro and consequently are promising candidates to support in vivo vascularization.

  13. Vascular endothelial growth factor blockade alters magnetic resonance imaging biomarkers of vascular function and decreases barrier permeability in a rat model of lung cancer brain metastasis. (United States)

    Pishko, Gregory L; Muldoon, Leslie L; Pagel, Michael A; Schwartz, Daniel L; Neuwelt, Edward A


    Blockade of vascular endothelial growth factor (VEGF) to promote vascular normalization and inhibit angiogenesis has been proposed for the treatment of brain metastases; however, vascular normalization has not been well-characterized in this disease. We investigated the effect of treatment with bevacizumab anti-VEGF antibody on magnetic resonance imaging (MRI) biomarkers of brain tumor vascular characteristics in comparison to small molecule delivery in a rat model of human lung cancer brain metastasis. Athymic rats with A549 human lung adenocarcinoma intracerebral xenografts underwent MRI at 11.75 T before and one day after treatment with bevacizumab (n = 8) or saline control (n = 8) to evaluate tumor volume, free water content (edema), blood volume and vascular permeability (Ktrans). One day later, permeability to 14C-aminoisobutyric acid (AIB) was measured in tumor and brain to assess the penetration of a small drug-like molecule. In saline control animals, tumor volume, edema and permeability increased over the two day assessment period. Compared to controls, bevacizumab treatment slowed the rate of tumor growth (P = 0.003) and blocked the increase in edema (P = 0.033), but did not alter tumor blood volume. Bevacizumab also significantly reduced Ktrans (P = 0.033) and AIB passive permeability in tumor (P = 0.04), but not to peritumoral tissue or normal brain. Post-treatment Ktrans correlated with AIB levels in the bevacizumab-treated rats but not in the saline controls. The correlation of an MRI biomarker for decreased vascular permeability with decreased AIB concentration in tumor after antiangiogenic treatment suggests that bevacizumab partially restored the normal low permeability characteristics of the blood-brain barrier in a model of human lung cancer brain metastasis.

  14. Differences in vascular reactivity between pregnant women with chronic hypertension and preeclampsia. (United States)

    Mori, Toshitaka; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Shinohara, Koichi; Wakatsuki, Akihiko


    The purpose of this study was to evaluate the distinct pathogenic mechanisms underlying chronic hypertension in pregnancy and preeclampsia in terms of oxidative stress and vascular reactivity. A total of 17 women with uncomplicated pregnancies, 30 women with preeclampsia and 17 women with chronic hypertension were evaluated. We measured serum derivatives of reactive oxygen metabolites (d-ROMs; marker of oxygen free radicals), flow-mediated vasodilation (FMD; marker of endothelial function) and intima-media thickness in the carotid artery (IMT; marker of atherogenesis) during pregnancy and 1 month after delivery. Serum d-ROM concentrations were significantly higher in women with chronic hypertension and severe preeclampsia than in the control group during pregnancy. d-ROM concentrations in all groups significantly decreased to similar levels 1 month after delivery. FMD was significantly lower during pregnancy in preeclamptic and chronic hypertension groups compared with the control group. FMD in preeclamptic groups significantly increased and normalized to control levels after delivery. Similarly, FMD in the chronic hypertension group significantly increased after delivery but was still lower. IMT in the chronic hypertension group was significantly higher than that in control and preeclamptic groups. These findings suggest that endothelial dysfunction induced by enhanced oxidative stress is reversible in women with preeclampsia, whereas impaired vascular reactivity may be associated with atherosclerotic changes in women with chronic hypertension.

  15. Cytosolic delivery: Just passing through (United States)

    Sánchez-Navarro, Macarena; Teixidó, Meritxell; Giralt, Ernest


    Intracellular protein delivery has been a major challenge in the field of cell biology for decades. Engineering such delivery is a key step in the development of protein- and antibody-based therapeutics. Now, two different approaches that enable the delivery of antibodies and antibody fragments into the cytosol have been developed.

  16. Drug delivery with living cells

    NARCIS (Netherlands)

    Fliervoet, Lies A L; Mastrobattista, Enrico


    The field of drug delivery has grown tremendously in the past few decades by developing a wide range of advanced drug delivery systems. An interesting category is cell-based drug delivery, which includes encapsulation of drugs inside cells or attached to the surface and subsequent transportation

  17. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

    NARCIS (Netherlands)

    Kanhai, D.A.N.I.S.


    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society,

  18. [Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic]. (United States)

    Liu, Han-Min


    Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

  19. Vascular compliance limits during sleep deprivation and recovery sleep. (United States)

    Phillips, Derrick J; Schei, Jennifer L; Rector, David M


    Our previous studies showed that evoked hemodynamic responses are smaller during wake compared to sleep; suggesting neural activity is associated with vascular expansion and decreased compliance. We explored whether prolonged activity during sleep deprivation may exacerbate vascular expansion and blunt hemodynamic responses. Evoked auditory responses were generated with periodic 65 dB speaker clicks over a 72-h period and measured with cortical electrodes. Evoked hemodynamic responses were measured simultaneously with optical techniques using three light-emitting diodes, and a photodiode. Animals were housed in separate 30×30×80 cm enclosures, tethered to a commutator system and maintained on a 12-h light/dark cycle. Food and water were available ad libitum. Seven adult female Sprague-Dawley rats. Following a 24-h baseline recording, sleep deprivation was initiated for 0 to 10 h by gentle handling, followed by a 24-h recovery sleep recording. Evoked electrical and hemodynamic responses were measured before, during, and after sleep deprivation. Following deprivation, evoked hemodynamic amplitudes were blunted. Steady-state oxyhemoglobin concentration increased during deprivation and remained high during the initial recovery period before returning to baseline levels after approximately 9-h. Sleep deprivation resulted in blood vessel expansion and decreased compliance while lower basal neural activity during recovery sleep may allow blood vessel compliance to recover. Chronic sleep restriction or sleep deprivation could push the vasculature to critical levels, limiting blood delivery, and leading to metabolic deficits with the potential for neural trauma.

  20. Pyomyositis after vaginal delivery.

    LENUS (Irish Health Repository)

    Gaughan, Eve


    Pyomyositis is a purulent infection of skeletal muscle that arises from haematogenous spread, usually with abscess formation. It can develop after a transient bacteraemia of any cause. This type of infection has never been reported before in the literature after vaginal delivery. A 34-year-old woman had progressive severe pain in the left buttock and thigh and weakness in the left lower limb day 1 post spontaneous vaginal delivery. MRI showed severe oedema of the left gluteus, iliacus, piriformis and adductor muscles of the left thigh and a small fluid collection at the left hip joint. She was diagnosed with pyomyositis. She had fever of 37.9°C immediately postpartum and her risk factors for bacteraemia were a mild IV cannula-associated cellulitis and labour itself. She required prolonged treatment with antibiotics before significant clinical improvement was noted.

  1. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh


    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  2. Social video content delivery

    CERN Document Server

    Wang, Zhi; Zhu, Wenwu


    This brief presents new architecture and strategies for distribution of social video content. A primary framework for socially-aware video delivery and a thorough overview of the possible approaches is provided. The book identifies the unique characteristics of socially-aware video access and social content propagation, revealing the design and integration of individual modules that are aimed at enhancing user experience in the social network context. The change in video content generation, propagation, and consumption for online social networks, has significantly challenged the traditional video delivery paradigm. Given the massive amount of user-generated content shared in online social networks, users are now engaged as active participants in the social ecosystem rather than as passive receivers of media content. This revolution is being driven further by the deep penetration of 3G/4G wireless networks and smart mobile devices that are seamlessly integrated with online social networking and media-sharing s...

  3. Vascular applications of contrast-enhanced ultrasound imaging. (United States)

    Mehta, Kunal S; Lee, Jake J; Taha, Ashraf A; Avgerinos, Efthymios; Chaer, Rabih A


    Contrast-enhanced ultrasound (CEUS) imaging is a powerful noninvasive modality offering numerous potential diagnostic and therapeutic applications in vascular medicine. CEUS imaging uses microbubble contrast agents composed of an encapsulating shell surrounding a gaseous core. These microbubbles act as nearly perfect intravascular reflectors of ultrasound energy and may be used to enhance the overall contrast and quality of ultrasound images. The purpose of this narrative review is to survey the current literature regarding CEUS imaging and discuss its diagnostic and therapeutic roles in current vascular and selected nonvascular applications. The PubMed, MEDLINE, and Embase databases were searched until July 2016 using the PubMed and Ovid Web-based search engines. The search terms used included contrast-enhanced, microbubble, ultrasound, carotid, aneurysm, and arterial. The diagnostic and therapeutic utility of CEUS imaging has grown exponentially, particularly in the realms of extracranial carotid arterial disease, aortic disease, and peripheral arterial disease. Studies have demonstrated that CEUS imaging is diagnostically superior to conventional ultrasound imaging in identifying vessel irregularities and measuring neovascularization to assess plaque vulnerability and end-muscle perfusion. Groups have begun to use microbubbles as agents in therapeutic applications for targeted drug and gene therapy delivery as well as for the enhancement of sonothrombolysis. The emerging technology of microbubbles and CEUS imaging holds considerable promise for cardiovascular medicine and cancer therapy given its diagnostic and therapeutic utility. Overall, with proper training and credentialing of technicians, the clinical implications are innumerable as microbubble technology is rapidly bursting onto the scene of cardiovascular medicine. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  4. Microneedles: A New Frontier in Nanomedicine Delivery. (United States)

    Larrañeta, Eneko; McCrudden, Maelíosa T C; Courtenay, Aaron J; Donnelly, Ryan F


    This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN.

  5. Iontophoretic drug delivery across the nail. (United States)

    Delgado-Charro, Maria Begoña


    Topical drug delivery to treat nail diseases such as onychomycosis and psoriasis is receiving increasing attention. Topical nail delivery is challenged by the complicated structure of the nail and the low permeability of most drugs across the nail plate. Considerable effort has been directed at developing methods to promote drug permeation across the nail plate. Iontophoresis efficiently enhances molecular transport across the skin and the eye and is now being tested for its potential in ungual delivery. This review covers the basic mechanisms of transport (electro-osmosis and -migration) and their relative contribution to nail iontophoresis as well as the key factors governing nail permselectivity and ionic transport numbers. Methodological issues concerning research in this area are summarized. The data available in vivo on nail iontophoresis of terbinafine specifically are reviewed in separate sections. Our understanding of nail iontophoresis has improved considerably since 2007; most decisively, the feasibility of nail iontophoresis in vivo has been clearly demonstrated. Future work is required to establish the adequate implementation of the technique so that its clinical efficacy to treat onychomycosis and nail psoriasis can be unequivocally determined.


    Directory of Open Access Journals (Sweden)

    Vladimír Vietoris


    Full Text Available Sensory science is the young but the rapidly developing field of the food industry. Actually, the great emphasis is given to the production of rapid techniques of data collection, the difference between consumers and trained panel is obscured and the role of sensory methodologists is to prepare the ways for evaluation, by which a lay panel (consumers can achieve identical results as a trained panel. Currently, there are several conventional methods of sensory evaluation of food (ISO standards, but more sensory laboratories are developing methodologies that are not strict enough in the selection of evaluators, their mechanism is easily understandable and the results are easily interpretable. This paper deals with mapping of marginal methods used in sensory evaluation of food (new types of profiles, CATA, TDS, napping.

  7. [Impact of premature birth on long term cardio-cerebral vascular events of puerpera]. (United States)

    Li, Dongqing; Tao, Jie; Dong, Yan; Zhao, Haiyan; Gao, Xinying; Ji, Chunpeng; Wang, Lijiao; Xiang, Honghu; Wu, Shouling


    To investigate the impact of premature birth on long term cardio-cerebral vascular events of puerpera. Ambispective cohort study method was used and 3 659 pregnant women giving birth during October 1976 to December 2008 at Kailuan medical group were included and divided into premature birth (PTB) group (n = 226) and non-PTB (NPTB) group (n = 3 433) by the history of PTB. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. (1) The childbearing age, proportion of pregnancy-induced hypertension, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while weight and height of newborn were significantly less in PTB group than in NPTB group (P cardio-cerebral vascular events during the follow-up of (15.19 ± 7.75) years. In PTB group, the incidence of cardio-cerebral vascular events and myocardial infarction was 3.23/1 000 person-years and 2.05/1 000 person-years, respectively, while the corresponding incidence was 1.15/1 000 person-years and 0.42/1 000 person-years, respectively in NPTB group (all P cardio-cerebral vascular events, myocardial infarction in PTB group was 2.03 fold (95% CI: 1.02-4.04, P = 0.002) and 3.11 fold (95% CI: 1.18-8.18, P cardio-cerebral vascular events, especially myocardial infarction of puerpera.

  8. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush M.


    Global delivery models (GDMs) are transforming the global IT and business process outsourcing industry. GDMs are a new form of client-specific investment promoting service integration with clients by combining client proximity with time-zone spread for 24/7 service operations. We investigate....... Findings imply that coordination across time zones increasingly affects international operations in business-to-business and born-global industries....

  9. FPGA controlled artificial vascular system

    Directory of Open Access Journals (Sweden)

    Laqua D.


    Full Text Available Monitoring the oxygen saturation of an unborn child is an invasive procedure, so far. Transabdominal fetal pulse oximetry is a promising method under research, used to estimate the oxygen saturation of a fetus noninvasively. Due to the nature of the method, the fetal information needs to be extracted from a mixed signal. To properly evaluate signal processing algorithms, a phantom modeling fetal and maternal blood circuits and tissue layers is necessary. This paper presents an improved hardware concept for an artificial vascular system, utilizing an FPGA based CompactRIO System from National Instruments. The experimental model to simulate the maternal and fetal blood pressure curve consists of two identical hydraulic circuits. Each of these circuits consists of a pre-pressure system and an artificial vascular system. Pulse curves are generated by proportional valves, separating these two systems. The dilation of the fetal and maternal artificial vessels in tissue substitutes is measured by transmissive and reflective photoplethysmography. The measurement results from the pressure sensors and the transmissive optical sensors are visualized to show the functionality of the pulse generating systems. The trigger frequency for the maternal valve was set to 1 per second, the fetal valve was actuated at 0.7 per second for validation. The reflective curve, capturing pulsations of the fetal and maternal circuit, was obtained with a high power LED (905 nm as light source. The results show that the system generates pulse curves, similar to its physiological equivalent. Further, the acquired reflective optical signal is modulated by the alternating diameter of the tubes of both circuits, allowing for tests of signal processing algorithms.

  10. Vascular permeability alterations induced by arsenic. (United States)

    Chen, Shih-Chieh; Tsai, Ming-Hsien; Wang, Hsiu-Jen; Yu, Hsin-Su; Chang, Louis W


    The impact of arsenic on the integrity of blood vessels in vivo via in situ exposure (local injection) of arsenic was investigated. Vascular permeability changes were evaluated by means of the Evans blue assay and the India ink tracer techniques. Rats were intravenously injected with Evans blue followed by intradermal injections of various doses of sodium arsenite on the back skins of the animals. Evans blue at different time points was extracted and assayed as indices of vascular leakage. Skin at various time point injection sites was sampled for arsenic measurement via graphite furnace atomic absorption spectroscopy. Our time course study with Evans blue technique demonstrated a biphasic pattern of vascular permeability change: an early phase of permeability reduction and a later phase of permeability promotion at all dose levels tested. The India ink tracer technique also demonstrated a time-correlated increase in vascular labelling in the tissues examined, signifying an increase in vascular leakage with time. Moreover, we found that despite an early increase in tissue arsenic content at time of injection, tissue arsenic declined rapidly and returned to near control levels after 30-60 min. Thus, an inverse correlation between tissue arsenic content and the extent of vascular permeability was apparent. This study provides the first demonstration that in situ exposure to arsenic will produce vascular dysfunction (vascular leakage) in vivo.

  11. Functional preservation of vascular smooth muscle tissue (United States)

    Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.


    The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.


    African Journals Online (AJOL)

    Daniel Owu

    Summary: The precise mechanism by which ketamine induces relaxation of vascular smooth muscle is not clear. The goal of this study was to further characterize the vascular actions of ketamine in rabbit aortic smooth muscles. Ring segments (2mm) of rabbit aortae were suspended in 20ml organ baths containing ...

