| 1. |
- Graae, Anne-Sofie, et al.
(författare)
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ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:3, s. 502-514
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Tidskriftsartikel (refereegranskat)abstract
- The ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity. We show that the variant is associated with increased expression of the secreted ADAMTS9 and decreased insulin sensitivity and signaling in human skeletal muscle. In line with this, mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity. The molecular link between ADAMTS9 and insulin signaling was characterized further in a model where ADAMTS9 was overexpressed in skeletal muscle. This selective over expression resulted in decreased insulin signaling presumably mediated through alterations of the integrin 131 signaling pathway and disruption of the intracellular cytoskeletal organization. Furthermore, this led to impaired mitochondria! function in mouse muscle-an observation found to be of translational character because humans carrying the ADAMTS9 risk allele have decreased expression of mitochondrial markers. Finally, we found that the link between ADAMTS9 overexpression and impaired insulin signaling could be due to accumulation of harmful lipid intermediates. Our findings contribute to the understanding of the molecular mechanisms underlying insulin resistance and type 2 diabetes and point to inhibition of ADAMTS9 as a potential novel mode of treating insulin resistance.
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| 2. |
- Johansen, Jeanne D., et al.
(författare)
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European Society of Contact Dermatitis guideline for diagnostic patch testing : recommendations on best practice
- 2015
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 73:4, s. 195-221
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Forskningsöversikt (refereegranskat)abstract
- The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
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| 3. |
- Suihko, Christian, 1956-, et al.
(författare)
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Fluorescent fibre-optic confocal characterization of in vivo epidermal changes in atopic eczema
- 2020
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Ingår i: Skin research and technology. - : WILEY. - 0909-752X .- 1600-0846. ; 26:4, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- Background/aims Fibre-optic confocal imaging (FOCI) allows non-invasive visualization of live skin in vivo. A contrast agent, a fluorophore, is injected into the dermis. FOCI images are horizontal optical sections with cellular resolution. The aim was to study in vivo epidermal changes and the cellular structure of keratinocytes in moderate to severe atopic eczema (AE). Methods Eight patients with AE with active lesions on the forearms were studied and compared to a control group of six healthy individuals, and two cases of AE without activity. Fluorescein sodium was used as fluorophore. A hand-held fibre-optic laser scanner (Stratum (R)) was used. The study included morphometric analyses. Results The confocal in vivo images identified characteristic features of epidermis and keratinocytes in active AE vs healthy skin controls. FOCI could non-invasively image acanthosis, spongiosis, and parakeratosis in AE. Epidermal oedema and micro-vesicles were visualized. Morphometry based on FOCI demonstrated 14% increased width of keratinocytes of atopic skin vs healthy controls. The epidermal structures and organization in distinctive cell layers were deviant as a result of the disease. Conclusions Fibre-optic confocal imaging can visualize essential epidermal structures of atopic eczema directly in vivo, in real-time, and with cellular resolution thus without disturbing the natural state of the skin. FOCI is primarily a research tool, but with a potential to become used in the clinic for non-invasive microscopic diagnosis of AE and monitoring of effect of therapies.
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| 4. |
- Suihko, Christian, et al.
(författare)
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Fluorescent fibre-optic confocal imaging of lesional and non-lesional psoriatic skin compared with normal skin in vivo
- 2012
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Ingår i: Skin research and technology. - : John Wiley and Sons. - 0909-752X .- 1600-0846. ; 18:4, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- Background/aims Fibre-optic confocal imaging (FOCI) allows non-invasive visualization of live skin in vivo. A contrast agent, a fluorophore, is injected in the dermis. FOCI images are optical sections from a horizontal (en face) view. The aim was to study epidermis and the cellular structure of keratinocytes of psoriatic plaques and adjacent non-lesional with healthy skin as a reference. Methods Twelve patients with stable plaque psoriasis were studied and compared with a control group of eight healthy individuals. Fluorescein sodium was used as fluorophore. A hand held fibre-optic laser scanner (Stratum (R); Optiscan Pty., Melbourne, Australia) was used. The study included morphometric analyses. Results The confocal in vivo images demonstrated characteristic features of epidermis and keratinocytes in lesional and non-lesional skin vs. healthy skin. Morphometry based on FOCI demonstrated an approximately 30% increased width of keratinocytes of psoriatic skin vs. healthy control, and the number of keratinocytes per viewing field was reduced. FOCI allowed non-invasive visualization of cell nuclei and parakeratosis of psoriatic epidermis. The horizontal width of dermal papillae of psoriatic skin was increased by approximately 50% as compared with healthy skin, and the flow of erythrocytes in the papillar vessels could be observed in real-time. Conclusion FOCI can directly visualize essential epidermal structures of plaque psoriasis in vivo, in real-time and with cellular resolution without the need of taking biopsies and thus without disturbing the natural state of the skin. FOCI is a versatile future tool for non-invasive microscopic diagnosis and therapy follow-up of psoriasis.
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