340 research outputs found
A fresh perspective into the study of refugee wellbeing
In collaboration with Karl-Andrew Woltin from Roehampton University and Kai Sassenberg from the University of Tübingen, PhD candidate Nihan Albayrak has published a new study in PLoS ONE, which offers a new approach to studying and supporting refugees
Effects of Rho-kinase inhibition in chronic experimental pulmonary hypertension
Pulmonary hypertension (PH) is a severe chronic and life-threatening disease characterized by progressive augmentation of pulmonary arterial pressure that finally leads to right ventricle failure and death. PH has a multi-complex pathology which includes a combination of pulmonary vascular remodelling, vasoconstriction and in situ thrombosis. Key to the severity of the disease is the progressive pulmonary vascular remodelling. The progressive pulmonary vascular remodelling is the attribute of PH pathology and is characterized by abnormalities of vascular cells such as increased proliferation, migration and resistance to apoptosis. Although the PH pathology is the subject of intensive research the precise molecular mechanisms are still not fully understood and successful therapeutic strategy to cure the disease is still needed.
An accumulating body of evidence incriminates Rho-kinase (ROCK) in the pathogenesis of PH and suggests the Rho-kinase as a promising therapeutic target. In the line with literature, our study aimed to investigate the therapeutic effects of a novel highly selective and orally active ROCK inhibitor, azaindole-1 in animal models of PH. We successfully demonstrated that azaindole-1 significantly inhibited hypoxic pulmonary vasoconstriction in isolated, ventilated and buffer-perfused murine lungs and proliferation of primary rat pulmonary artery smooth muscle cells in vitro. Furthermore, azaindole-1 chronic treatment improved hemodynamics and right ventricular hypertrophy in both experimental models of PH. Moreover, the medial wall thickness and muscularization of peripheral pulmonary arteries, as measures of pulmonary vascular remodelling, were significantly ameliorated. Finally, azaindole-1 treatment resulted in a decreased immunoreactivity for phospho-myosin phosphatase target subunit-1 (p-MYPT-1) and proliferating cell nuclear antigen (PCNA) in pulmonary vessels of monocrotaline-injected rats, suggesting an impaired ROCK activity and reduced proliferating vascular cells.
In conclusion, azaindole-1 provided therapeutic benefit in experimental PH and this may be attributable to its potent vasorelaxant and antiproliferative effects. Thus, azaindole-1 may offer a useful approach for the treatment of pulmonary hypertension and may have a potential clinical application.Pulmonaler Hochdruck (PH) ist eine schwere chronische und lebensbedrohliche Erkrankung, charakterisiert duch progressive Zunahme des pulmonal arteriellen Drucks, welche letztlich in Rechtsherzversagen und Tod endet. PH hat besitzt eine komplexe Pathologie mit der Kombination eines Remodelling der Pulmonalgefäße, Vasokonstriktion und in situ Thrombose. Der Schlüssel zu der Schwere dieser Erkrankung ist das progressiv verlaufende Gefäßremodelling. Dieses progressive pulmonale Gefässremodelling ist das Attribut der PH Pathologie und wird charakterisiert durch Abnormalitäten der Gefäßzellen, wie zB. Verstärkte Proliferation, Migration, und Unempfindlichkeit gegenüber Apoptose. Obwohl die PH Pathologie Gegenstand intensiver Forschung ist, sind die genauen molekularen Mechanismen noch nicht vollständig verstanden. Eine erfolgreiche Therapie zur Heilung dieser schweren Krankheit ist noch nicht verfügbar. Rho-kinasen (ROCK) scheinen in der Pathologie der PH eine wichtige Rolle zu spielen und lassen vermuten, hier einen erfolgsversprechenden Angriffspunkt für eine mögliche Therapie darzustellen.
Im Einklang mit dementsprechender Literatur, erforschen unsere Studien im Tiermodell den therapeutischen Effekt des hochselektiven, oral verfügbaren ROCK Inhibitors, Azaindole-1. Wir konnten erfolgreich zeigen, dass Azaindole-1 die Vasokonstriktion in isolierter, ventilierter und Puffer-perfundierter Mauslunge sowie die Proliferation von arteriellen glatten Muskelzellen der Ratte in vitro verminderte. Weiterhin verbesserte eine Behandlung mit Azaindole-1 die Hämodynamik und Rechtsherzhypertrophie in zwei Tiermodellen der PH. Ebenfalls kam es zu einer signifikanten Verbesserung der medialen Wandstärke sowie dem Muskularisierungsgrad der Pulmonalgefäße, welche als Paramater für das vaskuläre Remodelling gelten. Letztlich führte eine Behandlung mit Azaindole-1 zu einer Abnahme der Immunreaktivität der Phospho-Myosin Phosphatase Target Subunit-1 (p-MYPT-1) und PCNA (prolferating cell nuklear antigen) in Pulmonalgefäßen der mit Monocrotalin injizierten Ratten, was auf eine geminderte ROCK Aktivität und reduzierte Anzahl proliferierender Gefäßzellen schließen lässt.
Zusammenfassend lässt sich sagen, dass Azaindole-1 ein vielversprechender Ansatz für die Behandlung experimenteller PH darstellt, was sich wahrscheinlich auf seine potenten vasorelaxierenden und antiproliferierenden Effekte zurückführen lässt. Dadurch könnte Azaindole-1 einen guten Therapieansatz für die Behandlung des pulmonalen Hochdrucks darstellen und das Potential für eine klinische Anwendung besitzen
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Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function.