  13. Arteriovenous Malformations and Other Vascular Malformation Syndromes (United States)

    Whitehead, Kevin J.; Smith, Matthew C. P.; Li, Dean Y.


    Vascular malformations are a disruption of the normal vascular pattern in which it is expected that a capillary network of microscopic vessels lies interposed between high-pressure arteries that deliver blood and thin-walled veins that collect low-pressure blood for return to the heart. In the case of arteriovenous malformations, arteries or arterioles connect directly to the venous collection system, bypassing any capillary bed. Clinical consequences result from rupture and hemorrhage, from dramatically increased blood flow, or from the loss of capillary functions such as nutrient exchange and filtering function. These malformations can occur sporadically or as a component of inherited vascular malformation syndromes. In these and other hereditary vascular malformation syndromes, genetic studies have identified proteins and pathways involved in vascular morphogenesis and development. A common theme observed is that vascular malformations result from disruption in pathways involved in vascular stability. Here we review the vascular malformations and pathways involved in hereditary hemorrhagic telangiectasia, capillary malformation–arteriovenous malformation, cerebral cavernous malformations, and mucocutaneous venous malformations. PMID:23125071

  14. Non-suture methods of vascular anastomosis

    NARCIS (Netherlands)

    Zeebregts, CJ; Heijmen, RH; van den Dungen, JJ; van Schilfgaarde, R

    Background: The main aim of performing a vascular anastomosis is to achieve maximal patency rates. An important factor to achieve that goal is to minimize damage to the vessel walls. Sutures inevitably induce vascular wall damage, which influences the healing of the anastomosis. Over time, several

  15. Vascular birthmarks of infancy: resolving nosologic confusion. (United States)

    Hand, Jennifer L; Frieden, Ilona J


    The terminology describing congenital vascular birthmarks has been a source of confusion in the medical literature. Mulliken and Glowacki [1982: Plas. Recons. Surg. 69:412-422] published a biologic classification system which has become the most widely accepted framework for classifying vascular birthmarks and is accepted as the official classification schema by the International Society for the Study of Vascular Anomalies (ISSVA). In this study, we evaluate the current nosology of vascular birthmarks used in standard medical genetics reference texts compared with the accepted Mulliken ISSVA framework. In five sources examined, a variety of terms were used to describe congenital vascular anomalies. The degree of agreement with accepted ISSVA classification varied both within and among texts, with agreement as low as 22% and as high as 75%. In all texts, hemangioma was the most commonly used term, appearing 79 times. Use of the term "hemangioma" had the lowest rate of agreement with the ISSVA classification criteria, with agreement in 23% of citations. The terms "vascular malformation" and "port-wine stain" were used less frequently, but with a much higher degree of agreement with the ISSVA classification: 82% and 66%, respectively. These results establish that nosologic confusion is widespread even in standard genetic reference texts. In particular, the term "hemangioma" is used imprecisely. The ISSVA classification system provides an extremely useful framework for geneticists to classify vascular birthmarks in their evaluation of infants and children with vascular anomalies in order to provide more accurate evaluation, prognosis, and genetic counseling. Copyright 2002 Wiley-Liss, Inc.

  16. Hemorrhage Control for Major Traumatic Vascular Injuries (United States)


    and it is unclear if this contributed to the high (46%) mortality in OPEN patients with thoracic aortic injury. Intra- abdominal arterial hemorrhage...Endovascular therapy for overcoming challenges presented with blunt abdominal aortic injury. Vascular and endovascular surgery 2012;46:329-331. 23...systematically define the clinical and logistical issues surrounding traditional open vascular surgery and catheter-based hemorrhage control. The

  17. Vascular dementia | Connor | African Journal of Psychiatry

    African Journals Online (AJOL)

    Vascular dementia (VaD) is a common but heterogeneous condition in which there is a clear temporal relationship between the dementia and vascular disease. It may result from multiple large or small vessel strokes or a single strategic stroke. Subcortical ischaemic VaD includes multiple lacunes and subcortical ...

  18. Evaluation of Peripheral Vascular Calcification and Serum ...

    African Journals Online (AJOL)

    Introduction: Vascular calcification is a risk factor for cardiovascular mortality in the general population. It is highly prevalent in end stage renal disease (ESRD) patients. Low magnesium (Mg) levels have been reported to have a strong association with vascular calcification in hemodialysis (HD) patients. The aims of this ...

  19. Management Strategies in Hemodialysis Vascular Access

    NARCIS (Netherlands)

    J. van der Linden (Joke)


    textabstractSince the introduction of the AV fistula and the use of interposition graft little improvement has been made in the vascular access field. Still, vascular access related complications, are one of the most important reasons for patient hospitalization, morbidity and even mortality

  20. Reconstructive vascular surgery below the knee

    DEFF Research Database (Denmark)

    Rasmussen, L B; Jelnes, R; Sager, P


    In a series of 38 consecutive patients with advanced peripheral vascular disease (i.e. rest pain) reconstructive vascular surgery was performed with the distal anastomosis below the knee. Ankle/arm pressure index (AAI) was 0.28 (0.11-0.47) preoperatively; accumulated graft patency rate was 0.47 (SD...

  1. Percutaneous Treatment of Peripheral Vascular Malformations

    NARCIS (Netherlands)

    E. van der Linden (Edwin)


    textabstractVascular malformations arise from errors in the morphological processes that shape the embryonic vascular system during fetal development. These developmental errors result in abnormal clusters of blood vessels. Although these lesions are present at birth, they might not become visible

  2. Situating methodology within qualitative research. (United States)

    Kramer-Kile, Marnie L


    Qualitative nurse researchers are required to make deliberate and sometimes complex methodological decisions about their work. Methodology in qualitative research is a comprehensive approach in which theory (ideas) and method (doing) are brought into close alignment. It can be difficult, at times, to understand the concept of methodology. The purpose of this research column is to: (1) define qualitative methodology; (2) illuminate the relationship between epistemology, ontology and methodology; (3) explicate the connection between theory and method in qualitative research design; and 4) highlight relevant examples of methodological decisions made within cardiovascular nursing research. Although there is no "one set way" to do qualitative research, all qualitative researchers should account for the choices they make throughout the research process and articulate their methodological decision-making along the way.

  3. PanVascular medicine. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Lanzer, Peter (ed.) [Health Care Center Bitterfeld (Germany). Division of Cardiovascular Disease


    Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.

  4. Fundamental principles of vascular network topology. (United States)

    Kopylova, Veronika S; Boronovskiy, Stanislav E; Nartsissov, Yaroslav R


    The vascular system is arguably the most important biological system in many organisms. Although the general principles of its architecture are simple, the growth of blood vessels occurs under extreme physical conditions. Optimization is an important aspect of the development of computational models of the vascular branching structures. This review surveys the approaches used to optimize the topology and estimate different geometrical parameters of the vascular system. The review is focused on optimizations using complex cost functions based on the minimum total energy principle and the relationship between the laws of growth and precise vascular network topology. Experimental studies of vascular networks in different species are also discussed. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  5. Stem/Progenitor cells in vascular regeneration. (United States)

    Zhang, Li; Xu, Qingbo


    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  6. Using Polymeric Scaffolds for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Alida Abruzzo


    Full Text Available With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. This review describes the development of polymeric materials over the years and current tissue engineering strategies for the improvement of vascular conduits.

  7. Hedgehog and Resident Vascular Stem Cell Fate

    Directory of Open Access Journals (Sweden)

    Ciaran J. Mooney


    Full Text Available The Hedgehog pathway is a pivotal morphogenic driver during embryonic development and a key regulator of adult stem cell self-renewal. The discovery of resident multipotent vascular stem cells and adventitial progenitors within the vessel wall has transformed our understanding of the origin of medial and neointimal vascular smooth muscle cells (SMCs during vessel repair in response to injury, lesion formation, and overall disease progression. This review highlights the importance of components of the Hh and Notch signalling pathways within the medial and adventitial regions of adult vessels, their recapitulation following vascular injury and disease progression, and their putative role in the maintenance and differentiation of resident vascular stem cells to vascular lineages from discrete niches within the vessel wall.

  8. Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'. (United States)

    Akhtar, Naseem; Khan, Riaz A


    Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Lactogenesis failure following successful delivery of advanced abdominal pregnancy. (United States)

    Pieh-Holder, Kelly L; Scardo, James A; Costello, Deborah H


    Abdominal pregnancy is a rare condition with significant risk of maternal and fetal morbidity and mortality. Because of the vascular involvement, the placenta is often left in situ. Prior reports have neglected to discuss the implications of leaving the placenta in situ on breastfeeding and lactation. We present a case of failure of lactogenesis II following the successful delivery of an advanced abdominal pregnancy in which the placenta was left in situ. This is the first report to discuss the effects on lactation of leaving the placenta in situ as a conservative management option in advanced abdominal pregnancy.

  10. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance

    NARCIS (Netherlands)

    Rol, N.; Timmer, E.M.; Faes, T.J.; Noordegraaf, A.V.; Grunberg, K.; Bogaard, H.J.; Westerhof, N.


    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall

  11. Taking care of your vascular access for hemodialysis (United States)

    ... below as a reminder. What Is a Vascular Access? A vascular access is an opening made in your skin ... access into your body. Know What Type of Vascular Access You Have There are 3 main types of ...

  12. [Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia]. (United States)

    Casas, Meritxell; Calvet, Xavier; Vergara, Mercedes; Bella, Maria Rosa; Junquera, Félix; Martinez-Bauer, Eva; Campo, Rafael


    Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  13. Scientific methodology applied. (United States)

    Lussier, A


    The subject of this symposium is naproxen, a new drug that resulted from an investigation to find a superior anti-inflammatory agent. It was synthesized by Harrison et al. in 1970 at the Syntex Institute of Organic Chemistry and Biological Sciences. How can we chart the evolution of this or any other drug? Three steps are necessary: first, chemical studies (synthesis, analysis); second, animal pharmacology; third, human pharmacology. The last step can additionally be divided into four phases: metabolism and toxicology of the drug in normal volunteers; dose titration and initial clinical trials with sick subjects (pharmacometry); confirmatory clinical trials when the drug is accepted on the market and revaluation (familiarization trials). To discover the truth about naproxen, we must all participate actively with a critical mind, following the principles of scientific methodology. We shall find that the papers to be presented today all deal with the third step in the evaluation process--clinical pharmacology. It is quite evident that the final and most decisive test must be aimed at the most valuable target: the human being. The end product of this day's work for each of us should be the formation of an opinion based on solid scientific proofs. And let us hope that we will all enjoy fulfilling the symposium in its entire etymological meaning this evening. In vino veritas.

  14. Cancer cytogenetics: methodology revisited. (United States)

    Wan, Thomas S K


    The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed.

  15. The use of microbubbles to target drug delivery

    Directory of Open Access Journals (Sweden)

    Porter Richard


    Full Text Available Abstract Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed.

  16. A Framework For Software Quality Assurance Using Agile Methodology

    Directory of Open Access Journals (Sweden)

    Maria Sagheer


    Full Text Available Abstract Agile methodology that uses iterative and incremental approach is widely used in the industry projects as they can satisfy to the change of requirements. Efficient product delivery is achieved by using short iterations. But assuring the quality in any system is essential and imperative part which is very difficult task which raises a question that Is quality is assured in the software which is developed using agile methodology The research paper proposed a solution and summarizes that how the quality is achieved or assure in agile software development using different factors. The major focus of this research paper is to analyse the quality parameter which assure quality in the agile methodology. The research paper includes the brief overview of the parameters which assure quality in agile.

  17. A systematic review of the effect of telephone, internet or combined support for carers of people living with Alzheimer's, vascular or mixed dementia in the community. (United States)

    Jackson, David; Roberts, Gail; Wu, Min Lin; Ford, Rosemary; Doyle, Colleen


    The objective of this review was to assess the effectiveness of interventions delivered by telephone, internet or combined formats to support carers of community dwelling people living with Alzheimer's Disease, vascular dementia or mixed dementia. English language literature published up to 2016 was searched. The initial search included: MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), and PsycINFO. A second search was conducted using Medical Subject Headings (MeSH) and keywords for eight databases. The review included randomised controlled trials, non-randomised controlled trials, quasi-experimental and pre-post studies from published and grey literature. Studies selected for retrieval were assessed by three independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments. Twenty-two studies were included in the review of which 13 were studies of telephone-delivered interventions, five were internet-delivered interventions and four were delivered in a combination of telephone and internet formats. In this review the successful outcomes from the combined telephone and internet delivery exceeded that of telephone alone and internet alone. Very few studies addressed programs for specific types of dementia. When considering the ratio of number of studies to successful outcomes, combined telephone and internet delivery of multicomponent interventions demonstrated relatively more positive outcomes in reducing depression, burden and increasing self-efficacy than telephone alone or internet alone. Further studies are necessary to evaluate the effectiveness of interventions targeted at specific types of dementia and to understand which components of interventions are most effective. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. [A new specialty is born: Vascular medicine]. (United States)

    Laroche, J-P


    On the 4th of December 2015, the French authorities officially recognized the birth of a specialty in vascular medicine entitled CO-DES cardiology-vascular/vascular Medicine. France is the 7th country to obtain this specialty after Switzerland, Germany, Austria, Czech Republic, Slovakia and Slovenia, six countries in the EEC. It has taken years to achieve a long but exciting experience: we went from hopes to disappointments, sometimes with the blues, but lobbying helping… with sustained confidence. This article tells the story of 30 years of struggle to achieve this vascular medicine specialty. Gaston Bachelard wrote: "Nothing is obvious, nothing is given, all is built." For the construction of vascular medicine, we had to overcome many obstacles, nothing was given to us, everything was conquered. Beware "The specialist is one who knows more and more things about an increasingly restricted field, up to 'knowing everything about nothing"' recalled Ralph Barton Ferry, philosopher; so there is room for modesty and humility but also convictions. The physical examination will remain the basis of our exercise. But let us recall the contributions of all those vascular physicians who practiced in the past, together with those currently active, who built day after day, year after year, a vascular medicine of quality. It is because of the trust of our colleagues and our patients that we can occupy the place that is ours today. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Microbleeds in vascular dementia: clinical aspects. (United States)

    Van der Flier, Wiesje M; Cordonnier, Charlotte


    Microbleeds are small dot-like lesions which can be appreciated on gradient echo, T2*-weighted magnetic resonance images as hypointensities. They are considered as an expression of small vessel disease on MRI, next to lacunes and white matter hyperintensities (WMH). Microbleeds are relatively common in vascular dementia, with reported prevalences between 35% and 85%. In the context of vascular dementia, microbleeds are mainly thought to result from hypertensive vasculopathy, but the frequent co-occurrence of lobar microbleeds suggests that neurodegenerative pathology and/or cerebral amyloid angiopathy is also of importance. The presence of multiple microbleeds in vascular dementia or in patients with vascular cognitive impairment is related to worse performance on cognitive tests, mainly in psychomotor speed and executive functioning. They may have some predictive value in terms of predicting development of (vascular) dementia, mortality and disability. Data on the occurrence of stroke and post-stroke dementia in patients with microbleeds are to date not available. New definitions and diagnostic criteria for vascular dementia and vascular cognitive impairment are needed and should take into account microbleeds. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Delivery of enteral nutrition. (United States)

    Grant, M J; Martin, S


    There is increasing evidence that enteral feeding is superior to parenteral nutrition with regard to maintaining gut structure and function. Selection of the enteral access route depends on the type and anticipated duration of nutrient delivery. At present, enteral feeding devices can be divided into two major categories: those entering the gastrointestinal tract through the oral or nasal cavity (oroenteric or nasoenteric tubes) and those entering through the abdominal wall including gastrostomy, duodenostomy, or jejunostomy tubes. This article provides a review of methods to insert and confirm gastric and intestinal feeding tube placement. Care of the patient with an enteric tube will be described.

