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  • Ortqvist, E., et al. (författare)
  • Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes
  • 2004
  • Ingår i: Diabetes Care. - 0149-5992 (Print). ; 27:9, s. 2191-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
  • Sherry, Nicole, et al. (författare)
  • Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial
  • 2011
  • Ingår i: The Lancet. - Elsevier. - 0140-6736 .- 1474-547X. ; 378:9790, s. 487-497
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve beta-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. less thanbrgreater than less thanbrgreater thanMethods In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protege study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0.5 U/kg per day and glycated haemoglobin A(1c) (HbA(1c)) of less than 6-5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. less thanbrgreater than less thanbrgreater thanFindings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19.8% (41/207) in the 14-day full-dose group; 13.7% (14/102) in the 14-day low-dose group; 20.8% (22/106) in the 6-day full-dose group; and 20.4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0.03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). less thanbrgreater than less thanbrgreater thanInterpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in beta-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.</p>
  • Viskari, H, et al. (författare)
  • Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies : Time trends and geographical variation
  • 2005
  • Ingår i: Diabetologia. - 0012-186X .- 1432-0428. ; 48:7, s. 1280-1287
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aims/hypothesis: We have previously observed an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. The aim of this study was to analyse whether maternal enterovirus antibody status, which reflects both the frequency of enterovirus infections and the protection conferred by the mother on the offspring, also correlates with the incidence of type 1 diabetes. Methods: Maternal enterovirus antibodies were analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden using enzyme immunoassay and neutralisation assays. Comparable samples were also taken between 1999 and 2001 in countries with a lower incidence of diabetes (Estonia, Germany, Hungary, Israel, Lithuania, Russia). Results: A clear decrease was observed in maternal enterovirus antibody levels over the past 20 years (p<0.0001). The frequency of enterovirus antibodies was higher in countries with a low or intermediate incidence of type 1 diabetes compared with high-incidence countries (p<0.0001). Conclusions/interpretation: These findings are in line with our previous observations supporting the hypothesis that a low frequency of enterovirus infection in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses. © Springer-Verlag 2005.</p>
  • Emilsson, L., et al. (författare)
  • The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease
  • 2013
  • Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036. ; 37:9, s. 905-914
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors. Aim To characterise IHD according to CD status. Methods Data on duodenal or jejunal biopsies were collected in 20062008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals. Results We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P&lt;0.001) and cholesterol values (P&lt;0.001) and were less likely to be active smokers (OR=0.74; 95% CI=0.560.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR=0.80; 95% CI=0.660.97; three-vessel disease: OR=0.73; 95% CI=0.570.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P=0.766). Conclusion Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.</p>
  • Hallberg, R. T., et al. (författare)
  • Hydrogen-assisted spark discharge generated metal nanoparticles to prevent oxide formation
  • 2018
  • Ingår i: Aerosol Science and Technology. - Taylor & Francis. - 0278-6826. ; 52:3, s. 347-358
  • Tidskriftsartikel (refereegranskat)abstract
    • There exists a demand for production of metal nanoparticles for today's emerging nanotechnology. Aerosol-generated metal nanoparticles can oxidize during particle formation due to impurities in the carrier gas. One method to produce unoxidized metal nanoparticles is to first generate metal oxides and then reduce them during sintering. Here, we propose to instead prevent oxidation by introducing the reducing agent already at particle formation. We show that by mixing 5% hydrogen into the nitrogen carrier gas, we can generate single crystalline metal nanoparticles by spark discharge from gold, cobalt, bismuth, and tin electrodes. The non-noble nanoparticles exhibit signs of surface oxidation likely formed post-deposition when exposed to air. Nanoparticles generated without hydrogen are found to be primarily polycrystalline and oxidized. To demonstrate the advantages of supplying the reducing agent at generation, we compare to nanoparticles that are generated in nitrogen and sintered in a hydrogen mixture. For bismuth and tin, the crystal quality of the particles after sintering is considerably higher when hydrogen is introduced at particle generation compared to at sintering, whereas for cobalt it is equally effective to only add hydrogen at sintering. We propose that hydrogen present at particle generation prevents the formation of oxide primary particles, thus improving the ability to sinter the nanoparticles to compact and single crystals of metal. This method is general and can be applied to other aerosol generation systems, to improve the generation of size-controlled nanoparticles of non-noble metals with a suitable reducing agent.
  • Kohut, A., et al. (författare)
  • From plasma to nanoparticles : Optical and particle emission of a spark discharge generator
  • 2017
  • Ingår i: Nanotechnology. - IOP Publishing. - 0957-4484. ; 28:47
  • Tidskriftsartikel (refereegranskat)abstract
    • The increased demand for high purity nanoparticles (NPs) of defined geometry necessitates the continuous development of generation routes. One of the most promising physical techniques for producing metal, semiconductor or alloy NPs in the gas phase is spark discharge NP generation. The technique has a great potential for up-scaling without altering the particles. Despite the simplicity of the setup, the formation of NPs in a spark discharge takes place via complex multi-scale processes, which greatly hinders the investigation via conventional NP measurement techniques. In the present work, time-resolved optical emission spectroscopy (OES) was used to provide information on the species present in the spark from as early as approximately 100 ns after the initiation of the discharge. We demonstrate that operando emission spectroscopy can deliver valuable insights into NP formation. The emission spectra of the spark are used to identify, among others, the main stages of material erosion and to calculate the quenching rate of the generated metal vapour. We demonstrate that the alteration of key control parameters, that are typically used to optimize NP generation, clearly affect the emission spectra. We report for Cu and Au NPs that the intensity of spectral lines emitted by metal atoms levels off when spark energy is increased above an energy threshold, suggesting that the maximum concentration of metal vapour produced in the generator is limited. This explains the size variation of the generated NPs. We report a strong correlation between the optical and particle emission of the spark discharge generator, which demonstrate the suitability of OES as a valuable characterization tool that will allow for the more deliberate optimization of spark-based NP generation.
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