Functionalized polyhedral oligosilsesquioxanes (POSS) containing an isoxazolidine nucleus have been synthesized by microwave assisted 1,3-dipolar cycloaddition of
N
-methyl-
C
-alkoxycarbonyl nitrone
...1
with POSS containing olefin moieties. The results of cycloaddition processes were rationalized by computational studies at the DFT level. The covalent conjugation of chitosan with the cycloadduct
3a
leads to composite material CS-POSS
7
which was gelified using genipin as cross linking agent. The suitability of the system for bone tissue engineering purposes was evaluated by
in vitro
drug release studies using ketoprofen as a model drug and cytotoxicity assays performed on human fetal osteoblastic cells. The preliminary biological tests showed the lack of cytotoxicity of the hybrid material and suggest its potential role in bone tissue engineering applications.
Functionalized POSS containing an isoxazolidine nucleus have been synthesized by 1,3-dipolar cycloaddition and conjugated with chitosan for bone tissue engineering applications.
Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these ...different genetic aetiologies result in distinct clinical features.
Retrospective analysis of the Italian data set of patients with TNDM.
Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared.
Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy.
If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
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