  1. Vascular-targeted therapies for Duchenne muscular dystrophy (United States)


    Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked recessive, progressive muscle wasting disease caused by the absence of a functional dystrophin protein. Dystrophin has a structural role as a cytoskeletal stabilization protein and protects cells against contraction-induced damage. Dystrophin also serves a signaling role through mechanotransduction of forces and localization of neuronal nitric oxide synthase (nNOS), which produces nitric oxide (NO) to facilitate vasorelaxation. In DMD, the signaling defects produce inadequate tissue perfusion caused by functional ischemia due to a diminished ability to respond to shear stress induced endothelium-dependent dilation. Additionally, the structural defects seen in DMD render myocytes with an increased susceptibility to mechanical stress. The combination of both defects is necessary to generate myocyte damage, which induces successive rounds of myofiber degeneration and regeneration, loss of calcium homeostasis, chronic inflammatory response, fibrosis, and myonecrosis. In individuals with DMD, these processes inevitably cause loss of ambulation shortly after the first decade and an abbreviated life with death in the third or fourth decade due to cardio-respiratory anomalies. There is no known cure for DMD, and although the culpable gene has been identified for more than twenty years, research on treatments has produced few clinically relevant results. Several recent studies on novel DMD therapeutics are vascular targeted and focused on attenuating the inherent functional ischemia. One approach improves vasorelaxation capacity through pharmaceutical inhibition of either phosphodiesterase 5 (PDE5) or angiotensin-converting enzyme (ACE). Another approach increases the density of the underlying vascular network by inducing angiogenesis, and this has been accomplished through either direct delivery of vascular endothelial growth factor (VEGF) or by downregulating the VEGF decoy

  2. MEMS devices for drug delivery. (United States)

    Lee, Hyunjoo J; Choi, Nakwon; Yoon, Eui-Sung; Cho, Il-Joo


    Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Etiological factors of preterm delivery

    Directory of Open Access Journals (Sweden)

    Elvira Brkičević


    Full Text Available Introduction: Preterm delivery is the delivery before 37 weeks of gestation are completed. Preterm birth is a major course of neonatal morbidity and mortality, the incidence of premature delivery in developedcountries is 5 to 9%. Aims of this study were to determine the common etiological factors for preterm delivery, most common weeks of gestation for pretern delivery, and most commom way of delivery for preterm delivery.Methods: The study included 600 patients divided into two groups, experimental group (included 300 preterm delivered pregnant women, control group (included 300 term delivered women.Results: The incidence of preterm delivery in pregnant women younger than 18 years was 4.4%, and in pregnant women older than 35 years was 14%. 44.6 % of preterm delivered women at the experimentalgroup had lower education. In the experimental group burdened obstetrical history had 29%, 17.2% had a preterm delivery, 35.6% had a premature rupture of membranes, 15% had a preterm delivery before32 weeks of gestation, 12.4% between 32-33.6 weeks of gestation, while 72.6% of deliveries were between 34- 36.6 weeks of gestation. Multiple pregnancy as an etiological factor was present in 10.07% ofcases. Extragenital diseases were present in 10.4%. In the experimental group there were 29%, while in the control group there were 15% subjects with burdened obstetrical history.Conclusions: Preterm birth more often occurs in a pregnant women younger than 18 and older than 35 years, and in a pregnant women of lower educational degree. Preterm delivery in the most commoncases was fi nished in period from 34 to 36.6 weeks of gestation. The most common etiological factor of preterm delivery in the experimental group was preterm rupture of membranes and idiopathic pretermdelivery.

  4. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

    CERN Document Server

    Prud'homme, Robert


    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  5. Impact of serological methodology on assessment of the link between Chlamydia pneumoniae and vascular diseases.

    NARCIS (Netherlands)

    Maraha, B.; Heijer, M. den; Kluytmans, J.A.J.W.; Peeters, M.


    We assessed the impact of five serologic tests on the link between Chlamydia pneumoniae and abdominal aortic aneurysms (AAA). The results of the tests were inconsistent. Agreement among the five tests was generally poor. Detection of the link between C. pneumoniae and AAA depends on the serologic

  6. Fascia and Primo Vascular System

    Directory of Open Access Journals (Sweden)

    Chun Yang


    Full Text Available The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS, and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body’s fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

  7. Vascular inflammatory cells in hypertension

    Directory of Open Access Journals (Sweden)

    David G. Harrison


    Full Text Available Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease.

  8. Dental infection and vascular disease. (United States)

    Zoellner, Hans


    Periodontitis is a chronic inflammatory response to bacterial plaque in which the anchoring bone and soft tissues supporting teeth are destroyed, resulting in tooth mobility and loss. Dental caries involves the spread of infection from the dentine to the vascular dental pulp and periapical bony tissues, before involvement of adjacent soft tissues and spreading sepsis. Several case-controlled, cross-sectional, and cohort studies report correlation between periodontitis and increased cardiovascular, cerebrovascular, and peripheral artery disease, as determined by clinical disease, angiography, ultrasonography, and reduced flow-mediated dilation. Some studies report a similar relationship of atherosclerosis with periapical infection and potentially also with coronal caries, and this review identifies the need to investigate these associations further. Smoking and cadmium exposure are epidemiologically confounding environmental risk factors shared by atherosclerosis and periodontitis. Further complicating epidemiological studies are the risk factors for both atherosclerosis and periodontitis, with which periodontitis appears to have separate positive feedback relationships. These include diabetes, increased plasma lipid levels, hypertension, and white blood cell count. Animal and human intervention studies provide some direct support of a causal role for periodontitis in atherosclerosis, and possible mechanisms include bacterial invasion of arteries, specific atherogenic properties of oral bacteria, the acute phase response, and cytokine polymorphisms. © Thieme Medical Publishers.

  9. Intracranial Vascular Malformations and Epilepsy. (United States)

    Josephson, Colin B; Rosenow, Felix; Al-Shahi Salman, Rustam


    Among the spectrum of intracranial vascular malformations (IVMs), arteriovenous malformations (AVMs), and cavernous malformations (CCMs) are of particular importance for epilepsy. Seizures are a common mode of presentation for both conditions. Seizures may occur de novo or secondary to intracerebral hemorrhage. Timely imaging is thus crucial for patients with seizures and AVMs or CCMs. Patients with a first-ever AVM- or CCM-related seizure can now be considered to have epilepsy according to the International League Against Epilepsy criteria. Observational studies and case series suggest that between 45 to 78% of patients with AVM-related epilepsy and 47 to 60% of patients with CCM-related epilepsy may achieve seizure freedom through antiepileptic drugs (AEDs) alone. Invasive procedures are available although current evidence suggests that epilepsy-specific preintervention evaluations are underused. Randomized controlled trials and population-based studies have demonstrated worse short-term functional outcomes after routine intervention on unruptured AVMs or CCMs when compared with conservative management. The role of invasive therapy for IVM-related epilepsy has yielded mixed results. Case series have reported high estimates of seizure freedom although these results have not been replicated in controlled observational studies. Randomized controlled trials of immediate invasive therapy versus conservative management, in addition to usual care with AEDs and of different types of treatment and their timing, are warranted for AVMs and CCM-related epilepsy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)


    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  11. Oral vascular malformations: laser treatment and management (United States)

    Romeo, U.; Rocchetti, F.; Gaimari, G.; Tenore, G.; Palaia, G.; Lo Giudice, G.


    Vascular malformations are a very heterogeneous group of circulatory system's diseases that can involve different kind of vessels: arterial, venous or lymphatic ones. Many treatments, such as conventional surgery, embolization, steroid therapy and laser therapy, are available for vascular lesions. The laser approach relies more therapeutic techniques: the transmucosal thermophotocoagulation, intralesional photocoagulation, the excisional biopsy. Today laser is demonstrated to be the gold standard technique to treat vascular lesions that allows a safe and efficient treatment and a lower post-operative healing time. The only disadvantage is the risk of carbonization that could be avoided by using the multiple-spot single pulsed wave technique.

  12. Imaging evaluation of fetal vascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal [MLC 5031 Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Adams, Denise M. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics and Hemangioma and Vascular Malformation Center, Cincinnati, OH (United States); Gupta, Anita [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Pediatric Surgery and Fetal Center of Cincinnati, Cincinnati, OH (United States)


    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  13. Vascular pathology in the throwing athlete. (United States)

    Dugas, J R; Weiland, A J


    Vascular pathology in the upper extremity of a throwing athlete comprises a spectrum of serious disorders apt to threaten the patient's career and the viability of the involved parts. Such pathology includes digital vessel thrombosis, proximal thrombosis with distal embolization, vessel aneurysm, and vessel compression, such as in thoracic outlet syndrome and quadrilateral space syndrome. This article provides a description of vascular disorders prone to result from sports activities and a review of published data relevant to throwing athletes. Recognition of vascular compromise as a cause for dead arm syndrome or painful digital dysfunction among athletes is essential to prevent the grave consequences of progressive ischemia.

  14. Retroperitoneal vascular malformation mimicking incarcerated inguinal hernia

    Directory of Open Access Journals (Sweden)

    Dubey Indu


    Full Text Available A 30-year-old man presented to the Department of Surgery with a painful groin swelling on right side. Exploration revealed a reddish-blue hemangiomatous mass in the scrotum extending through inguinal canal into the retroperitoneum. On further dissection swelling was found to be originating from right external iliac vein. The swelling was excised after ligating all vascular connections. The histopathological examination of excised mass confirmed the diagnosis of venous variety of vascular malformation. This is the first reported case of vascular malformation arising from retroperitoneum and extending into inguinoscrotal region, presenting as incarcerated inguinal hernia.

  15. Mechanisms of Vascular Aging: New Perspectives (United States)

    Kaley, Gabor; de Cabo, Rafael; Sonntag, William E.; Csiszar, Anna


    This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics. PMID:20576649

  16. Maternal uterine vascular remodeling during pregnancy. (United States)

    Osol, George; Mandala, Maurizio


    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  17. Methodological ignorance : A comment on field experiments and methodological intolerance

    NARCIS (Netherlands)

    Boumans, Marcel|info:eu-repo/dai/nl/075268574


    Glenn Harrison [Journal of Economic Methodology, 2013, 20, 103–117] discusses four related forms of methodological intolerance with respect to field experiments: field experiments should rely on some form of randomization, should be disconnected from theory, the concept of causality should only be

  18. Kaupapa Maori Methodology: Trusting the Methodology through Thick and Thin (United States)

    Hiha, Anne Aroha


    Kaupapa Maori is thoroughly theorised in academia in Aotearoa and those wishing to use it as their research methodology can find support through the writing of a number of Maori academics. What is not so well articulated, is the experiential voice of those who have used Kaupapa Maori as research methodology. My identity as a Maori woman…

  19. Vascular Complications During Catheter Ablation of Cardiac Arrhythmias: A Comparison Between Vascular Ultrasound Guided Access and Conventional Vascular Access. (United States)

    Sharma, Parikshit S; Padala, Santosh K; Gunda, Sampath; Koneru, Jayanthi N; Ellenbogen, Kenneth A


    Vascular access related complications are the most common complications from catheter based EP procedures and have been reported to occur in 1-13% of cases. We prospectively assessed vascular complications in a large series of consecutive patients undergoing catheter based electrophysiologic (EP) procedures with ultrasound (US) guided vascular access versus conventional access. Consecutive patients undergoing catheter ablation procedures at VCU medical center were included. US guided access was obtained in all cases starting June 2015 (US group) while modified Seldinger technique without US guidance (non-US group) was used in cases prior to this date. All vascular complications were recorded for a 30-day period after the procedure. A total of 689 patients underwent 720 procedures. Ablations for ventricular tachyarrhythmias (ventricular tachycardia: VT, premature ventricular contractions: PVCs) accounted for 89 (12%) cases; atrial fibrillation (AF) ablations accounted for 328 procedures (46%) and other catheter based procedures accounted for 42% of cases. A significantly higher incidence of complications was noted in the non-US group compared with the US group (19 [5.3%] vs. 4 [1.1%], respectively, P = 0.002). Major complications were also higher among the non-US group (9 [2.5%] vs. 2 [0.6%], P = 0.03). Increasing age (P = 0.04) and non-US guided vascular access (P = 0.002) were associated with a higher risk of vascular access complications. In a large series of patients undergoing catheter based EP procedures for cardiac arrhythmias, US guided vascular access was associated with a significantly decreased 30-day risk of vascular complications. © 2016 Wiley Periodicals, Inc.

  20. Effect of vascular burden as measured by vascular indexes upon vascular dementia: a matched case-control study

    Directory of Open Access Journals (Sweden)

    Takahashi PY


    Full Text Available Paul Y Takahashi, Casey R Caldwell, Paul V TargonskiPrimary Care Internal Medicine, Mayo Clinic, Rochester MN, USABackground: Vascular dementia (VaD is a challenging illness that affects the lives of older adults and caregivers. It is unclear how multiple vascular risk factor exposures (polyvascular disease affect VaD.Purpose: To determine the relationship between multiple vascular risk exposures, as counted on an index in cases with VaD, compared with healthy age-/gender-matched controls.Methods: This was a matched case-control study of subjects living in Olmsted County, MN with documented VaD. Controls were selected by gender and age within 3 years from those who did not have dementia. The exposures included a total index (eleven exposure factors added together, along with indexes for cerebrovascular disease (two exposures, cardiovascular disease (four exposures, vascular disease (three exposures, and lifestyle (two exposures. Analysis used matched conditional univariable logistic regression for each index.Results: A total of 1736 potential subjects were identified, and 205 subjects were diagnosed with VaD. There was a significant association of the total score index with an odds ratio of 1.45 (95% confidence interval 1.21–1.74. The cerebrovascular index was also associated with VaD with an odds ratio of 12.18 (95% confidence interval 6.29–23.61. The cardiovascular and vascular indexes were also associated with VaD status. The lifestyle index was not associated with VaD.Conclusion: The cumulative role of multiple vascular risk factors or diseases increased the risk of VaD, as noted by the total vascular index. The lifestyle index did not reveal any significant differences. Further work is required for evaluation of these indexes.Keywords: polyvascular disease, elderly, vascular dementia

  1. Incorporation of photo-carbon monoxide releasing materials into electrospun scaffolds for vascular tissue engineering. (United States)

    Michael, Eden; Abeyrathna, Nawodi; Patel, Aatish V; Liao, Yi; Bashur, Chris A


    Hyper-proliferation of smooth muscle cells (SMCs) and a reduction in endothelial cell function are reasons for poor patency rates of current tissue engineered small-diameter vascular grafts. The controlled delivery of carbon monoxide (CO), a gasotransmitter involved in cell signaling, could improve vascular cell function in these grafts. Current CO releasing molecules (CORMs) can improve endothelialization of injured vessels with appropriate doses, but they still have limitations. The goal of this project was to generate a novel tissue engineered scaffold that includes a non-toxic and photoactivatable CORM. This is the first use of a CORM for tissue engineering. The results demonstrated that CORM-loaded, electrospun poly(ɛ-caprolactone) scaffolds can be photo-activated and release CO. The fluorescence that develops after CO release can be used to non-destructively track the extent of reaction. Further, activation can occur when both dry and incubated in cell culture conditions. However, incubation in serum protein-containing media decreases the time frame for activation, demonstrating the importance of testing the release profile in culture conditions. Rat SMCs were able to attach, grow, and express contractile SMC markers on activated CORM-loaded meshes and controls. Overall, these findings demonstrate that CORM-loaded electrospun scaffolds provide a promising delivery system for vascular tissue engineering.

  2. Intradermal Insulin Delivery (United States)

    Hultström, Michael; Roxhed, Niclas


    The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines. PMID:24876605

  3. Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers (United States)

    Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng


    With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

  4. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Timraz, Sara B.H., E-mail: [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Farhat, Ilyas A.H., E-mail: [Department of Applied Mathematics and Sciences, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Alhussein, Ghada, E-mail: [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Christoforou, Nicolas, E-mail: [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Department of Biomedical Engineering, Duke University, Durham, NC 27708 (United States); Teo, Jeremy C.M., E-mail: [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates)


    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  5. Submicron Lipid Emulsions: A Versatile Platform for Drug Delivery. (United States)

    Zhang, Xingwang; Wu, Baojian


    Lipid emulsions have turned out to be a versatile tool for systemic delivery of poorly soluble drugs and cytotoxic drugs. Currently, the majority of marketed or developing drugs are recognized as BCS II and IV ones. How to solve the solubility and systemic administration that enables them access to clinical application is arising a great challenge in drug delivery systems. The key considerations for lipid emulsions are how to enhance the drug load, stability and reproducibility. Formulation and manufacture technique play the leading role in development of lipid emulsions. Understanding the biofate and characterization in vitro/vivo is suggestive to exploit the potential of lipid emulsions. This review discussed the manufacture techniques and in vivo behavior of lipid emulsions. Momentous interests were focused on their applications in drug delivery as well as the future evolution. Finally, we appreciated the methodologies of quality control and systemic risks associated with lipid emulsions.

