314 research outputs found
Electrospinning of Bioactive Dex-PAA Hydrogel Fibers
No full textabstract: In this work, a novel method is developed for making nano- and micro- fibrous hydrogels capable of preventing the rejection of implanted materials. This is achieved by either (1) mimicking the native cellular environment, to exert fine control over the cellular response or (2) acting as a protective barrier, to camouflage the foreign nature of a material and evade recognition by the immune system. Comprehensive characterization and in vitro studies described here provide a foundation for developing substrates for use in clinical applications. Hydrogel dextran and poly(acrylic acid) (PAA) fibers are formed via electrospinning, in sizes ranging from nanometers to microns in diameter. While "as-electrospun" fibers are continuous in length, sonication is used to fragment fibers into short fiber "bristles" and generate nano- and micro- fibrous surface coatings over a wide range of topographies. Dex-PAA fibrous surfaces are chemically modified, and then optimized and characterized for non-fouling and ECM-mimetic properties. The non-fouling nature of fibers is verified, and cell culture studies show differential responses dependent upon chemical, topographical and mechanical properties. Dex-PAA fibers are advantageously unique in that (1) a fine degree of control is possible over three significant parameters critical for modifying cellular response: topography, chemistry and mechanical properties, over a range emulating that of native cellular environments, (2) the innate nature of the material is non-fouling, providing an inert background for adding back specific bioactive functionality, and (3) the fibers can be applied as a surface coating or comprise the scaffold itself. This is the first reported work of dex-PAA hydrogel fibers formed via electrospinning and thermal cross-linking, and unique to this method, no toxic solvents or cross-linking agents are needed to create hydrogels or for surface attachment. This is also the first reported work of using sonication to fragment electrospun hydrogel fibers, and in which surface coatings were made via simple electrostatic interaction and dehydration. These versatile features enable fibrous surface coatings to be applied to virtually any material. Results of this research broadly impact the design of biomaterials which contact cells in the body by directing the consequent cell-material interaction.Dissertation/ThesisPh.D. Bioengineering 201
Improving the blood clearance time of I-125 labeled Dex-g-PMAGGCONHTyr by copolymerization
No full textDextran graft copolymers, including dextran graft poly(N-methacryloylglycylglycine) copolymers conjugated with polyethylene glycol and tyrosine (Dex-g-PMAGGCONHPEG(3k)-NHTyr), dextran graft poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(HPMA-co-MAGGCONHTyr)), and dextran graft poly(methacrylpolyethylene glycol-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(MPEG-co-MAGGCONHTyr)) were synthesized for the purpose to improve the biodistribution and blood clearance time of ploy(N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-PMAGGCONHTyr). Dynamic light scattering (DLS) results indicated that no aggregation formed in 0.9% saline solution. The graft copolymers were labeled with I-125 and the labeled copolymers are stable in 0.9% saline and 1% BSA of PBS solutions. Pharmacokinetics studies showed that I-125 labeled graft copolymer Dex-g-P(HPMA-co-MAGGCONHTyr) had a longer blood clearance time than the others. Biodistribution images confirmed the preferable liver and spleen accumulation at 1 h after injection, and especially for blood tissue, the mean %ID/g value of the PHPMA-modified graft copolymer Dex-g-P(HPMA-co-MAGGCONHTyr) is 7 folds higher than that of Dex-g-PMAGGCONHTyr.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000292965500036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Polymer ScienceSCI(E)EI6ARTICLE81872-1878
Effects of dexamethasone on host innate and adaptive immune responses and parasite development in rainbow trout Oncorhynchus mykiss infected with Loma salmonae
No full textThe effects of dexamethasone (dex) treatment on infections with the microsporidian parasite, Loma salmonae and the effects of dex on initiation of the adaptive immune response were investigated in rainbow trout, Oncorhynchus mykiss experimentally infected with the parasite. Dex treatment resulted in significantly higher infections with the parasite in the gills and other internal organs, suggesting that dex inhibits aspects of the innate immune response to L. salmonae; the heavier infections in the gills and organs of rainbow trout resembled infections seen in Chinook salmon. Mean xenoma counts per microscope field in the gills of fish infected with L. salmonae treated with dex or left untreated were 169 and 30, respectively. Although higher numbers of xenomas were observed in dex treated fish, the xenomas were generally smaller in size than in infected control fish. The xenomas in dex treated fish showed morphological signs of degeneration including loss and degeneration of early parasite stages, accumulation of amorphous material in xenomas, and infiltration with phagocytic cells containing degenerated parasites. The xenomas in infected untreated fish had larger xenomas with a more uniform size and contained identifiable parasite stages in the cytoplasm. According to this study, once fish have developed an adaptive immune response to the parasite by previous exposure, then fish have 100% protection to reinfection even when treated with heavy doses of dex. L. salmonae immune fish treated or untreated with dex during reinfection with the parasite developed no xenomas in the gills 6 weeks post reinfection. These results indicate that once the cellular response is primed to L. salmonae, then dex related immunosuppression does not reduce the effectiveness of the adaptive immune response
The Healthiest Mall In The Netherlands: Revitalising the Palace Promenade in Scheveningen
No full textPalace PromenadeArchitecture, Urbanism and Building Sciences | Heritage & Architectur
Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival
No full textWe evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death. © 2018, The Author(s)
The ARRIVE guidelines 2.0: Author checklist.
