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- Costabel, Ulrich, et al.
(författare)
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Pirfenidone in Idiopathic Pulmonary Fibrosis : Expert Panel Discussion on the Management of Drug-Related Adverse Events
- 2014
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 31:4, s. 375-391
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Forskningsöversikt (refereegranskat)abstract
- Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.
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- Harb, Maher, et al.
(författare)
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Picosecond dynamics of laser-induced strain in graphite
- 2011
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 84:4
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Tidskriftsartikel (refereegranskat)abstract
- We report on the use of grazing-incidence time-resolved x-ray diffraction to investigate the evolution of strain in natural graphite excited by femtosecond-laser pulses in the fluence range of 6-35 mJ/cm(2). Strains corresponding to up to similar to 2.8% c-axis expansion were observed. We show that the experimental data is in good agreement with calculations based on the Thomsen strain model in conjunction with dynamical diffraction theory. Furthermore we find no evidence of nonthermal lattice expansion as reported in recent ultrafast electron-diffraction studies of laser-excited graphite conducted under comparable excitation conditions.
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- Henderson, Neil C., et al.
(författare)
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Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:12, s. 1617-1624
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Tidskriftsartikel (refereegranskat)abstract
- Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta(3), beta(5) or beta(6) integrins or conditional loss of beta(8) integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
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- Mueller, C., et al.
(författare)
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Nanofluidic Cells with Controlled Path length and Liquid Flow for Rapid, High-Resolution In Situ Imaging with Electrons
- 2013
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:14, s. 2339-2347
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Tidskriftsartikel (refereegranskat)abstract
- The use of electron probes for in situ imaging of solution phase systems has been a long held objective, largely driven by the prospect of atomic resolution of molecular structural dynamics relevant to chemistry and biology. Here, we present a nanofluidic sample cell with active feedback to maintain stable flow conditions for pathlengths varying from 45 nm to several 100 nm, over a useable viewing area of 50 X 50 mu m. Using this concept, we demonstrate nanometer resolution for imaging weakly scattering polymer and highly scattering nanoparticles side by side with a conventional transmission microscope. The ability to flow liquids allows control over sample content and on-the-fly sample exchange, opening up the field of high-throughput electron microscopy. The nanofluidic cell design is distinguished by straightforward, reliable, operation with external liquid specimen control for imaging in (scanning) transmission mode and holds great promise for reciprocal space imaging in femtosecond electron diffraction studies of solution phase reaction dynamics.
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