  6. Mosaic vectors comprised of modified AAV1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells. (United States)

    Stachler, M D; Bartlett, J S


    Vascular-targeted gene therapies have the potential to treat many of the leading causes of mortality in the western world. Unfortunately, these therapies have been ineffective due to poor vascular gene transfer. The use of alternative virus serotypes and the incorporation of vascular targeting ligands into vectors has resulted in only modest increases in vascular gene transfer. Adeno-associated virus (AAV) 1 has shown the most promise among the AAV vectors for the transduction of vascular endothelial cells. However, no straightforward small-scale purification strategy exists for AAV1 as it does for AAV2 making it difficult to quickly produce AAV1 vector for analysis. Here we have combined two AAV1 capsid protein modifications to enhance vascular gene transfer and allow easy purification of vector particles. Mosaic vector particles have been produced comprised of capsid proteins containing the well-characterized RGD4C modification to target integrins present on the vasculature, and capsid proteins containing a modification that permits metabolic biotinylation and efficient purification of mosaic particles by avidin affinity chromatography. We show that the RGD modification results in a 50-100-fold enhancement in endothelial cell gene transfer that is maintained in biotinylated mosaic AAV1 particles. These results suggest that mosaic virions hold significant promise for targeted gene delivery to the vasculature.

  7. Application of Porter’s Five Forces Model and generic strategies for vascular surgery: should be stuck in the middle? (United States)

    Sumpio, Bauer E


    There are many stakeholders in the vascular marketplace from clinicians to hospitals, third party payers, medical device manufacturers and the government. Economic stress, threats of policy reform and changing health-care delivery are adding to the challenges faced by vascular surgeons. Use of Porter's Five Forces analysis to identify the sources of competition, the strength and likelihood of that competition existing, and barriers to competition that affect vascular surgery will help our specialty understand both the strength of our current competition and the strength of a position that our specialty will need to move to. By understanding the nature of the Porter's Five Forces as it applies to vascular surgery, and by appreciating their relative importance, our society would be in a stronger position to defend itself against threats and perhaps influence the forces with a long-term strategy. Porter's generic strategies attempt to create effective links for business with customers and suppliers and create barriers to new entrants and substitute products. It brings an initial perspective that is convenient to adapt to vascular surgery in order to reveal opportunities.Vascular surgery is uniquely situated to pursue both a differentiation and high value leadership strategy.

  8. The importance of nanoparticle shape in cancer drug delivery. (United States)

    Truong, Nghia P; Whittaker, Michael R; Mak, Catherine W; Davis, Thomas P


    Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a

  9. Presymptomatic genetic analysis during pregnancy for vascular type Ehlers–Danlos syndrome

    Directory of Open Access Journals (Sweden)

    Naing BT


    at 8 weeks of pregnancy to minimize the risk of developing vascular EDS-related complications. The negative presymptomatic diagnostic result allowed the patient to choose normal delivery at term. Vascular EDS is a serious disorder, with high mortality, especially in high-risk women with vascular EDS during pregnancy. The presymptomatic genetic testing of vascular EDS during pregnancy for a high-risk family can help with the early establishment of preventive measures.Keywords: vascular EDS, type III procollagen gene (COL3A1, testing

  10. Development of Shakemap Methodologies (United States)

    Erdik, M.; Cagnan, Z.; Zülfikar, C.; Durukal, E.; Sesetyan, K.; Demircioglu, M. B.; Kariptas, C.


    For almost-real time estimation of the ground shaking after a major earthquake in the Euro-Mediterranean region the JRA-3 component of the EU Project entitled "Network of research Infrastructures for European Seismology, NERIES" foresees: 1. Finding of the most likely location of the source of the earthquake using regional seismotectonic data base, supported, if and when possible, by the estimation of fault rupture parameters from rapid inversion of data from on-line regional broadband stations. 2. Estimation of the spatial distribution of selected ground motion parameters at engineering bedrock through region specific ground motion attenuation relationships and/or actual physical simulation of ground motion. 3. Estimation of the spatial distribution of site-specific ground selected motion parameters using regional geology (or urban geotechnical information) data-base using appropriate amplification models. 4. Correlation/verifyication/enrichment of the estimated ground shaking information with the available on-line strong motion data. These shakemaps maps will enable the first estimates of damage and casulaties, and consequently provide vital information within minutes after an earthquake to European emergency response agencies. There are regional dependencies and multiple sources of uncertainty in such estimations stemming from empirical ground motion predictions, non-existent or sparse ground motion measurements, considerations involving fault finiteness and directivity, data interpolations and site modifications. The methodology used by USGS is not directly transportable, due to a region specific characteristics of the empirical attenuation relationships and methods of modification of ground motion for the near-surface geology. Together with researchers from Imperial College, NORSAR and ETH-Zurich, we are developing and testing algorithms for the preparation of shakemaps and the quantification of associated uncertainties. In this connection we have estimated

  11. Hydrogels for Engineering of Perfusable Vascular Networks (United States)

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.


    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

  12. Headache as Risk Factor for Vascular Disease


    J Gordon Millichap


    The association of severe or recurrent headache or migraine with vascular disease in childhood or adolescence was examined by a National Health and Nutrition Survey at the National Institute of Neurological Disease and Stroke and of Mental Health, Bethesda, MD.

  13. Regulation of Vascular Function on Posttranscriptional Level

    Directory of Open Access Journals (Sweden)

    Andreas Eisenreich


    Full Text Available Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (pathophysiologic conditions. Alternative splicing as well as micro (miRNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF or the endothelial nitric oxide synthase (eNOS. This review will summarize and discuss the latest findings on the (pathophysiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone.

  14. Vascular tumors of bone : Imaging findings

    NARCIS (Netherlands)

    Vermaat, Marieke; Vanel, Daniel; Kroon, Herman M.; Verbeke, Sofie L. J.; Alberghini, Marco; Bovee, Judith V. M. G.; Bloem, Johan L.

    Purpose: To identify radiological features of malignant vascular tumors of bone, which can be used to avoid erroneously diagnosing metastases based on radiological multifocality, and histological epitheloid phenotype. Materials and methods: From the databases of the Bologna & Netherlands Committee

  15. Vascular adaption to physical inactivity in humans

    NARCIS (Netherlands)

    Bleeker, M.W.P.


    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  16. Diagnosis and Management of Lymphatic Vascular Disease

    National Research Council Canada - National Science Library

    Rockson, Stanley G


    ... it. The most readily recognizable attribute of lymphatic vascular incompetence is the presence of the characteristic swelling of tissues, called lymphedema, which arises as a consequence of insufficient lymph transport...

  17. Extracellular Matrix Molecules Facilitating Vascular Biointegration

    Directory of Open Access Journals (Sweden)

    Martin K.C. Ng


    Full Text Available All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials.

  18. Evidence for a vascular factor in migraine

    DEFF Research Database (Denmark)

    Asghar, Mohammad S; Hansen, Adam E; Amin, Faisal Mohammad


    It has been suggested that migraine is caused by neural dysfunction without involvement of vasodilatation. Because dismissal of vascular mechanisms seemed premature, we examined diameter of extra- and intracranial vessels in migraine without aura patients....

  19. Hydrogels for Engineering of Perfusable Vascular Networks

    Directory of Open Access Journals (Sweden)

    Juan Liu


    Full Text Available Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

  20. World Federation of Vascular Societies: presidential address

    DEFF Research Database (Denmark)

    Sillesen, Henrik Hegaard


    The presidential address describes briefly the history of the World Federation for Vascular Societies (WFVS) and its objectives. Vascular Surgery today includes interventional procedures (open surgical and endovascular) in addition to risk factor reduction and medical treatment. It is equally imp...... throughout the world. In addition, for introduction of new treatments, training issues and dissemination of science a global organisation like the WFVS is needed.......The presidential address describes briefly the history of the World Federation for Vascular Societies (WFVS) and its objectives. Vascular Surgery today includes interventional procedures (open surgical and endovascular) in addition to risk factor reduction and medical treatment. It is equally....... Similar, in order to be able to train with relevant case mix and numbers, and in order always to have both complex open and endovascular skills on call 24 hours per day, 365 days a year, centralisation into larger units is necessary. The WFVS is important simply looking at the huge demographic differences...

  1. Document delivery services contrasting views

    CERN Document Server


    Design and maintain document delivery services that are ideal for academic patrons! In Document Delivery Services: Contrasting Views, you'll visit four university library systems to discover the considerations and challenges each library faced in bringing document delivery to its clientele. This book examines the questions about document delivery that are most pressing in the profession of library science. Despite their own unique experiences, you'll find common practices among all four?including planning, implementation of service, and evaluation of either user satisfaction and/or vendor per

  2. Delivery methods for LVSD systems (United States)

    Kasner, James H.; Brower, Bernard V.


    In this paper we present formats and delivery methods of Large Volume Streaming Data (LVSD) systems. LVSD systems collect TBs of data per mission with aggregate camera sizes in the 100 Mpixel to several Gpixel range at temporal rates of 2 - 60 Hz. We present options and recommendations for the different stages of LVSD data collection and delivery, to include the raw (multi-camera) data, delivery of processed (stabilized mosaic) data, and delivery of user-defined region of interest windows. Many LVSD systems use JPEG 2000 for the compression of raw and processed data. We explore the use of the JPEG 2000 Interactive Protocol (JPIP) for interactive client/server delivery to thick-clients (desktops and laptops) and MPEG-2 and H.264 to handheld thin-clients (tablets, cell phones). We also explore the use of 3D JPEG 2000 compression, defined in ISO 15444-2, for storage and delivery as well. The delivery of raw, processed, and region of interest data requires different metadata delivery techniques and metadata content. Beyond the format and delivery of data and metadata we discuss the requirements for a client/server protocol that provides data discovery and retrieval. Finally, we look into the future as LVSD systems perform automated processing to produce "information" from the original data. This information may include tracks of moving targets, changes of the background, snap shots of targets, fusion of multiple sensors, and information about "events" that have happened.

  3. Towards a GIS Evaluation Methodology

    African Journals Online (AJOL)


    information systems within public sector organisations. 3. Methodology. This study utilises the case study research methodology detailed in (Yin 1988; Yin 2003; Kumar. 2000) to ... Directorate of Water Resources Management ..... the use of GIS and map data shifts to supporting some decision making in organisations.

  4. A methodology for social experimentation

    DEFF Research Database (Denmark)

    Ravn, Ib

    A methodology is outlined whereby one may improve the performance of a social system to the satisfaction of its stakeholders, that is, facilitate desirable social and organizational transformations......A methodology is outlined whereby one may improve the performance of a social system to the satisfaction of its stakeholders, that is, facilitate desirable social and organizational transformations...

  5. Workshops as a Research Methodology (United States)

    Ørngreen, Rikke; Levinsen, Karin


    This paper contributes to knowledge on workshops as a research methodology, and specifically on how such workshops pertain to e-learning. A literature review illustrated that workshops are discussed according to three different perspectives: workshops as a means, workshops as practice, and workshops as a research methodology. Focusing primarily on…

  6. Choosing a Methodology: Philosophical Underpinning (United States)

    Jackson, Elizabeth


    As a university lecturer, I find that a frequent question raised by Masters students concerns the methodology chosen for research and the rationale required in dissertations. This paper unpicks some of the philosophical coherence that can inform choices to be made regarding methodology and a well-thought out rationale that can add to the rigour of…

  7. Biomimicry, vascular restenosis and coronary stents. (United States)

    Schwartz, R S; van der Giessen, W J; Holmes, D R


    Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

  8. Standardized Definitions for Hemodialysis Vascular Access


    Lee, Timmy; Mokrzycki, Michele; Moist, Louise; Maya, Ivan; Vazquez, Miguel; Lok, Charmaine


    Vascular access dysfunction is one of the leading causes of morbidity and mortality among end-stage renal disease patients 1,2. Vascular access dysfunction exists in all 3 types of available accesses: arteriovenous fistulas, arteriovenous grafts, and tunneled catheters. In order to improve clinical research and outcomes in hemodialysis access dysfunction, the development of a multidisciplinary network of collaborative investigators with various areas of expertise, and common standards for ter...

  9. Vascular Plaque Determination for Stroke Risk Assessment (United States)


    AWARD NUMBER: W81XWH-16-1-0608 TITLE: Vascular Plaque Determination for Stroke Risk Assessment PRINCIPAL INVESTIGATOR: Vince, David Geoffrey...TITLE AND SUBTITLE Vascular Plaque Determination for Stroke Risk Assessment 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0608 5c. PROGRAM... plaques at high risk for initiating a cerebrovascular accident. The core of the current research project is a pilot clinical study to enroll 100 subjects

  10. 3D Bioprinting for Vascularized Tissue Fabrication. (United States)

    Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying


    3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication.

  11. Materials for engineering vascularized adipose tissue. (United States)

    Chiu, Yu-Chieh; Cheng, Ming-Huei; Uriel, Shiri; Brey, Eric M


    Loss of adipose tissue can occur due to congenital and acquired lipoatrophies, trauma, tumor resection, and chronic disease. Clinically, it is difficult to regenerate or reconstruct adipose tissue. The extensive microvsacular network present in adipose, and the sensitivity of adipocytes to hypoxia, hinder the success of typical tissue transfer procedures. Materials that promote the formation of vascularized adipose tissue may offer alternatives to current clinical treatment options. A number of synthetic and natural biomaterials common in tissue engineering have been investigated as scaffolds for adipose regeneration. While these materials have shown some promise they do not account for the unique extracellular microenvironment of adipose. Adipose derived hydrogels more closely approximate the physical and chemical microenvironment of adipose tissue, promote preadipocyte differentiation and vessel assembly in vitro, and stimulate vascularized adipose formation in vivo. The combination of these materials with techniques that promote rapid and stable vascularization could lead to new techniques for engineering stable, vascularized adipose tissue for clinical application. In this review we discuss materials used for adipose tissue engineering and strategies for vascularization of these scaffolds. Materials that promote formation of vascularized adipose tissue have the potential to serve as alternatives or supplements to existing treatment options, for adipose defects or deficiencies resulting from chronic disease, lipoatrophies, trauma, and tumor resection. Copyright © 2009 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  12. [Management of vascular anomalies in children]. (United States)

    Elajmi, A; Clapuyt, P; Hammer, F; Bataille, A-C; Lengele, B; Boon, L M


    Vascular anomalies, which are broadly identified as "angiomas", are rare entities and often unknown by the medical sphere. They are divided in two different categories which carry different prognosis and management: "vascular tumors" and "vascular malformations". Their precise identification is crucial and involves a good knowledge of the biological classification published by Mulliken and Glowacki and that has recently been updated by the International Society for the Study of Vascular Anomalies (ISSVA). Vascular tumors are benign, common, inborn or not and most of the time disappear with growth. Vascular malformations are always congenital and growth with the child. They can involve type of vessels solely or combined with others. A rheologic differentiation between slow and fast flow malformations is essential in order to characterize the seriousness of the lesion. Frequently, their diagnosis is clinically established and the anamnesis is conducted to answer three questions that are the time of revelation of the lesion ("When?"), its aspect ("What?") and its evolution ("How?"). Further investigations are usually not required but a non-invasive imaging technique such as Doppler ultrasound could be useful if a doubt exists. Surgery is not mandatory and must always be well thought because its consequences might be disastrous. It must be left to cosmetic sequelae of these lesions or to lesions that are totally resectable without causing any unacceptable deformation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Cardiopulmonary Manifestations of Collagen Vascular Diseases. (United States)

    Jawad, Hamza; McWilliams, Sebastian R; Bhalla, Sanjeev


    The study aimed to illustrate the cardiopulmonary findings of the following collagen vascular diseases on cross-sectional imaging: rheumatoid arthritis, scleroderma (progressive systemic sclerosis), systemic lupus erythematosus, the inflammatory myopathies (polymyositis/dermatomyositis), and Sjögren's syndrome. Although collagen vascular diseases can affect any part of the body, interstitial lung disease and pulmonary hypertension are the two most important cardiopulmonary complications and are responsible for the majority of morbidity and mortality in this patient population. Interstitial pneumonia with autoimmune features (IPAF) is a newly described entity that encompasses interstitial lung disease in patients with clinical, serologic, or morphologic features suggestive of but not diagnostic of collagen vascular disease; these patients are thought to have better outcomes than idiopathic interstitial pneumonias. Interstitial lung disease and pulmonary hypertension determine the prognosis in collagen vascular disease patients. IPAF is a new term to label patients with possible collagen vascular disease-related interstitial lung disease. Collagen vascular disease patients are at increased risk for various malignancies.