Background: Chronic neuropathic pain (NP) is a complex disease that results from damage or presumed damage to the somatosensory nervous system. Current treatment regimens are often ineffective. The major impediment in developing effective treatments is our limited understanding of the underlying mechanisms. Preclinical evidence suggests that glial changes are crucial for the development of NP and a recent study reported oscillatory activity differences within the ascending pain pathway at frequencies similar to that of cyclic gliotransmission in NP. Furthermore, there is evidence that glial modifying medications may be effective in treating NP. The aim of this Phase I open-label clinical trial is to determine whether glial modifying medication palmitoylethanolamide (PEA) will reduce NP and whether this is associated with reductions in oscillatory activity within the pain pathway. Methods: We investigated whether 6 weeks of PEA treatment would reduce pain and infra-slow oscillatory activity within the ascending trigeminal pathway in 22 individuals (17 females) with chronic orofacial NP. Results: PEA reduced pain in 16 (73%) of the 22 subjects, 11 subjects showed pain reduction of over 20%. Whilst both the responders and non-responders showed reductions in infra-slow oscillatory activity where orofacial nociceptor afferents terminate in the brainstem, only responders displayed reductions in the thalamus. Furthermore, functional connections between the brainstem and thalamus were altered only in responders. Conclusion: PEA is effective at relieving NP. This reduction is coupled to a reduction in resting oscillations along the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission
Perception of small farmers in Serbia regarding the use of ICT and possibilities of organic agriculture
During the last two decades there is a growing awareness of the importance of introducing organic agricultural production in Serbia due to issues of health, environmental protection and need for more sustainable agriculture. There is a need for education of small farmers on the possibilities of organic production and significance of information technologies for education, production and marketing. This paper aims to examine the perception on the possibilities of organic production and ICT use concerning their level of education. The study has included 143 farmers from Raška district, municipality Kraljevo. The statistical ANOVA analysis has been done by using the software package SPSS18 to explore an impact the education has on the perception of small farmers on the use of information technologies in education, production, and marketing of agricultural products. The results show statistically significant difference in the perception of small farmers on the usage of information technologies regarding their level of education.Publishe
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Final Technical Report
The industrial Assessment Center at the University of Massachusetts completed 83 assessments in this project period, covering all states in New England and the eastern part of New York. The combined energy consumption for these facilities was more than 750,000,000 kWh costing approximately 37,000,000. The average annual energy costs per plant were 66,500 or almost 5% of their total energy bill. We have organized and participated in sixteen seminars and presentations promoting energy efficiency practices and other DOE tools and programs. Our center developed the Chilled Water System Assessment tool that is part of DOE’s BestPractices Suite of Tools. During this period we had nineteen students in the program. Fifteen were graduate students, and four were undergraduate students. Eleven of them graduated with the Masters of Science degree in mechanical engineering and are working in the energy field, and three are currently in the program. Two undergraduate students were hired by engineering firms that perform energy efficiency services, and one continued his education and is pursuing an advanced engineering degree. We cooperate with the Manufacturing Extension Partnerships and state Energy Offices to provide energy efficiency services to their constituents. As a result of our activities, all our clients requested assessments or were referred to us by one of the state energy offices, the MEP’s or DOE. Our current and former staff members hold 16 Qualified Specialist certificates. Seven of those were awarded to our students while participating in the IAC program. Currently we have three staff members with nine QS certificates and two students with four. Three people from our staff were involved in the DOE’s Save Energy Now program during the first year of program as steam and process heating qualified specialists. We completed eleven ESAs during 2006
The role of CRP and inflammation in the pathogenesis of age-related macular degeneration
Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease invol-ving the multiple genetic and environmental factors that can result in severe visual loss. The etiology of AMD is not well understood. Many theories exist and feature mechanisms of oxidative stress, athe-rosclerotic-like changes, genetic predisposition and inflammation. The most recent clinical studies appointed to a great role of inflammation and C-reactive protein (CRP) in the pathogenesis of AMD. There is a large body of evidence indicating the association of CRP with endothelial dysfunction, oxidative stress and production of reactive oxygen species (ROS), as well as with lipid status disorder in AMD patients. According to recent studies, CRP is definitely not only the inflammatory marker but also a mediator of development of the vascular disorders in the retinal circulation. The results obtai-ned from the present studies may help our understanding the pathogenesis of the retinal vascular disease associated with high levels of CRP
All-Polystyrene 3D-Printed Electrochemical Device with Embedded Carbon Nanofiber – Graphite – Polystyrene Composite Conductor
Carbon nanofibres (CNFs) and graphite flake microparticles were added to thermoplastic polystyrene polymer with the aim of making new conductive blends suitable for 3D-printing. Various polymer/carbon blends were evaluated for suitability as printable, electroactive material. An electrically conducting polystyrene composite was developed and used with commercially available polystyrene (HIPS) to manufacture electrodes suitable for electrochemical experiments. Electrodes were produced and evaluated for cyclic voltammetry of aqueous 1,1’-ferrocenedimethanol and differential pulse voltammetry detection of aqueous Pb2+ via anodic stripping. A polystyrene/CNF/graphite (80/10/10 wt%) composite provides good conductivity and a stable electrochemical interface with well-defined active geometric surface area. The printed electrodes form a stable interface to the polystyrene shell, give good signal to background voltammetric responses, and are reusable after polishing
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