No full textClinically useful anesthetics are associated with delirium and cognitive decline in the elderly. Dexmedetomidine (Dex), an α2 adrenergic receptor agonist, is an intravenous sedative with analgesic properties. Dex is associated with a lower incidence of delirium in the elderly. In this study, we first assessed whether a high dose of Dex alone was a clinically useful anesthetic. Finding that it was not, we sought to determine whether supplementation of Dex with low doses of two common anesthetics, propofol or sevoflurane, created an effective general anesthetic. Rats were sedated with a bolus followed by a continuous infusion of Dex and a low dose of a second agent—propofol, or sevoflurane. A strong noxious stimulus was applied every 15 minutes while monitoring vital signs. A combination of the α2 competitive antagonist, atipamezole, and caffeine was administered to reverse the anesthesia. Abdominal surgery was used to validate the efficacy of these dosing regimens. The animals responded to noxious stimuli when receiving Dex alone. Supplementing Dex with either a low dose of propofol or sevoflurane completely suppressed responses to the noxious stimulus and allowed the rats to tolerate abdominal surgery with complete immobility and no alterations in vital signs, suggesting that the drug combinations were effective anesthetics. EEG recordings showed suppression of high frequency activity suggesting that awareness and memory were impaired. Previously we found that combination of atipamezole and caffeine rapidly and completely reversed the sedation and bradycardia elicited by Dex. In this study, atipamezole and caffeine accelerated the time to emergence from unconsciousness by >95% in Dex supplemented with either propofol or sevoflurane.In conclusionOur results suggest that Dex supplemented with a low dose of a second agent creates a potent anesthetic that is rapidly reversed by atipamezole and caffeine.</div
De ontwikkeling van de bollenschuur: tussen 1850 en 1965
No full textDe bloembollencultuur speelt al anderhalve eeuw een belangrijke rol in het landschap van de Bollenstreek. Zo heeft deze bloembollencultuur van 1850 tot 1965 ook in gebouwde erfgoed haar sporen nagelaten. Na 1965 is de herkenbare bloembollenschuur haar karakteristieke eigenschappen verloren en zijn ze nog moeilijk te onderscheiden van andere bedrijfshallen. De afgelopen jaren is er dan ook steeds meer aandacht gekomen voor de bollenschuren tot 1965. Zo’n 25 jaar geleden werden de bollenschuren al van cultuurhistorisch belang gezien. Vanuit gemeentes in de Bollenstreek wordt daarom ook gesproken over het behouden en herbestemmen van de (monumentale) bollenschuren. Zo wordt er elk jaar door de Werkgroep Behoud en Herbestemming Bollenerfgoed van het Cultuurhistorisch Genootschap Duin- en Bollenstreek de Zwarte Tulp-prijs uitgereikt. Deze is bedoeld bestemd voor de eigenaar van een bollenschuur in de Bollenstreek die hun bollenschuur op een goede manier hebben behouden of herbestemd.Het doel van deze thesis is om de ontwikkeling van de bloembollenschuren vanaf 1850 tot 1965 in kaart te brengen. Het is hierbij van belang de redenen van deze ontwikkelingen hierbij vast te leggen en te kijken hoe dit van invloed is geweest. Hierbij luidt mijn hoofdvraag ‘‘Hoe zijn de bollenschuren in de Bollenstreek veranderd tussen de jaren 1850 en 1965 en waarom?’’Hierbij wordt gekeken naar verschillende nog bestaande bollenschuren uit deze periode. Zowel het exterieur als het interieur tussen de verschillende type bollenschuren worden met elkaar vergeleken en bij verschillen wordt er gezocht naar de reden waarom een