  14. Vascular retraction driven by matrix softening (United States)

    Valentine, Megan

    We recently discovered we can directly apply physical forces and monitor the downstream responses in a living organism in real time through manipulation of the blood vessels of a marine organism called, Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in regulating vascular growth and homeostasis in Botryllus,a basal chordate which has a large, transparent extracorporeal vascular network that can encompass areas >100 cm2. We have determined that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1 activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), caused a rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within 16 hrs. In this talk, I will discuss the molecular and cellular origins of this systemic remodeling event, which hinges upon the ability of the vascular cells to sense and respond to mechanical signals, while introducing this exciting new model system for studies of biological physics and mechanobiology. Collaborators: Anthony DeTomaso, Delany Rodriguez, Aimal Khankhel (UCSB).

  15. Stroke injury, cognitive impairment and vascular dementia☆ (United States)

    Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi


    The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

  16. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  17. Introduction to Investigation And Utilizing Lean Test Metrics In Agile Software Testing Methodologies


    Padmaraj Nidagundi


    The growth of the software development industry approaches the new development methodologies to deliver the error free software to its end-user fulfilling the business values to product. The growth of tools and technology has brought the automation in the development and software testing process, it has also increased the demand of the fast testing and delivery of the software to end customers. Traditional software development methodologies to trending agile software development t...

  18. Buccal delivery of metformin

    DEFF Research Database (Denmark)

    Sander, Camilla; Nielsen, Hanne Mørck; Jacobsen, Jette


    The oral cavity is considered an attractive site of drug administration. Metformin is currently, used in oral diabetes treatment. The aim of the current study was to study the feasibility of metformin, to permeate the buccal epithelium applying a bioadhesive and permeation enhancing drug delivery...... system. The in vitro TR146 cell culture model was used to study the effect of drug concentration (5-100mM) and the impact of a bioadhesive chitosan formulation (discs) and chitosan in solution (0-20mg/mL) acting as a permeation enhancer. The permeation of metformin occurred by passive diffusion via......, suggest that in vivo absorption of therapeutic doses of metformin needs to take place as a combination of buccal and intestinal absorption as metformin therapy requires the use of high doses....

  19. Rhythmomimetic drug delivery

    CERN Document Server

    Calderer, M Carme; Siegel, Ronald A; Yao, Lingxing


    We present modeling, analysis and numerical simulation of a prototype glucose driven drug delivery device based on chemomechanical interactions and volume phase transitions in polyelectrolyte gels. The device consists of two fluid compartments, an external cell (I) mimicking the physiological environment, and a closed chamber (II), separated by a hydrogel membrane. Cell I, which is held at constant pH and ionic strength, provides a constant supply of glucose to cell II, and also serves as clearance station for reaction products. Cell II contains the drug to be delivered to the body, an enzyme that catalyzes conversion of glucose into hydrogen ions, and a piece of marble to remove excess hydrogen ions that would otherwise overwhelm the system. When the membrane is swollen, glucose flux into Cell II is high, leading to rapid production of hydrogen ions. However, the hydrogen ions are not immediately released to Cell I but react, instead, with the negatively charged carboxyl groups of the membrane, which collaps...

  20. Heparin-conjugated polyethylenimine for gene delivery. (United States)

    Jeon, Oju; Yang, Hee Seok; Lee, Tae-Jin; Kim, Byung-Soo


    A major problem when using cationic polymers for gene delivery is that transfection is strongly inhibited by the presence of serum. This shortcoming limits the application of cationic polymers for systematic gene delivery in vivo. Due to the shielding effect of heparin, heparin conjugation to cationic polymers may improve the in vivo gene transfection efficiency. In this study, the transfection efficiency of heparin-conjugated polyethylenimine (HCPEI) with a low molecular weight of 1800 Da was compared to the transfection efficiencies of polyethylenimine with a low molecular weight of 1800 Da (PEI1800), polyethylenimine with a high molecular weight of 25,000 Da (PEI25k), and Lipofectamine. The size of the HCPEI/plasmid DNA (pDNA) complex is approximately 250 nm. HCPEI has a proton-buffering effect and HCPEI/pDNA has higher blood compatibility and a lower cytotoxicity than PEI25k/pDNA and Lipofectamine/pDNA. For in vitro transfection of rabbit smooth muscle cells in serum-free medium, the transfection efficiency of HCPEI/pDNA was not significantly different from those of PEI25k/pDNA and Lipofectamine/pDNA. Importantly, in serum-containing medium, the transfection efficiency of HCPEI/pDNA was significantly higher than those of PEI25k/pDNA and Lipofectamine/pDNA. For vascular endothelial growth factor (VEGF) gene transfection to mouse ischemic limbs, HCPEI/pDNA exhibited significantly higher VEGF expression and more extensive neovascularization than PEI/pDNA and Lipofectamine/pDNA. Taken together, heparin conjugation to PEI improves the in vivo gene transfection efficiency of PEI.

  1. On-chip power delivery and management

    CERN Document Server

    Vaisband, Inna P; Popovich, Mikhail; Mezhiba, Andrey V; Köse, Selçuk; Friedman, Eby G


    This book describes methods for distributing power in high speed, high complexity integrated circuits with power levels exceeding many tens of watts and power supplies below a volt. It provides a broad and cohesive treatment of power delivery and management systems and related design problems, including both circuit network models and design techniques for on-chip decoupling capacitors, providing insight and intuition into the behavior and design of on-chip power distribution systems. Organized into subareas to provide a more intuitive flow to the reader, this fourth edition adds more than a hundred pages of new content, including inductance models for interdigitated structures, design strategies for multi-layer power grids, advanced methods for efficient power grid design and analysis, and methodologies for simultaneously placing on-chip multiple power supplies and decoupling capacitors. The emphasis of this additional material is on managing the complexity of on-chip power distribution networks.

  2. Hypertensive organ damage in patients with vascular disease

    NARCIS (Netherlands)

    Vlek, A.L.M.


    Hypertension is one of the most common vascular risk factors, and is an important cause of development of different vascular diseases. The main aim of this thesis was to determine the burden of hypertension-associated vascular diseases and end-organ damage in patients with manifest vascular disease.

  3. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an

  4. Vascular associated gene variants in patients with preeclampsia

    DEFF Research Database (Denmark)

    Lykke, Jacob A; Bare, Lance A; Olsen, Jørn


    Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms.......Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms....

  5. Maximal muscular vascular conductances during whole body upright exercise in humans

    DEFF Research Database (Denmark)

    Calbet, J A L; Jensen-Urstad, M; Van Hall, Gerrit


    That muscular blood flow may reach 2.5 l kg(-1) min(-1) in the quadriceps muscle has led to the suggestion that muscular vascular conductance must be restrained during whole body exercise to avoid hypotension. The main aim of this study was to determine the maximal arm and leg muscle vascular...... conductances (VC) during leg and arm exercise, to find out if the maximal muscular vasodilatory response is restrained during maximal combined arm and leg exercise. Six Swedish elite cross-country skiers, age (mean +/-s.e.m.) 24 +/- 2 years, height 180 +/- 2 cm, weight 74 +/- 2 kg, and maximal oxygen uptake...... 87 mmHg), systemic VC, systemic oxygen delivery and pulmonary VO2(approximately 4 l min(-1)) attained similar values regardless of exercise mode. The distribution of cardiac output was modified depending on the musculature engaged in the exercise. There was a close relationship between VC and VO2...

  6. Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index. (United States)

    Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R


    Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

  7. The Development of Virtual Education: A Global Perspective. A Study of Current Trends in the Virtual Delivery of Education. (United States)

    Farrell, Glen M., Ed.

    This document contains 11 papers examining the methodology and findings of a study of the virtual delivery of education throughout the world. "Introduction" (Glen M. Farrell) explains the study methodology, which entailed the identification of 10 global regions and commissioning of an individual in each region to write a paper describing the state…

  8. Cartilage oligomeric matrix protein prevents vascular aging and vascular smooth muscle cells senescence. (United States)

    Wang, Meili; Fu, Yi; Gao, Cheng; Jia, Yiting; Huang, Yaqian; Liu, Limei; Wang, Xian; Wang, Wengong; Kong, Wei


    Aging-related vascular dysfunction contributes to cardiovascular morbidity and mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular matrix protein, has been described as a negative regulatory factor for the vascular aging-related processes including atherosclerosis and vascular calcification. However, whether COMP is implicated in the process of vascular aging remains unclear. Here, we identified a novel function of COMP in preventing vascular aging and vascular smooth muscle cells (VSMCs) senescence. Firstly, vascular COMP expression was decreased in three different senescence-accelerated mouse models and was also declining with age. COMP(-/-) mice displayed elevated senescence-associated markers expression, including p53, p21 and p16, in the aortas compared with their wild type (WT) littermates. In accordance, COMP deficiency induced aging-related vascular dysfunction as evidenced by the significantly reduced phenylephrine-induced contraction and increased vascular stiffness as evaluated by pulse wave velocity. The aortic wall of COMP(-/-) mice was susceptible to senescence by displaying senescence-associated β-galactosidase (SA β-gal) activity induced by periadventitial application of CaCl2 to the abdominal aorta. In vitro, COMP knockdown by small interfering (si) RNA led to the elevation of p53, p21 and p16 as well as SA β-gal activity in VSMCs after H2O2 stimulation. VSMCs isolated from COMP(-/-) mice showed elevated senescence-associated markers expression and supplement of COMP adenovirus to COMP-deficient VSMCs greatly rescued cellular senescence. Taken together, these findings revealed the essential role of COMP in retarding the development of vascular aging and VSMC senescence. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Impact of Integrated Vascular Residencies on Academic Productivity within Vascular Surgery Divisions. (United States)

    Kim, Bradford J; Valsangkar, Nakul P; Liang, Tiffany W; Murphy, Michael P; Zimmers, Teresa A; Bell, Teresa M; Davies, Mark G; Koniaris, Leonidas G


    Changing training paradigms in vascular surgery have been introduced to reduce overall training time. Herein, we sought to examine how shortened training for vascular surgeons may have influenced overall divisional academic productivity. Faculty from the top 55 surgery departments were identified according to National Institutes of Health (NIH) funding. Academic metrics of 315 vascular surgery, 1,132 general surgery, and 2,403 other surgical specialties faculty were examined using institutional Web sites, Scopus, and NIH Research Portfolio Online Reporting Tools from September 1, 2014, to January 31, 2015. Individual-level and aggregate numbers of publications, citations, and NIH funding were determined. The mean size of the vascular divisions was 5 faculty. There was no correlation between department size and academic productivity of individual faculty members (R(2) = 0.68, P = 0.2). Overall percentage of vascular surgery faculty with current or former NIH funding was 20%, of which 10.8% had major NIH grants (R01/U01/P01). Vascular surgery faculty associated with integrated vascular training programs demonstrated significantly greater academic productivity. Publications and citations were higher for vascular surgery faculty from institutions with both integrated and traditional training programs (48 of 1,051) compared to those from programs with integrated training alone (37 of 485) or traditional fellowships alone (26 of 439; P productivity was improved within vascular surgery divisions with integrated training programs or both program types. These data suggest that the earlier specialization of integrated residencies in addition to increasing dedicated vascular training time may actually help promote research within the field of vascular surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Hydrogen Delivery Technical Team Roadmap

    Energy Technology Data Exchange (ETDEWEB)



    The mission of the Hydrogen Delivery Technical Team (HDTT) is to enable the development of hydrogen delivery technologies, which will allow for fuel cell competitiveness with gasoline and hybrid technologies by achieving an as-produced, delivered, and dispensed hydrogen cost of $2-$4 per gallon of gasoline equivalent of hydrogen.

  11. Imaging of vascular tumors with an emphasis on ISSVA classification. (United States)

    Nozaki, Taiki; Matsusako, Masaki; Mimura, Hidefumi; Osuga, Keigo; Matsui, Mizuko; Eto, Hikaru; Ohtake, Naoyuki; Manabe, Atsushi; Kusakawa, Isao; Tsutsumi, Yoshiyuki; Nosaka, Shunsuke; Kamo, Minobu; Saida, Yukihisa


    The International Society for the Study of Vascular Anomalies (ISSVA) classification is becoming the international standard classification system for vascular tumors and vascular malformations. The ISSVA classification strictly distinguishes vascular tumors (neoplastic lesions) from vascular malformations (non-neoplastic lesions) based on whether there is a proliferation of vascular endothelial cells present, and it is an extremely useful classification system for determining therapeutic measures. For vascular tumors, it is clinically significant in terms of discriminating infantile hemangioma and rapidly involuting congenital hemangioma, which are expected to spontaneously regress, from other vascular tumors requiring treatment. Needless to say, clinical courses are important for diagnosis, and it is also important for radiologists to understand imaging findings on vascular tumors because such tumors have unique findings on diagnostic images. In this paper, vascular tumors are classified based on the ISSVA classification, and clinical and imaging findings are reviewed.

  12. Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery


    Rocas Alonso, Pau


    [eng] This thesis, entitled "Multifunctional Self-stratified Polyurethane-Polyurea Nanosystems for Smart Drug Delivery" is structured as a compendium of publications, being organized around a methodological synthetic patent and four internationally peer reviewed publications on the chemical and bio-applicability of the US and EU patented invention. Thus, this manuscript is divided into a General Introduction to drug delivery with polyurethane-polyurea nanosystems and three chapters, which inc...

  13. Increased oxygen free radical production during pregnancy may impair vascular reactivity in preeclamptic women. (United States)

    Watanabe, Kazushi; Mori, Toshitaka; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Shinohara, Koichi; Wakatsuki, Akihiko


    To determine whether enhanced oxidative stress during pregnancy impairs vascular endothelial function and improves after delivery in preeclamptic women, we measured serum parameters of oxidative stress and endothelial function during pregnancy and 1 month after delivery in women with or without preeclampsia. We evaluated 18 participants with uncomplicated pregnancies, 11 with mild preeclampsia and 13 with severe preeclampsia. The plasma concentrations of reactive oxygen metabolite derivatives (d-ROMs) were measured, and the biological antioxidant potential (BAP) was determined to evaluate the oxygen free radicals and antioxidants, respectively. Flow-mediated vasodilation (FMD) was also assessed as a marker of endothelial function. FMD was decreased significantly in both preeclamptic groups compared with control during pregnancy. FMD did not change after delivery in the control group, but it significantly increased after delivery in both the mildly and severely preeclamptic groups, nearing control levels 1 month after delivery (mild, 6.5±3.6-9.0±3.5%; severe, 4.3±3.3-9.7±2.6%). No changes in d-ROM concentrations were observed in the control group; however, the concentrations in both the mildly and severely preeclamptic groups significantly decreased to normal levels 1 month after delivery (mild, 562.0±106.5-430.5±90.5 CARR U (Carratelli units); severe, 681.0±239.0-411.8±69.7 CARR U). The plasma BAP levels did not change significantly in all three groups. A negative correlation between FMD and d-ROM concentrations was observed in the preeclamptic group, but not in the control group (r=-0.497; Ppregnancy may impair endothelial function and improve after delivery in preeclamptic women.

