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Sökning: WFRF:(Witkowski A)

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  • Fuchs, A., et al. (författare)
  • Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
  • 2018
  • Ingår i: Frontiers in Immunology. - 1664-3224. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.
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  • Maffi, P., et al. (författare)
  • Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes
  • 2020
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:4, s. 710-718
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study () was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 +/- 5 after the first and day 365 +/- 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.
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  • Warsame, Marian, et al. (författare)
  • High therapeutic efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Somalia
  • 2019
  • Ingår i: Malaria Journal. - 1475-2875. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller (Pfk13) domain and amplification in Pfplasmepsin 2 (Pfpm2) gene in Somalia. Methods: One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia. Results: A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA-PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13, only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results. Conclusions: AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia.
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  • Sawicki, M., et al. (författare)
  • Homogeneous and heterogeneous magnetism in (Zn,Co)O : From a random antiferromagnet to a dipolar superferromagnet by changing the growth temperature
  • 2013
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 88:8
  • Tidskriftsartikel (refereegranskat)abstract
    • A series of (Zn,Co)O layers with Co contents x up to 40% grown by atomic layer deposition have been investigated. All structures deposited at 160 degrees C show magnetic properties specific to II-VI dilute magnetic semiconductors with localized spins S = 3/2 coupled by strong but short-range antiferromagnetic interactions resulting in low-temperature spin-glass freezing for x = 0.16 and 0.4. At higher growth temperature (200 degrees C) metallic Co nanocrystals precipitate in two locations giving rise to two different magnetic responses: (i) a superparamagnetic contribution coming from volume disperse nanocrystals; (ii) a ferromagneticlike behavior brought about by nanocrystals residing at the (Zn,Co)O/substrate interface. It is shown that the dipolar coupling within the interfacial two-dimensional dense dispersion of nanocrystals is responsible for the ferromagneticlike behavior.
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