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Sökning: AMNE:(MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper) > Luleå tekniska universitet

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1.
  • Ponsot, Elodie, 1973-, et al. (författare)
  • Skeletal muscle telomere length is not impaired in healthy physically active old women and men
  • 2008
  • Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 37:4, s. 467-472
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that the number of satellite cells is lower in old than young men and women. The aim of this study was to further explore the effects of aging on the regenerative potential of skeletal muscle in 16 young and 26 old men and women with comparable physical activity level (young, 25 +/- 4 years; old, 75 +/- 4 years). Mean and minimum telomere lengths were determined using Southern blot analyses on biopsies obtained from the tibialis anterior muscle. There were no significant age or gender effects on mean and minimal telomeric lengths, suggesting that the replicative potential in the remaining satellite cells in the tibialis anterior muscle is not impaired with increasing age and the existence of in vivo regulatory mechanisms allowing the maintenance of telomere length. These results imply that moderate physical activity regularly performed by old subjects is not associated with accelerated telomere loss.
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2.
  • Shahim, Pashtun, 1984, et al. (författare)
  • Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
  • 2016
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:11, s. 1308-1315
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance:Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.Objective:To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.Design, Settings, and Participants:A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.Main Outcomes and Measures:Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.Results:A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05).Conclusions and Relevance:Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.
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3.
  • Rönmark, Eva, et al. (författare)
  • High incidence and persistence of airborne allergen sensitization up to age 19 years
  • 2017
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 72:5, s. 723-730
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.METHODS: All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations.RESULTS: Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.CONCLUSION: The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance.
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4.
  • Alrifaiy, Ahmed, et al. (författare)
  • A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy : first investigations of single biological cells
  • 2015
  • Ingår i: Biomedical engineering online. - : Springer Science and Business Media LLC. - 1475-925X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.
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5.
  • Morales, Javier O., et al. (författare)
  • A design of experiments to optimize a new manufacturing process for high activity protein-containing submicron particles
  • 2013
  • Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 39:11, s. 1793-1801
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel method for the manufacture of protein/peptide-containing submicron particles was developed in an attempt to provide particles with increased activity while using high energy input technologies. The method consists of antisolvent co-precipitation from an aqueous solution containing both an amino acid core material (e.g. D,L-valine), and either bovine serum albumin (BSA) or lysozyme (Lys) as model proteins. The aqueous solution was added to the organic phase by means of a nebulizer to increase the total surface area of interaction for the precipitation process. Sonication proved to be an effective method to produce small particle sizes while maintaining high activity of Lys. The use of a polysorbate or sorbitan ester derivatives as stabilizers proved to be necessary to yield submicron particles. Particles with very high yields (approximately 100%) and very high activity after manufacture (approximately 100%) could be obtained. A particle size of 439.0 nm, with a yield of 48.8% and with final remaining activity of 98.7% was obtained. By studying various factors using a design of experiments strategy (DoE) we were able to establish the critical controlling factors for this new method of manufacture.
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6.
  • Morales, Javier O., et al. (författare)
  • Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery
  • 2014
  • Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 122, s. 38-45
  • Tidskriftsartikel (refereegranskat)abstract
    • The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin.
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7.
  • Morales, Javier O., et al. (författare)
  • Lipid nanoparticles for the topical delivery of retinoids and derivatives
  • 2015
  • Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 10:2, s. 253-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed.
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8.
  • Morales, Javier O., et al. (författare)
  • Manufacture and characterization of mucoadhesive buccal films
  • 2011
  • Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 77:2, s. 187-199
  • Tidskriftsartikel (refereegranskat)abstract
    • The buccal route of administration has a number of advantages including bypassing the gastrointestinal tract and the hepatic first pass effect. Mucoadhesive films are retentive dosage forms and release drug directly into a biological substrate. Furthermore, films have improved patient compliance due to their small size and reduced thickness, compared for example to lozenges and tablets. The development of mucoadhesive buccal films has increased dramatically over the past decade because it is a promising delivery alternative to various therapeutic classes including peptides, vaccines, and nanoparticles. The "film casting process" involves casting of aqueous solutions and/or organic solvents to yield films suitable for this administration route. Over the last decade, hot-melt extrusion has been explored as an alternative manufacturing process and has yielded promising results. Characterization of critical properties such as the mucoadhesive strength, drug content uniformity, and permeation rate represent the major research areas in the design of buccal films. This review will consider the literature that describes the manufacture and characterization of mucoadhesive buccal films.
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9.
  • Morales, Javier O., et al. (författare)
  • Novel Nanostructured Polymeric Carriers to Enable Drug Delivery for Cardiovascular Diseases
  • 2015
  • Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 21:29, s. 4276-4284
  • Tidskriftsartikel (refereegranskat)abstract
    • Applications of polymeric nanotechnologies for enabling therapies for cardiovascular diseases have shown recent success. Both intravenous and oral administration have been investigated and achieved different degrees of development. While circulating polymeric nanostructured carriers are subjected to a number of interactions, smart nanoparticle design has enabled the formulation of active molecules to be delivered to specific targets for cardiovascular effects. This review aims at outlining the multiple factors that can affect the fate of polymeric nanostructured carriers in systemic circulation. With an understanding of these factors, the literature on the various polymeric nanostructured carriers is reviewed. Finally, the emerging uses of nanotechnology to formulate orally administered drugs for cardiovascular diseases are depicted.
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10.
  • Morales, Javier O., et al. (författare)
  • Novel strategies for the buccal delivery of macromolecules
  • 2014
  • Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 40:5, s. 579-590
  • Tidskriftsartikel (refereegranskat)abstract
    • For years now, the delivery of small molecules through the buccal mucosal route has been described in the literature, but it has only been over the past decade that investigations into macromolecule delivery via the buccal route have sharply increased. The administration of macromolecules such as proteins and peptides, antibodies, or nucleic acids by buccal administration would be greatly enhanced due to the avoidance of the gastrointestinal conditions, rapid uptake into systemic circulation, as well as the potential for controlled drug delivery. Since macromolecules are faced with a number of specific challenges related to permeation through the epithelium, several strategies have been employed historically to improve their buccal absorption and subsequent bioavailability. Several conventional strategies to improve macromolecule penetration include the use of chemical permeation enhancers, enzyme inhibitors and the use of mucoadhesive materials acting as carriers. More recent approaches include the incorporation of the macromolecule as part of nanostructured delivery systems to further enhance targeting and delivery. This review focuses on the different permeation enhancing strategies as well as formulation design that are tailored to meet the challenges of active macromolecule delivery using the buccal mucosal route of administration.
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