  14. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection. (United States)

    Cowan, Douglas B; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R; Thedsanamoorthy, Jerusha K; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; Del Nido, Pedro J; Packard, Alan B; McCully, James D


    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  15. Shifting norms: pregnant women's perspectives on skilled birth attendance and facility-based delivery in rural Ghana. (United States)

    Crissman, Halley P; Engmann, Cyril E; Adanu, Richard M; Nimako, Doris; Crespo, Keesha; Moyer, Cheryl A


    Skilled birth attendance (SBA) and healthcare facility (HCF) delivery are effective means of reducing maternal mortality. However, their uptake remains low in many low-income countries. The present study utilized semi-structured interviews with 85 pregnant women attending an antenatal clinic in Akwatia, Ghana (May-July 2010) to better understand the barriers to SBA and HCF delivery through the underrepresented perspective of pregnant women. Interview transcripts were analyzed using grounded theory methodology. Participants described community support for and uptake of HCF delivery as increasing and becoming normalized, but barriers remain: (1) maltreatment by midwives; (2) cost associated with HCF delivery despite waived facility fees; (3) the need for a support person for HCF delivery; (4) difficulties in transportation; and (5) precipitous labor. Given the importance of community in Ghanaian health care decision-making, increasing community support for HCF delivery suggests progress toward increasing uptake of SBA and HCF delivery, however important actionable barriers remain.

  16. Sirtuins, Cell Senescence, and Vascular Aging. (United States)

    Kida, Yujiro; Goligorsky, Michael S


    The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition; and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, and contribute to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and nicotinamide adenine dinucleotide stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  17. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease


    Kanhai, D.A.N.I.S.


    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society, which is attributable to better disease awareness, better preventive strategies and better healthcare systems. As mortality rates are decreasing, the number of patients surviving their first vascul...

  18. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption (United States)


    Bautista -Sanchez A, Kasselouri A, Desroches MC, Blais J, Maillard P, de Oliveira DM, Tedesco AC, Prognon P, Delaire J. Photophysical properties of... Ramirez -San-Juan JC, Nelson JS, Osann K, Kelly KM. Microvascular blood flow dynamics associated with photody- namic therapy, pulsed dye laser

  19. Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging. (United States)

    Serrat, Maria A; Efaw, Morgan L; Williams, Rebecca M


    Advances in understanding the molecular regulation of longitudinal growth have led to development of novel drug therapies for growth plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents to avascular-cartilage plates. Dense extracellular matrix and lack of penetrating blood vessels create a semipermeable "barrier," which hinders molecular transport at the vascular-cartilage interface. To overcome this obstacle, we used a hindlimb heating model to manipulate bone circulation in 5-wk-old female mice (n = 22). Temperatures represented a physiological range of normal human knee joints. We used in vivo multiphoton microscopy to quantify temperature-enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22°C to 34°C increases vascular access of large systemic molecules, modeled using 10, 40, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from subperichondrial plexus vessels and accumulation in growth plate cartilage. Growth plate entry of 10 kDa dextrans increased >150% at 34°C. Entry of 40 and 70 kDa dextrans increased vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive strategy for modulating delivery of therapeutics to impaired growth plates of children.

  20. Exocrine drainage in vascularized pancreas transplantation in the new millennium (United States)

    El-Hennawy, Hany; Stratta, Robert J; Smith, Fowler


    The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to re-create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported

  1. [Subsequent pregnancy outcomes after first pregnancy with severe preeclampsia and delivery before 34 weeks of gestation]. (United States)

    Lemonnier, M; Beucher, G; Morello, R; Herlicoviez, M; Dreyfus, M; Benoist, G


    Women who had severe preeclampsia are at high risk of gestational vascular complications (preeclampsia, gestational hypertension, fetal death, small for gestational age, placenta abruptio) in subsequent pregnancies. The aim of this study was to describe outcomes of subsequent pregnancy after severe preeclampsia with delivery before 34 weeks of gestation during the first pregnancy. One hundred and thirty-four primiparous women delivered before 34 weeks of gestation resulting in severe preeclampsia between January 2002 and December 2009. The data of the index pregnancy were identified from the medical record of our maternity, those of the subsequent pregnancy from paper or computerized medical records of the hospitals where deliveries took place. Our study ended on December 31 2011 for a decrease of at least 2 years after the index pregnancy. Of the 75 subsequent pregnancies, 59 have been studied. Twenty patients (34%) had gestational vascular complications, in type of gestational hypertension alone (10%), preeclampsia (65%), isolated small for gestational age (20%) or fetal death (5%). Thirty-nine patients (66%) showed no recurrence of gestational vascular complications but only 33 patients (56%) had a pregnancy of course totally physiological. The only risk factor for recurrent gestational vascular complications in subsequent pregnancy was a long time interval between two pregnancies, with an increased risk in case of delay beyond 26 months. Women with a history of severe preeclampsia with delivery before 34 weeks of gestation during first pregnancy are at increased risk for gestational vascular complications during the next pregnancy. A close obstetrical monitoring is recommended during a subsequent pregnancy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Bibliometric analysis of factors predicting increased citations in the vascular and endovascular literature. (United States)

    Antoniou, George A; Antoniou, Stavros A; Georgakarakos, Efstratios I; Sfyroeras, George S; Georgiadis, George S


    Dissemination of research findings in the scientific community is reflected by the citation count. Our objective was to investigate the relative citation impact of vascular research studies and identify potential predictors of increased citation rates. Articles published in leading journals of vascular and general surgery (Journal of Vascular Surgery, European Journal of Vascular and Endovascular Surgery, Journal of Endovascular Therapy, Annals of Vascular Surgery and Annals of Surgery, British Journal of Surgery, Journal of the American College of Surgeons, and JAMA Surgery) during a 4-month period were identified through electronic databases. Variables potentially associated with increased citation rates, including subject, design, title characteristics, article length, bibliographic references, authorship, geographic distribution, interdisciplinary collaboration, article access, and funding, were assessed in univariate and multiple linear regression models through December 2012. A total of 226 articles with a total number of 4,605 citations were identified. Univariate analysis revealed that endovascular-related studies, study design, studies reporting design in the title, long articles, and studies with high number of references were associated with higher citation rates. On multivariate analysis, 3 variables were found to independently predict the number of citations: study subject (endovascular-related studies; regression coefficient [95% confidence interval], 0.474 [0.240-0.708]; P < 0.001); study design (randomized controlled trial; regression coefficient [95% confidence interval], 0.575 [0.145-1.005]; P = 0.009); and article length (number of pages; regression coefficient [95% confidence interval], 0.069 [0.016-0.123]; P = 0.011). Authors involved in vascular research may enhance the impact of their work by embarking on research strategies of high methodologic quality and pursuing work related with new technologies and evolving endovascular therapies

  3. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter


    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  4. Nanotoxicology materials, methodologies, and assessments

    CERN Document Server

    Durán, Nelson; Alves, Oswaldo L; Zucolotto, Valtencir


    This book begins with a detailed introduction to engineered nanostructures, followed by a section on methodologies used in research on cytotoxicity and genotoxicity, and concluding with evidence for the cyto- and genotoxicity of specific nanoparticles.

  5. Environmental probabilistic quantitative assessment methodologies (United States)

    Crovelli, R.A.


    In this paper, four petroleum resource assessment methodologies are presented as possible pollution assessment methodologies, even though petroleum as a resource is desirable, whereas pollution is undesirable. A methodology is defined in this paper to consist of a probability model and a probabilistic method, where the method is used to solve the model. The following four basic types of probability models are considered: 1) direct assessment, 2) accumulation size, 3) volumetric yield, and 4) reservoir engineering. Three of the four petroleum resource assessment methodologies were written as microcomputer systems, viz. TRIAGG for direct assessment, APRAS for accumulation size, and FASPU for reservoir engineering. A fourth microcomputer system termed PROBDIST supports the three assessment systems. The three assessment systems have different probability models but the same type of probabilistic method. The type of advantages of the analytic method are in computational speed and flexibility, making it ideal for a microcomputer. -from Author

  6. Some notes on taxonomic methodology

    NARCIS (Netherlands)

    Hammen, van der L.


    The present paper constitutes an introduction to taxonomic methodology. After an analysis of taxonomic practice, and a brief survey of kinds of attributes, the paper deals with observation, description, comparison, arrangement and classification, hypothesis construction, deduction, model,

  7. An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback. (United States)

    Chang, Yen-Chi; Berry-Pusey, Brittany; Yasin, Rashid; Vu, Nam; Maraglia, Brandon; Chatziioannou, Arion X; Tsao, Tsu-Chin


    This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system.

  8. Design and development of multilayer vascular graft (United States)

    Madhavan, Krishna


    Vascular graft is a widely-used medical device for the treatment of vascular diseases such as atherosclerosis and aneurysm as well as for the use of vascular access and pediatric shunt, which are major causes of mortality and morbidity in this world. Dysfunction of vascular grafts often occurs, particularly for grafts with diameter less than 6mm, and is associated with the design of graft materials. Mechanical strength, compliance, permeability, endothelialization and availability are issues of most concern for vascular graft materials. To address these issues, we have designed a biodegradable, compliant graft made of hybrid multilayer by combining an intimal equivalent, electrospun heparin-impregnated poly-epsilon-caprolactone nanofibers, with a medial equivalent, a crosslinked collagen-chitosan-based gel scaffold. The intimal equivalent is designed to build mechanical strength and stability suitable for in vivo grafting and to prevent thrombosis. The medial equivalent is designed to serve as a scaffold for the activity of the smooth muscle cells important for vascular healing and regeneration. Our results have shown that genipin is a biocompatible crosslinker to enhance the mechanical properties of collagen-chitosan based scaffolds, and the degradation time and the activity of smooth muscle cells in the scaffold can be modulated by the crosslinking degree. For vascular grafting and regeneration in vivo, an important design parameter of the hybrid multilayer is the interface adhesion between the intimal and medial equivalents. With diametrically opposite affinities to water, delamination of the two layers occurs. Physical or chemical modification techniques were thus used to enhance the adhesion. Microscopic examination and graft-relevant functional characterizations have been performed to evaluate these techniques. Results from characterization of microstructure and functional properties, including burst strength, compliance, water permeability and suture

  9. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Sevostyanova, V. V., E-mail:; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation)


    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  10. A Probabilistic Ontology Development Methodology (United States)


    Journal of Human-Computer Studies, pp. 907-928, 1995. [8] Grigoris Antoniou and Frank Van Harmelen, "Web Ontology Language: OWL," in Handbook on...Probabilistic Ontology Development Methodology Topic 3: Data, Information,and Knowledge Topic 5: Modeling and Simulation Topic 7: Autonomy...2014 to 00-00-2014 4. TITLE AND SUBTITLE A Probabilistic Ontology Development Methodology 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  11. Methodology scuba diving on tinge


    Vondrášek, David


    Title: Methodology of apnea diving Objectives: The main objective of this work is to develop materials that could serve as a learning support students in basic studies of apnea diving. A part of the history of diving equipment and diving physiology of flavor and also methodologies apnea diving. Methods: Study of available sources. Literature available sources. Development of educational material using the material used and its own experience. Results: The result is a learning support for stud...


    Directory of Open Access Journals (Sweden)

    A. Stepanov


    Full Text Available The issues of vehicle safety are considered. The methodology of approach to analyzing and solving the problem of safety management of vehicles and overall traffic is offered. The distinctive features of organization and management of vehicle safety are shown. There has been drawn a conclusion that the methodological approach to solving traffic safety problems is reduced to selection and classification of safety needs.

  13. Energy Efficiency Indicators Methodology Booklet


    Sathaye, Jayant


    This Methodology Booklet provides a comprehensive review and methodology guiding principles for constructing energy efficiency indicators, with illustrative examples of application to individual countries. It reviews work done by international agencies and national government in constructing meaningful energy efficiency indicators that help policy makers to assess changes in energy efficiency over time. Building on past OECD experience and best practices, and the knowledge of these countries'...

  14. Blood flow restricted exercise and vascular function. (United States)

    Horiuchi, Masahiro; Okita, Koichi


    It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR) leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  15. Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

    Directory of Open Access Journals (Sweden)

    Wang J


    Full Text Available Jingli Wang,1 Michael E Widlansky1,21Department of Medicine, Cardiovascular Medicine Division, 2Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin, USAAbstract: Far from being inert, the vascular endothelium is a critical regulator of vascular function. While the endothelium participates in autocrine, paracrine, and endocrine signaling, it also transduces mechanical signals from the cell surface involving key cell structural elements. In this review, we discuss the structure of the vascular endothelium and its relationship to traditional cardiovascular risk factors and clinical cardiovascular events. Further, we review the emerging evidence that cell structural elements, including the glycocalyx, intercellular junctions, and cytoskeleton elements, help the endothelium to communicate with its environment to regulate vascular function, including vessel permeability and signal transduction via nitric oxide bioavailability. Further work is necessary to better delineate the regulatory relationships between known key regulators of vascular function and endothelial cell structural elements.Keywords: endothelium, shear stress, eNOS, cardiovascular risk factors, glycocalyx

  16. Toward a pathological definition of vascular dementia. (United States)

    Grinberg, Lea Tenenholz; Heinsen, Helmut


    To date, there are no widely accepted neuropathological criteria for vascular dementia, although creating such a standard is ranked high on the wish list of all the researchers in this field. Such criteria would make it possible to perform large multicentre clinicopathological studies and, consequently, to better understand which, how, and where vascular brain lesions lead to cognitive decline, as it is possible to do in Alzheimer's disease or Parkinson's disease. However, a major obstacle in the standardization of diagnosis is the fact that vascular brain lesions are a large group comprising heterogeneous changes that have different pathogeneses. Although it is accepted that some kinds of vascular changes cause cognitive impairment, it is not uncommon to find reports of the assumed same histological changes in control subjects. An indispensable first step in the unequivocal establishment of neuropathological criteria is to uniform the definitions used for each one of the lesions, preferably based on its pathogenesis. In the present, non-standardized state of ambiguity, a given lesion is designated by different names between and within the clinical, radiological, and pathological settings, and several definitions simply overlap. Before attempting to create new criteria, a multidisciplinary group-task is urged to identify and minimize the uncontrolled proliferation of definitions. Only then, it will be possible to advance the understanding of how vascular brain changes affect cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi


    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  18. Electronic Nicotine Delivery Systems. (United States)

    Walley, Susan C; Jenssen, Brian P


    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

  19. T cells enhance gold nanoparticle delivery to tumors in vivo (United States)

    Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.


    Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  20. Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND)


    Stephan, BCM; Minett, T.; Muniz-Terrera, G.; Harrison, SL; Matthews, FE; Brayne, C.


    $\\textbf{Background}$ vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. $\\textbf{Objective}$ to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Ri...

  1. Vascular effects of maternal alcohol consumption. (United States)

    Ramadoss, Jayanth; Magness, Ronald R


    Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.

  2. Roles of xenobiotic receptors in vascular pathophysiology. (United States)

    Xiao, Lei; Zhang, Zihui; Luo, Xiaoqin


    The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. They are hence defined as "xenobiotic receptors". Recent studies have demonstrated that PXR, CAR and AhR also regulate the expression of key proteins involved in endobiotic responses such as the metabolic homeostasis of lipids, glucose, and bile acid, and inflammatory processes. It is suggested that the functions of PXR, CAR and AhR may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension. Therefore, manipulation of the activities of these receptors may provide novel strategies for the treatment of vascular diseases. Here, we review the pathophysiological roles of PXR, CAR and AhR in the vascular system.

  3. Nonsurgical management of vascular malformation of masseter

    Directory of Open Access Journals (Sweden)

    Venkatesh Jayaraman


    Full Text Available Intramuscular vascular anomalies are rare congenital hamartomatous lesions. Less than 1% of these occur in skeletal muscle out of which 15% arise in head and neck musculature. In the head and neck region, masseter muscle is the most common site. It accounts for about 5% of intramuscular vascular malformations. They are present from birth but are clinically apparent during infancy and childhood and occasionally during adulthood. Due to its location it is often mistaken for a parotid swelling. The usual treatment of choice is surgical excision with a margin. This is associated with loss of motor function, hemorrhage, nerve damage. Intralesional sclerotherapy, embolization are nonsurgical alternatives for treatment of slow flow venous malformations. Sclerotherapy can be used solely in multiple sittings or as an adjunct to surgery. This article presents a case report of a 28-year-old male with recurrent intramuscular vascular malformation in the masseter muscle, which was successfully treated by ethanol sclerotherapy.

  4. Vascular permeability in cerebral cavernous malformations

    DEFF Research Database (Denmark)

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao


    -controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability...... vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy....... correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive...

