| 1. |
- Nowak, C., et al.
(författare)
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Intralymphatic GAD-Alum (Diamyd (R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2
- 2022
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:9, s. 2644-2651
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Tidskriftsartikel (refereegranskat)abstract
- Aims Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). Methods DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide > 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 mu g GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. Results We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time > 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. Conclusions Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
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| 2. |
- Gorovenko, N. G., et al.
(författare)
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The role of genetic determinant in the development of severe perinatal asphyxia
- 2010
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Ingår i: Cytology and genetics. - : Springer International Publishing AG. - 0095-4527. ; 44:5, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of GSTT1 and GSTM1 gene deletion polymorphism was determined in a case-control study of full-term Ukrainian newborns including patients with perinatal asphyxia. Multiplex polymerase chain reaction was used for genotyping 245 full-term newborns. The investigated full-term newborns with perinatal asphyxia were subdivided in the subgroups depending of severity of perinatal asphyxia and neonatal outcome. No significant differences in allele frequencies of homozygous null genotypes of GSTT1 and GSTM1 gene were detected among newborns with moderate perinatal asphyxia and healthy control. However, association with the development of severe perinatal asphyxia was detected for the deletion polymorphism in GSTT1 gene and the combination of the GSTT1 absent/GSTM1 absent in the newborns. The study shows that severe perinatal asphyxia may develop in the consequence of genetic predisposition to this condition as compare with moderate.
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| 3. |
- Håkansson, H., et al.
(författare)
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In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
- 1991
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
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| 4. |
- Ludvigsson, Johnny, et al.
(författare)
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Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:7, s. 1604-1612
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) <= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
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| 5. |
- Rundgren, S., et al.
(författare)
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Improvement of postpartum depression and psychosis after electroconvulsive therapy: A population-based study with a matched comparison group
- 2018
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 235, s. 258-264
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Electroconvulsive therapy (ECT) is used to treat postpartum depression and psychosis based on clinical experience and small observational studies. Aims: The primary aim was to test the hypothesis that the response rate to ECT for depression and psychosis is higher during the postpartum period than outside this period. The secondary aim was to identify predictors of a response to ECT during the postpartum period. Materials and methods: Cases with postpartum depression and/or psychosis received ECT within 6 months of delivery. A matched comparison group with depression and/or psychosis (not within the postpartum period) was identified from the Swedish National Quality Register for ECT. The improvement 1 week after ECT was classified according to the Clinical Global Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or non-responder (CGI-I score 3-7). Results: 185 cases and 185 comparison group subjects were included (46% with psychosis in each groups). More cases (87.0%) than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted binary regression analysis revealed that more severe symptoms prior to treatment were the only statistically significant predictor of response. Conclusion: The response rate of those with postpartum depression and/or psychosis to ECT was high. The response rate of patients with psychosis or depression was higher during the postpartum period than outside it. This study supports the use of ECT for severe forms of postpartum depression and/or psychosis.
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