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- Almokhtar, Mokhtar, et al.
(författare)
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Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.
- 2016
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 158, s. 178-188
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D-3 is a pro-hormone, which is sequentially activated by 25- and 1 alpha-hydroxylation to form 25-hydroxyvitamin D-3 [25(OH)D-3] and 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)2D(3)], respectively. Subsequent inactivation is performed by 24-hydroxylation. These reactions are carried out by a series of CYP450 enzymes. The 25-hydroxylation involves mainly CYP2R1 and CYP27A1, whereas 1 alpha-hydroxylation and 24-hydroxylation are catalyzed by CYP27B1 and CYP24A1, respectively, and are tightly regulated to maintain adequate levels of the active vitamin D hormone, 1 alpha,25(OH)(2)D-3. Altered circulating vitamin D levels, in particular 25(OH)D-3, have been linked to several disorders of the nervous system, e.g., schizophrenia and Parkinson disease. However, little is known about the mechanisms of vitamin D actions in the neurons. In this study, we examined vitamin D metabolism and its regulation in a murine motor neuron-like hybrid cell line, NSC-34. We found that these cells express mRNAs for the four major CYP450 enzymes involved in vitamin D activation and inactivation, and vitamin D receptor (VDR) that mediates vitamin D actions. We also found high levels of CYP24A1-dependent 24,25-dihydroxyvitamin D-3 [24,25(OH)(2)D-3] production, that was inhibited by the well-known CYP enzyme inhibitor ketoconazole and by several inhibitors that are more specific for CYP24A1. Furthermore, CYP24A1 mRNA levels in NSC-34 cells were up-regulated by 1 alpha,25(OH)(2)D-3 and its synthetic analogs, EB1089 and tacalcitol. Our results suggest that NSC-34 cells could be a novel model for the studies of neuronal vitamin D metabolism and its mechanism of actions.
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- Norlin, J. M., et al.
(författare)
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Real-world outcomes in 2,646 psoriasis patients : one in five has PASI ≥ 10 and/or DLQI ≥ 10 under ongoing systemic therapy
- 2017
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Ingår i: Journal of dermatological treatment (Print). - : Informa UK Limited. - 0954-6634 .- 1471-1753. ; 28:6, s. 500-504
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although biologics introduced a new era in psoriasis care when available a decade ago, it is unclear to what extent the available systemic treatments treat patients adequately. Objective To analyse the clinical severity and quality of life of the psoriasis population in Sweden treated with systemics.Methods: Data included 2,646 patients from the Swedish Registry for Systemic Treatment of Psoriasis. Average Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and EQ-5D were reported. A subgroup of persisting moderate-to-severe psoriasis as defined by PASI≥10 and/or DLQI≥10 after >12 weeks treatment was analysed.Results: Mean (SD) PASI, DLQI, and EQ-5D were 4.12 (4.57), 4.11 (5.24) and 0.79 (0.22). Eighteen percent had persisting moderate-to-severe psoriasis (n = 472). These patients were younger, had higher BMI, had psoriasis arthritis and were smoking to a larger extent (p < 0.01) compared to lower-severity patients (n = 2174). Mean (SD) EQ-5D was also considerably lower 0.63 (0.29) vs. 0.82 (0.19) (p < 0.01).Conclusion: Almost one in every five patients had persisting moderate-to-severe psoriasis, despite ongoing systemic treatment. Both comorbidities and life style factors were associated with persisting moderate-to-severe psoriasis. The considerably lower generic quality of life in these patients demonstrates an unmet need. Subsequently, improved access to biologics and continuous drug development is needed in psoriasis.
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- Ragnarson Tennvall, Gunnel, et al.
(författare)
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Health related quality of life in patients with actinic keratosis - an observational study of patients treated in dermatology specialist care in Denmark.
- 2015
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Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Actinic keratosis (AK) is a common skin condition that may progress to non-melanoma skin cancer (NMSC). The disease may influence Health Related Quality of Life (HRQoL), but studies of HRQoL in patients with AK are limited. The purpose of the study was to analyze HRQoL in patients with different severity levels of AK treated in dermatology specialist care using generic and disease-specific HRQoL instruments and to analyze their relationship.
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