  5. Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia (United States)

    Baker, Christopher D.; Abman, Steven H.


    Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with preterm birth, results from disruption of normal pulmonary vascular and alveolar growth. Though BPD was once described as primarily due to postnatal injury from mechanical ventilation and oxygen therapy after preterm birth, it is increasingly appreciated that BPD results from antenatal and perinatal factors that interrupt lung development in infants born at the extremes of prematurity. The lung in BPD consists of a simplified parenchymal architecture that limits gas exchange and leads to increased cardiopulmonary morbidity and mortality. This review outlines recent advances in the understanding of pulmonary vascular development and describes how disruption of these mechanisms results in BPD. We point to future therapies that may augment postnatal vascular growth to prevent and treat this severe chronic lung disease. PMID:26044102

  6. Space age health care delivery (United States)

    Jones, W. L.


    Space age health care delivery is being delivered to both NASA astronauts and employees with primary emphasis on preventive medicine. The program relies heavily on comprehensive health physical exams, health education, screening programs and physical fitness programs. Medical data from the program is stored in a computer bank so epidemiological significance can be established and better procedures can be obtained. Besides health care delivery to the NASA population, NASA is working with HEW on a telemedicine project STARPAHC, applying space technology to provide health care delivery to remotely located populations.

  7. New developments in insulin delivery. (United States)

    Khan Ghilzai, Naushad M


    A vigorous research effort has been undertaken worldwide to replace injectable insulin by a more comfortable and painless delivery method. Several routes have been explored for their suitability with respect to insulin degradation in the human body. Considerable progress has been made in achieving the common goal for a convenient and equally effective insulin delivery. This article reviews the different routes available for insulin administration and the many successful developments that have been made in recent years for improving that particular route for a much better insulin delivery.

  8. Delivery technologies for genome editing. (United States)

    Yin, Hao; Kauffman, Kevin J; Anderson, Daniel G


    With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials.

  9. Yield enhancement methodologies for 90-nm technology and beyond (United States)

    Allgair, John; Carey, Todd; Dougan, James; Etnyre, Tony; Langdon, Nate; Murray, Brooke


    In order to stay competitive in the rapidly advancing international semiconductor industry, a manufacturing company needs to continually focus on several areas including rapid yield learning, manufacturing cost, statistical process control limits, process yield, equipment availability, cycle time, turns per direct labor hour, customer on time delivery and zero customer defects. To hold a competitive position in the semiconductor market, performance to these measurable factors mut be maintained regardless of the technology generation. In this presentation, the methodology applied by Freescale Semiconductor to achieve the fastest yield learning curve in the industry, as cited by Dr. Robert Leachman of UC Berkley in 2003, will be discussed.

  10. Ultrasound for vascular access in pediatric patients. (United States)

    Schindler, Ehrenfried; Schears, Gregory J; Hall, Stuart R; Yamamoto, Tomohiro


    In pediatric patients vascular access is often more difficult than in adults because of the smaller size of the vessels and the inability of the patient to cooperate without deep sedation or general anesthesia. Therefore Ultrasound has already become an invaluable tool for vascular access, but the full potential of ultrasound has yet to be fully realized. Improvements in image quality and a better understanding of optimal insertion techniques continue to help clinicians safely and efficiently place catheters with fewer complications. The probes used for the vascular access are mainly linear and convex type. Higher- frequency ultrasound provides a vivid image; however, the signals are remarkably attenuated. Therefore, the choice of the probe with appropriate frequency is essential. As blood vessels are relatively easily identified with ultrasound, ultrasound-guided vascular access does not require as sharp images as ultrasound-guided nerve block. For pediatric vascular access, the linear probe with 5-15 MHz, 2-5 cm depth is ideal and adequate for almost all cases. Ultrasound-guided vascular access has two main approaches: 'long-axis' or 'in-plane approach' and 'short-axis' or 'transverse approach'. The long-axis approach visualizes the vessel along the insertion pathway and is commonly used to monitor the entire approach of the needle into the vessel. The short-axis approach is easier to show the positional relationship and depth of target vessels, but it is much harder to follow the needle tip within the tissues. The use of 'real-time' ultrasound has been shown to increase first insertion success, reduce access time, have a higher overall success, and reduce arterial puncture. As the technology continues to improve the use of ultrasound will become as ubiquitous as the lines themselves. © 2012 Blackwell Publishing Ltd.

  11. Oxidative stress and vascular inflammation in aging. (United States)

    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio


    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  12. Sulforaphane inhibits restenosis by suppressing inflammation and the proliferation of vascular smooth muscle cells. (United States)

    Kwon, Jin-Sook; Joung, Hosouk; Kim, Yong Sook; Shim, Young-Sun; Ahn, Youngkeun; Jeong, Myung Ho; Kee, Hae Jin


    Sulforaphane, a naturally occurring organosulfur compound in broccoli, has chemopreventive properties in cancer. However, the effects of sulforaphane in vascular diseases have not been examined. We therefore aimed to investigate the effects of sulforaphane on vascular smooth muscle cell (VSMC) proliferation and neointimal formation and the related mechanisms. The expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) was examined in VSMCs. The nuclear translocation of nuclear factor-κB (NF-κB) and GATA6 expression was examined in VSMCs and in a carotid artery injury model by Western blot and immunohistochemistry. We also investigated whether local delivery of sulforaphane affected neointimal formation. Sulforaphane inhibited the mRNA and protein expression of VCAM-1 induced by tumor necrosis factor (TNF)-α in VSMCs. Treatment of VSMCs with sulforaphane blocked TNF-α-induced IκBα degradation and NF-κB p65 and GATA6 expression. Furthermore, NF-κB p65 and GATA6 expression were reduced in sulforaphane-treated carotid injury sections. Notably, binding of GATA6 to the VCAM-1 promoter was dramatically reduced by sulforaphane. The MTT, BrdU incorporation, and in vitro scratch assays revealed that the proliferation and migration of VSMCs were reduced by sulforaphane. Furthermore, local administration of sulforaphane significantly reduced neointima formation 14 days after vascular injury in rats. Our results indicate that sulforaphane inhibits neointima formation via targeting of adhesion molecules through the suppression of NF-κB/GATA6. Furthermore, sulforaphane regulates migration and proliferation in VSMCs. Sulforaphane may be a potential therapeutic agent for preventing restenosis after vascular injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model (United States)

    Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi


    Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular

  14. [Sonography of vascular and biliary epigastric structures]. (United States)

    Triller, J; Haertel, M; Zaunbauer, W; Fuchs, W A


    Ultrasonic devices with rapid image build-up and high power of resolution enable detailed assessment of the vascular and biliary structures. Visualisation of the biliary tract of normal lumen in the extrahepatic region enables identification of a biliary obstruction at a time where dilatation of the intrahepatic biliary tract has not yet taken place. The identification of small visceral branches of the aorta abdominalis as well as of portal and systemic veins yields sonographically reliable vascular points of reference which enable, apart from the exact localisation of the biliary tract and of the pancreas, accurate topographic identification of abdominal mass lesions.

  15. Genealogy of training in vascular neurosurgery. (United States)

    Chowdhry, Shakeel A; Spetzler, Robert F


    Remarkable advances and changes in the landscape of neurovascular disease have occurred recently. Concurrently, a paradigm shift in training and resident education is underway. This crossroad of unique opportunities and pressures necessitates creative change in the training of future vascular neurosurgeons to allow incorporation of surgical advances, new technology, and supplementary treatment modalities in a setting of reduced work hours and increased public scrutiny. This article discusses the changing landscape in neurovascular disease treatment, followed by the recent changes in resident training, and concludes with our view of the future of training in vascular neurosurgery.

  16. Laser speckle analysis of retinal vascular dynamics

    DEFF Research Database (Denmark)

    Neganova, Anastasiia Y.; Postnov, Dmitry D.; Jacobsen, Jens Christian B.


    Studies of vascular responses are usually performed on isolated vessels or on single vessels in vivo. This allows for precise measurements of diameter or blood flow. However, dynamical responses of the whole microvascular network are difficult to access experimentally. We suggest to use full......-field laser speckle imaging to evaluate vascular responses of the retinal network. Image segmentation and vessel recognition algorithms together with response mapping allow us to analyze diameter changes and blood flow responses in the intact retinal network upon systemic administration of the vasoconstrictor...

  17. Gastric antral vascular ectasia: a case report

    Directory of Open Access Journals (Sweden)

    Amir Cehajic


    Full Text Available Gastric antral vascular ectasia is a vascular gastric malformation which represents a rare cause of upper gastrointestinal system bleeding. It is usually presented with a significant anemia and it is diagnosed with an endoscopic examination of the upper gastrointestinal system. It is often associated with other chronic illnesses such as liver cirrhosis, sclerodermia, diabetes mellitus and arterial hypertension. It is treated symptomatically in terms of anemia correction with blood transfusions and iron supplements, proton pump inhibitors, beta-blockers and endoscopic procedures such as argon plasma coagulation which currently represents the treatment of choice in Sy. GAVE cases.

  18. Prediction of Major Vascular Events after Stroke

    DEFF Research Database (Denmark)

    Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre


    BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination...

  19. Delivery of large biopharmaceuticals from cardiovascular stents: a review. (United States)

    Takahashi, Hironobu; Letourneur, Didier; Grainger, David W


    This review focuses on new and emerging large-molecule bioactive agents delivered from stent surfaces in drug-eluting stents (DESs) to inhibit vascular restenosis in the context of interventional cardiology. New therapeutic agents representing proteins, nucleic acids (small interfering RNAs and large DNA plasmids), viral delivery vectors, and even engineered cell therapies require specific delivery designs distinct from traditional smaller-molecule approaches on DESs. While small molecules are currently the clinical standard for coronary stenting, extension of the DESs to other lesion types, peripheral vasculature, and nonvasculature therapies will seek to deliver an increasingly sophisticated armada of drug types. This review describes many of the larger-molecule and biopharmaceutical approaches reported recently for stent-based delivery with the challenges associated with formulating and delivering these drug classes compared to the current small-molecule drugs. It also includes perspectives on possible future applications that may improve safety and efficacy and facilitate diversification of the DESs to other clinical applications.

  20. The Joint Commission Ever-Readiness: Understanding Tracer Methodology. (United States)

    Siewert, Bettina


    The Joint Commission (TJC) evaluates the consistent provision of appropriate and safe access to health care, treatment, and services. Currently, TJC uses the tracer methodology to assess standards compliance and follows a number of patients through an organization's entire health care delivery process. The tracer methodology uses 3 different types of tracers as follows: individual or patient tracers, program-specific, and system tracers, to identify performance issues in one or more steps of the care process or at interfaces between them. This review article describes the different types of tracers used by TJC and provides examples of each tracer in radiology; it outlines how to achieve TJC ever-readiness with the use of mock tracers and provides practical suggestions on how to ensure staff engagement. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Plasma protein corona modulates the vascular wall interaction of drug carriers in a material and donor specific manner.

    Directory of Open Access Journals (Sweden)

    Daniel J Sobczynski

    Full Text Available The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid (PLGA spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.

  2. Concurrent anti-vascular therapy and chemotherapy in solid tumors using drug-loaded acoustic nanodroplet vaporization. (United States)

    Ho, Yi-Ju; Yeh, Chih-Kuang


    Drug-loaded nanodroplets (NDs) can be converted into gas bubbles through ultrasound (US) stimulation, termed acoustic droplet vaporization (ADV), which provides a potential strategy to simultaneously induce vascular disruption and release drugs for combined physical anti-vascular therapy and chemotherapy. Doxorubicin-loaded NDs (DOX-NDs) with a mean size of 214nm containing 2.48mg DOX/mL were used in this study. High-speed images displayed bubble formation and cell debris, demonstrating the reduction in cell viability after ADV. Intravital imaging provided direct visualization of disrupted tumor vessels (vessel size chemotherapy with DOX-NDs vaporization promotes uniform treatment to improve therapeutic efficacy. Tumor vasculature plays an important role for tumor cell proliferation by transporting oxygen and nutrients. Previous studies combined anti-vascular therapy and drug release to inhibit tumor growth by ultrasound-stimulated microbubble destruction or acoustic droplet vaporization. Although the efficacy of combined therapy has been demonstrated; the relative spatial distribution of vascular disruption, drug delivery, and accompanied immune responses within solid tumors was not discussed clearly. Herein, our study used drug-loaded nanodroplets to combined physical anti-vascular and chemical therapy. The in vitro cytotoxicity, intravital imaging, and histological assessment were used to evaluate the temporal and spatial cooperation between physical and chemical effect. These results revealed some evidences for complementary action to explain the high efficacy of tumor inhibition by combined therapy. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering. (United States)

    Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song


    Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

  4. Adenosine-Associated Delivery Systems (United States)

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali


    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  5. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T


    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  6. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC


    Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.

  7. Continuous Delivery and Quality Monitoring

    CERN Multimedia

    CERN. Geneva


    After introducing Continuous Delivery, I will switch the topic and try to answer the question how much should we invest in quality and how to do it efficiently. My observations reveal that software quality is often considered as the slo...

  8. Assessment of risk of peripheral vascular disease and vascular care capacity in Ghana (United States)

    Gyedu, Adam; Stewart, Barclay T; Nakua, Emmanuel; Quansah, Robert; Donkor, Peter; Mock, Charles; Hardy, Mark A; Yangni-Angate, Koffi Herve


    Introduction This study aimed to describe national peripheral vascular disease (PVD) risk and health burden and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in a low- and middle-income country (LMIC) is defined and capacity improvement priorities identified. Methods Data to estimate PVD risk factor burden were obtained from: i) World Health Organization’s Study on Global Ageing and Health (SAGE), Ghana; and ii) Institute of Health Metrics and Evaluation Global Burden of Disease database (IHME GBD). In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were also described. Results From the SAGE database, there were 4,305 respondents aged at least 50 years with data to estimate PVD risk. Out of these 57% were at moderate to high PVD risk with ≥3 risk factors, thus giving 1,654,557 persons when extrapolated nationally. Using IHME GBD data, the estimated disability-adjusted life years incurred from PVD increased 5-fold from 1990 to 2010 (1.3 to 3.2 per 100,000 persons, respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. Conclusion Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of peripheral vascular disease falling on healthcare systems in low- and middle-income countries that are not well equipped to handle vascular surgical care, and for which rapid development of such capacity would be difficult and expensive. PMID:26560502

  9. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies. (United States)

    Wassef, Michel; Blei, Francine; Adams, Denise; Alomari, Ahmad; Baselga, Eulalia; Berenstein, Alejandro; Burrows, Patricia; Frieden, Ilona J; Garzon, Maria C; Lopez-Gutierrez, Juan-Carlos; Lord, David J E; Mitchel, Sally; Powell, Julie; Prendiville, Julie; Vikkula, Miikka


    Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists. Classification schemes provide a consistent terminology and serve as a guide for pathologists, clinicians, and researchers. One of the goals of the International Society for the Study of Vascular Anomalies (ISSVA) is to achieve a uniform classification. The last classification (1997) stratified vascular lesions into vascular malformations and proliferative vascular lesions (tumors). However, additional disease entities have since been identified that are complex and less easily classified by generic headings, such as capillary malformation, venous malformation, lymphatic malformation, etc. We hereby present the updated official ISSVA classification of vascular anomalies. The general biological scheme of the classification is retained. The section on tumors has been expanded and lists the main recognized vascular tumors, classified as benign, locally aggressive or borderline, and malignant. A list of well-defined diseases is included under each generic heading in the "Simple Vascular Malformations" section. A short definition is added for eponyms. Two new sections were created: one dealing with the malformations of individually named vessels (previously referred to as "truncular" malformations); the second groups lesions of uncertain or debated nature (tumor versus malformation). The known genetic defects underlying vascular anomalies are included in an appendix. This classification is meant to be a framework, acknowledging that it will require modification as new scientific information becomes available. Copyright © 2015 by the American Academy of Pediatrics.