verandering heeft plaatsgevonden. Dit zal gedaan worden met bestaande literatuur en het bezoeken van verschillende bollenschuren.Uit het onderzoek is gebleken dat de grootste reden waarom er verschil zit tussen de types bollenschuren komt doordat de vraag naar bloembollen vanuit Nederland vanaf de jaren 1850 zo erg is toegenomen dat de kweker de beste conditie om de bloembol te drogen en te bewaren ook daadwerkelijk kon realiseren. Hier is een periode aan experimenteren geweest over hoe dit het beste gedaan kon worden. Uiteindelijk heeft de aanleg van elektriciteit in 1922 een grote rol in gespeeld, mechanisch ventileren werd mogelijk. Dit had effect op het exterieur van de bollenschuur, de gevel werd hierdoor meer gesloten. Daarnaast veranderde ook het belang van een bollenschuur, deze is getransformeerd van een opslag naar het uithangbord van het bedrijf.AR2A011Architecture, Urbanism and Building Science
Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats
No full textThe aim of this study was to evaluate the effect of dexmedetomidine (DEX) on hippocampal synaptic activity in vivo. The adult rats used for this study received a intraperitoneal bolus injection of 3, 10, 30, or 100 mu g/kg of DEX or an equivalent volume of saline. Electrophysiological recording of the hippocampal CA1 region was initiated 20 min after drug administration. The results are expressed as the percentages of the population spike amplitude measured just before high-frequency stimulation (HFS). The electrophysiological data were analyzed with an area under the curve (AUC) of 10-60 min after HFS. Moreover, to investigate the sedative dose of DEX in rats, we recorded the duration of loss of spontaneous movement after the administration of each dose of DEX. Intraperitoneal administration of DEX at doses of 30 and 100 mu g/kg induced a range of sedative effects. The AUC measurements were significantly lower in the 30 and 100 mu g/kg groups than in those injected with vehicle (vehicle: 8.81 +/- A 0.49, n = 7; DEX 30 A mu g/kg: 6.02 +/- A 0.99, n = 6; DEX 100 A mu g/kg: 5.10 +/- A 0.43, n = 5; P < 0.05). The results of our in vivo study reveal that sedative doses of DEX impaired the induction of hippocampal long-term potentiation (LTP). These findings may signify a causal link between DEX-induced sedative action and hippocampal LTP suppression, providing a better understanding of the mechanisms underlying the DEX-induced sedative and/or amnestic effect
Preparation of a poly(acrylic acid) based hydrogel with fast adsorption rate and high adsorption capacity for the removal of cationic dyes
No full textA biocompatible Dex-MA/PAA hydrogel was prepared through copolymerization of glycidyl methacrylate substituted dextran (Dex-MA) with acrylic acid (AA), which was applied as the adsorbent to remove cationic dyes from aqueous solutions. Dex-MA/PAA hydrogel presented a fast adsorption rate and the removal efficiency of Methylene Blue (MB) and Crystal Violet (CV) reached 93.9% and 86.4%, respectively within one minute at an initial concentration of 50 mg L-1. The adsorption equilibrium data fitted the Sips isotherm model well with high adsorption capacities of 1994 mg g-1 for MB and 2390 mg g-1 for CV. Besides, dye adsorption occurred efficiently over the pH range 3-10 and the temperature range 20-60 °C. Moreover, the removal efficiencies for MB and CV were still >95% even after five adsorption/desorption cycles which indicates the robust nature of the Dex-MA/PAA hydrogel and its potential as an eco-friendly adsorbent for water treatment.ChemE/Advanced Soft Matte
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