| 1. |
- Tatovic, D, et al.
(author)
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Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes
- 2022
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In: Immunotherapy Advances. - : Oxford University Press (OUP). - 2732-4303. ; 2:1
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Journal article (peer-reviewed)abstract
- Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.
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| 2. |
- Bertolini, S., et al.
(author)
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The quantum vacuum of the minimal SO(10) GUT
- 2010
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In: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 259:1, s. 012098-
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Journal article (peer-reviewed)abstract
- We reexamine the longstanding no-go excluding all potentially viable SO(10) →SU(3)c⊗ SU(2)L ⊗ U(1)Y symmetry breaking patterns within the minimal renormalizable non-supersymmetric SO(10) GUT framework featuring the 45-dimensional adjoint representation in the Higgs sector. A simple symmetry argument indicates that quantum effects do change the vacuum structure of the model dramatically. A thorough analysis of the one-loop effective potential reveals that the phenomenologically favoured symmetry breaking chains passing through the SU(4)C ⊗ SU(2)L ⊗ U(1)R or SU(3)c ⊗ SU(2)L ⊗ SU(2)R ⊗ U(1)B-L intermediate stages are, indeed, supported at the quantum level. This brings the class of minimal non-supersymmetric SO(10) GUTs back from oblivion, providing a new ground for a potentially realistic model building.
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| 3. |
- Gottsäter, A., et al.
(author)
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Proinsulin secretion during the first 3 years after diagnosis in diabetic patients with and without islet cell antibodies
- 1996
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 19:6, s. 659-662
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To evaluate proinsulin secretion in different types of NIDDM. RESEARCH DESIGN AND METHODS - Proinsulin and insulin were evaluated at diagnosis of diabetes and 3 years later (fasting and after stimulation with intravenous glucose and glucagon) in 10 NIDDM patients without islet cell antibodies (ICAs) at diagnosis (age 52 ± 4 years), 11 NIDDM patients with ICAs at diagnosis (age 50 ± 5 years), and 21 healthy control subjects (age 53 ± 4 years). RESULTS - At diagnosis, fasting proinsulin was higher in NIDDM patients without ICAs than in control subjects (39.6 ± 10.0 vs. 12.8 ± 1.6 pmol/l, P < 0.01). Proinsulin response to intravenous glucose decreased in NIDDM patients with ICAs (from 35.6 ± 6.2 to 13.5 ± 5.4 pmol/l, P < 0.05), but remained unchanged in those without ICAs. At 3 years after diagnosis, fasting proinsulin (10.0 ± 3.7 vs. 59.1 ± 17.0 pmol/l) and proinsulin responses to intravenous glucose (13.5 ± 5.4 vs. 103.9 ± 35.1 pmol/l) and to intravenous glucagon (7.4 ± 3.9 vs. 36.0 ± 7.7 pmol/l) were much lower (P < 0.01) in NIDDM patients with ICAs than in those without ICAs. CONCLUSIONS - After diagnosis of diabetes, proinsulin secretion decreases significantly in NIDDM patients with ICAs and remains constant in those without.
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