  10. Vascular plugs - A key companion to Interventionists - 'Just Plug it'. (United States)

    Ramakrishnan, Sivasubramanian


    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

  11. Vascular cognitive impairment (VCI: Progress towards knowledge and treatment

    Directory of Open Access Journals (Sweden)

    Silvia Di Legge

    Full Text Available Abstract Until recently, the study of cognitive impairment as a manifestation of cerebrovascular disease (CVD has been hampered by the lack of common standards for assessment. The term vascular cognitive impairment (VCI encompasses all levels of cognitive decline associated with CVD from mild deficits in one or more cognitive domains to crude dementia syndrome. VCI incorporates the complex interactions among classic vascular risk factors (i.e. arterial hypertension, high cholesterol, and diabetes, CVD subtypes, and Alzheimer's Disease (AD pathology. VCI may be the earliest, commonest, and subtlest manifestation of CVD and can be regarded as a highly prevalent and preventable syndrome. However, cognition is not a standardized outcome measure in clinical trials assessing functional ability after stroke. Furthermore, with the exception of anti-hypertensive medications, the impact of either preventive or acute stroke treatments on cognitive outcome is not known. Although clinical, epidemiological, neuroimaging, and experimental data support the VCI concept, there is a lack of integrated knowledge on the role played by the most relevant pathophysiological mechanisms involved in several neurological conditions including stroke and cognitive impairment such as excitotoxicity, apoptosis, mitochondrial DNA damage, oxidative stress, disturbed neurotransmitter release, and inflammation. For this reason, in 2006 the National Institute of Neurological Disorders and Stroke (NINDS and the Canadian Stroke Network (CSN defined a set of data elements to be collected in future studies aimed at defining VCI etiology, clinical manifestations, predictive factors, and treatment. These recommendations represent the first step toward developing diagnostic criteria for VCI based on sound knowledge rather than on hypotheses. The second step will be to integrate all studies using the agreed methodologies. This is likely to accelerate the search for answers.

  12. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling (United States)

    Parsons-Wingerter, Patricia


    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  13. Development of insulin delivery systems. (United States)

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A


    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems.

  14. Degradable Polymers for Gene Delivery (United States)

    Sunshine, Joel; Bhise, Nupura; Green, Jordan J.


    Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure led to significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than Lipofectamine 2000 or polyethylenimine for gene delivery to cancerous fibroblasts or human primary fibroblasts. These materials may be useful for cancer therapeutics and regenerative medicine. PMID:19964958

  15. 76 FR 71431 - Civil Penalty Calculation Methodology (United States)


    ... TRANSPORTATION Federal Motor Carrier Safety Administration Civil Penalty Calculation Methodology AGENCY: Federal... its civil penalty methodology. Part of this evaluation includes a forthcoming explanation of the... methodology for calculation of certain civil penalties. To induce compliance with federal regulations, FMCSA...

  16. Gene Delivery into Plant Cells for Recombinant Protein Production

    Directory of Open Access Journals (Sweden)

    Qiang Chen


    Full Text Available Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications.

  17. In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography (United States)

    Liew, Yih Miin; McLaughlin, Robert A.; Gong, Peijun; Wood, Fiona M.; Sampson, David D.


    In scars arising from burns, objective assessment of vascularity is important in the early identification of pathological scarring, and in the assessment of progression and treatment response. We demonstrate the first clinical assessment and automated quantification of vascularity in cutaneous burn scars of human patients in vivo that uses optical coherence tomography (OCT). Scar microvasculature was delineated in three-dimensional OCT images using speckle decorrelation. The diameter and area density of blood vessels were automatically quantified. A substantial increase was observed in the measured density of vasculature in hypertrophic scar tissues (38%) when compared against normal, unscarred skin (22%). A proliferation of larger vessels (diameter≥100 μm) was revealed in hypertrophic scarring, which was absent from normal scars and normal skin over the investigated physical depth range of 600 μm. This study establishes the feasibility of this methodology as a means of clinical monitoring of scar progression.

  18. IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics. (United States)

    Abad, C; Antczak, D F; Carvalho, J; Chamley, L W; Chen, Q; Daher, S; Damiano, A E; Dantzer, V; Díaz, P; Dunk, C E; Daly, E; Escudero, C; Falcón, B; Guillomot, M; Han, Y W; Harris, L K; Huidobro-Toro, J P; Illsley, N; Jammes, H; Jansson, T; Johnson, G A; Kfoury, J R; Marín, R; Murthi, P; Novakovic, B; Myatt, L; Petroff, M G; Pereira, F T V; Pfarrer, C; Redman, C W G; Rice, G; Saffery, R; Tolosa, J M; Vaillancourt, C; Wareing, M; Yuen, R; Lash, G E


    Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Regulator of calcineurin 1 mediates pathological vascular wall remodeling (United States)

    Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.


    Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

  20. MR molecular imaging of tumor vasculature and vascular targets. (United States)

    Pathak, Arvind P; Penet, Marie-France; Bhujwalla, Zaver M


    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from "bench to bedside". The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Acquire uterine vascular malformation: Clinical outcome of transarterial embolization

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Chae Hoon [Dept. of Radiology, Gangneung Asan Hospital, Gangneung (Korea, Republic of); Yang, Seung Boo; Goo, Dong Erk; Kim, Yong Jae; Lee, Jae Myung; Lee, Woong Hee [Dept. of Radiology, Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)


    To evaluate clinical outcomes of transarterial embolization of bilateral uterine arteries (UAE) in patients with acquired uterine vascular malformation (UVM). This retrospective study was performed on the medical records of all 19 patients who underwent transarterial embolization of bilateral UAE for the treatment of symptomatic UVMs from January 2003 to June 2011. Embolization was performed via the unilateral femoral artery approach with a catheter and angiographic techniques. Clinical success was defined as definitive resolution of abnormal vaginal bleeding. Post-procedural complications included all adverse events related to the embolization procedure. A total of 20 procedures were performed in 19 patients. One patient required repeat embolization because of incomplete embolization related to prominent high flow malformation. Clinically, in all patients, bleeding was controlled immediately after embolization. No complications occurred in all patients during the follow up period. In all patients who underwent successful UAE, menstrual cycles were normally restored within 1-2 months. Normal pregnancy with term delivery was observed in two of the 19 cases. Transarterial bilateral UAE is a safe and effective treatment in patients with vaginal bleeding caused by acquired UVM, and it allows the possibility of future pregnancy.

  2. Managerial Methodology in Public Institutions

    Directory of Open Access Journals (Sweden)



    Full Text Available One of the most important ways of making public institutions more efficient is by applying managerial methodology, embodied in the promotion of management tools, modern and sophisticated methodologies, as well as operation of designing/redesigning and maintenance of the management process and its components. Their implementation abides the imprint of constructive and functional particularities of public institutions, decentralized and devolved, and, of course, the managers’ expertise of these organizations. Managerial methodology is addressed through three important instruments diagnosis, management by objectives and scoreboard. Its presence in the performance management process should be mandatory, given the favorable influence on the management and economic performance and the degree of scholastic approach of the managers’ performance.

  3. The NLC Software Requirements Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Shoaee, Hamid


    We describe the software requirements and development methodology developed for the NLC control system. Given the longevity of that project, and the likely geographical distribution of the collaborating engineers, the planned requirements management process is somewhat more formal than the norm in high energy physics projects. The short term goals of the requirements process are to accurately estimate costs, to decompose the problem, and to determine likely technologies. The long term goal is to enable a smooth transition from high level functional requirements to specific subsystem and component requirements for individual programmers, and to support distributed development. The methodology covers both ends of that life cycle. It covers both the analytical and documentary tools for software engineering, and project management support. This paper introduces the methodology, which is fully described in [1].

  4. General versus vascular surgeon: impact of a vascular fellowship on clinical practice, surgical case load, and lifestyle. (United States)

    Franz, Randall W


    An applicant shortage for vascular surgery (VS) residencies exists despite an increase in available training positions created to meet the growing demands for vascular surgeons. After 3 years of practice as an American Board of Surgery (ABS)-certified/board-eligible general surgeon, the author of this study attended an accredited 1-year VS training fellowship and received an ABS certificate of Added Qualifications in VS. The purpose of this review was to investigate the implications completing a vascular fellowship has had on VS procedure patterns, vascular procedure competency, clinical practice, career, and lifestyle with the aim of attracting trainees to the field of VS. The author's operative logs were reviewed retrospectively to summarize vascular procedures performed before and after the vascular fellowship. Statistical analysis was performed comparing the types and volume of vascular procedures before and after the vascular fellowship. Changes in professional career and personal life also were examined. The author performed 401 vascular procedures during 2.8 years as a general surgeon. In the first 3.4 years after the vascular fellowship, vascular procedure volume increased to 1563. The mean number of vascular procedures performed per year increased from 143.2 as a general surgeon to 459.7 as a vascular surgeon. The three major differences in vascular procedures occurring after the vascular fellowship were (1) a threefold increase in the number of vascular procedures performed, (2) a shift from major open to venous and endovascular procedures, and (3) an increase in case complexity. Specializing in VS also has resulted in increased career opportunities, more career satisfaction, a direct financial benefit, and more flexibility for lifestyle and family. Because of these positive changes, the author encourages medical students and residents interested in VS to explore the specialty early, seek vascular surgeons to serve as mentors, and enter one of the new VS

  5. Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

    Energy Technology Data Exchange (ETDEWEB)

    Briquez, Priscilla S.; Hubbell, Jeffrey A.; Martino, Mikaël M.


    Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.

  6. New methodologies for patients rehabilitation. (United States)

    Fardoun, H M; Mashat, A S; Lange, B


    The present editorial is part of the focus theme of Methods of Information in Medicine titled "New Methodologies for Patients Rehabilitation", with a specific focus on technologies and human factors related to the use of Information and Communication Technologies (ICT) for improving patient rehabilitation. The focus theme explores different dimensions of empowerment methodologies for disabled people in terms of rehabilitation and health care, and to explores the extent to which ICT is a useful tool in this process. The focus theme lists a set of research papers that present different ways of using ICT to develop advanced systems that help disabled people in their rehabilitation process.

  7. Induction, complexity, and economic methodology


    Smith, Peter


    This paper focuses on induction, because the supposed weaknesses of that process are the main reason for favouring falsificationism, which plays an important part in scientific methodology generally; the paper is part of a wider study of economic methodology. The standard objections to, and paradoxes of, induction are reviewed, and this leads to the conclusion that the supposed ‘problem’ or ‘riddle’ of induction is a false one. It is an artefact of two assumptions: that the classic two-valued...

  8. Acoustic emission methodology and application

    CERN Document Server

    Nazarchuk, Zinoviy; Serhiyenko, Oleh


    This monograph analyses in detail the physical aspects of the elastic waves radiation during deformation or fracture of materials. I presents the  methodological bases for the practical use of acoustic emission device, and describes the results of theoretical and experimental researches of evaluation of the crack growth resistance of materials, selection of the useful AE signals. The efficiency of this methodology is shown through the diagnostics of various-purpose industrial objects. The authors obtain results of experimental researches with the help of the new methods and facilities.

  9. Observational methodology in sport sciences

    Directory of Open Access Journals (Sweden)

    M. Teresa Anguera


    Full Text Available This paper reviews the conceptual framework, the key literature and the methods (observation tools, such as category systems and field formats, and coding software, etc. that should be followed when conducting research from the perspective of observational methodology. The observational designs used by the authors’ research group over the last twenty years are discussed, and the procedures for analysing data and assessing their quality are described. Mention is also made of the latest methodological trends in this field, such as the use of mixed methods.

  10. Qualitative Methodology in Unfamiliar Cultures

    DEFF Research Database (Denmark)

    Svensson, Christian Franklin


    This case study discusses qualitative fieldwork in Malaysia. The trends in higher education led to investigating how and why young Indians and Chinese in Malaysia are using the university to pursue a life strategy. Given the importance of field context in designing and analysing research based...... on a qualitative methodology, conscious reflection on research design and objectivity is important when doing fieldwork. This case study discusses such reflections. Emphasis throughout is given to applied qualitative methodology and its contributions to the social sciences, in particular having to do...

  11. Methodological Guidelines for Advertising Research

    DEFF Research Database (Denmark)

    Rossiter, John R.; Percy, Larry


    In this article, highly experienced advertising academics and advertising research consultants John R. Rossiter and Larry Percy present and discuss what they believe to be the seven most important methodological guidelines that need to be implemented to improve the practice of advertising research....... Their focus is on methodology, defined as first choosing a suitable theoretical framework to guide the research study and then identifying the advertising responses that need to be studied. Measurement of those responses is covered elsewhere in this special issue in the article by Bergkvist and Langner. Most...

  12. Maternal homocystinuria and Moebius syndrome? Vascular aetiology


    Gupta, N.; Anthony, M Y


    A case of Moebius syndrome is reported in an infant of a mother known to have pyridoxine-unresponsive homocystinuria. The authors suggest that Moebius syndrome could result from early vascular insufficiency or disruption occurring early in development related to maternal homocystinuria.

  13. Membrane-mediated regulation of vascular identity. (United States)

    Hashimoto, Takuya; Tsuneki, Masayuki; Foster, Trenton R; Santana, Jeans M; Bai, Hualong; Wang, Mo; Hu, Haidi; Hanisch, Jesse J; Dardik, Alan


    Vascular diseases span diverse pathology, but frequently arise from aberrant signaling attributed to specific membrane-associated molecules, particularly the Eph-ephrin family. Originally recognized as markers of embryonic vessel identity, Eph receptors and their membrane-associated ligands, ephrins, are now known to have a range of vital functions in vascular physiology. Interactions of Ephs with ephrins at cell-to-cell interfaces promote a variety of cellular responses such as repulsion, adhesion, attraction, and migration, and frequently occur during organ development, including vessel formation. Elaborate coordination of Eph- and ephrin-related signaling among different cell populations is required for proper formation of the embryonic vessel network. There is growing evidence supporting the idea that Eph and ephrin proteins also have postnatal interactions with a number of other membrane-associated signal transduction pathways, coordinating translation of environmental signals into cells. This article provides an overview of membrane-bound signaling mechanisms that define vascular identity in both the embryo and the adult, focusing on Eph- and ephrin-related signaling. We also discuss the role and clinical significance of this signaling system in normal organ development, neoplasms, and vascular pathologies. © 2016 Wiley Periodicals, Inc.

  14. Vascular factors in dementia and apathy

    NARCIS (Netherlands)

    Eurelings, L.S.M.


    The number of individuals suffering from dementia is expected to rise significantly in the future. Because so far no curative treatment exists, prevention remains paramount. A large body of evidence points to the direction of an important role of vascular risk factors in the aetiology of dementia

  15. Self-management of vascular risk factors

    NARCIS (Netherlands)

    Sol-de Rijk, B.G.M.


    Summary The aim of this thesis was to provide insight into the potential of a self-management approach in treatment of vascular risk factors and to develop a self-management intervention. Furthermore to examine if this intervention, based on self-efficacy promoting theory, is effective in reducing

  16. Angiogenesis: the genetic regulation of vascular development

    NARCIS (Netherlands)

    R.A. Haasdijk (Remco Anton)


    markdownabstract__Abstract__ For centuries, many scientists are fascinated by the organisation of the vascular network. The Greek philosopher and polymath Aristotle (384 BC) was one of the first man who described the vasculature. He wrote: “the system of blood vessels in the body may

  17. Vascular risk factors, cognitve decline, and dementia

    Directory of Open Access Journals (Sweden)

    E Duron


    Full Text Available E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

  18. Dynamics of nephron-vascular network

    DEFF Research Database (Denmark)

    Postnov, Dmitry; Postnov, D E; Marsh, D J


    to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode...

  19. Cerebral dysplastic vascular malformation: a developmental arrest

    Energy Technology Data Exchange (ETDEWEB)

    Wortzman, G.; Sima, A.A.F.; Morley, T.P.


    A cryptic malformation of the brain was found to represent an arrest in vascular development. Microscopy showed plump endothelium of blood vessels, which did not have a normal lumen and consisted of solid cords of cells. The microscopic, angiographic, and computed tomographic appearance of this anomaly are discussed and compared with cavernous angiomas, arteriovenous malformations, and venous angiomas.

  20. Biodegradable Microfluidic Scaffolds for Vascular Tissue Engineering (United States)


    bonding multiple microfluidic layers. Introduction Overcoming the problems of nutrient transport is critical in the design of tissue intrinsic vascular network within these scaffolds. More specifically, the application of microfabrication and BioMEMS technology has been focused