| 1. |
- Baslund, B, et al.
(författare)
-
Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells
- 2008
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 47:4, s. 451-453
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells. METHODS: Mononuclear cells were isolated from peripheral blood of healthy persons. Real-time PCR was used to detect the RFC80 variants. FITC-labelled MTX was added to cells stimulated with Candida albicans or tetanus toxoid, and the uptake of MTX was measured by flow cytometry. A FITC-conjugated monoclonal antibody against RFC was used to detect the cellular RFC expression. RESULTS: Antigen-stimulated CD4+ T cells and B cells from individuals with the GG variant (n = 9) exhibited lower uptake of MTX than individuals expressing the AA variant (n = 8), or the GA variant (n = 8). No difference could be demonstrated between the three groups with respect to the expression of RFC by CD4+ T cells and B cells, and CD4+ T cells from individuals homozygous for the G allele exhibited lower uptake of MTX per receptor than CD4+ T cells from individuals homozygous for the A allele. CONCLUSION: MTX is taken up more efficiently via the A allele than via the G allele. This difference between the variant forms of RFC suggests that genotyping could be relevant for determining the relevant dosage of MTX in the treatment of neoplastic and autoimmune disease.
|
|
| 2. |
- Christensen, Dirk L., et al.
(författare)
-
Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life
- 2023
-
Ingår i: Frontiers in Public Health. - 2296-2565. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. Methods: We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. Results: No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. Conclusion: The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.
|
|
| 3. |
- Licht, Rasmus W., et al.
(författare)
-
Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6)
- 2010
-
Ingår i: Bipolar Disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 12:5, s. 483-493
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: In industry-generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions. Methods: Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5-1.0 mmol/L) or to lamotrigine (n = 77; up-titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models. Results: For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60-1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73-5.04) and 0.69 (95% CI: 0.41-1.22). There was no between-group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61-1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium-treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine-related, of benign rash occurred. Conclusions: No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome.
|
|
| 4. |
- Linnebjerg, Jannie Fries, et al.
(författare)
-
Deciphering the structure of the West Greenland marine food web using stable isotopes (δ13C, δ15N)
- 2016
-
Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 163:11
-
Tidskriftsartikel (refereegranskat)abstract
- The Arctic is facing major environmental changes impacting marine biodiversity and ecosystem functioning. One way of assessing the responses of an ecosystem to these changes is to quantitatively study food web dynamics. Here, we used stable isotope (δ15N and δ13C) analyses of 39 Arctic marine species to investigate trophic relationships and isotopic niches of the West Greenland food web in 2000–2004. The lowest δ15N values were found for suspension feeding blue mussel (Mytilus edulis; 6.1 ‰) and the highest for polar bear (Ursus maritimus; 20.2 ‰). For δ13C, copepods (Calanus spp.) had the lowest values (−20.4 ‰) and snow crab (Chionoecetes opilio) the highest values (−15.8 ‰). Our results show that the three trophic enrichment factor (TEF) approaches used to quantify species trophic positions (fixed TEF of 3.8 and 3.4 ‰ or scaled TEF) did not generally affect trophic modelling and provided similar conclusions. Overall, the findings in this study are in good agreement with previous investigations of other Arctic marine ecosystems. Interestingly, we found little overlap of core isotopic niches used by the four investigated functional groups (mammals, seabirds, fish and invertebrates), except for seabirds and fish where an overlap of 24 % was found. These results provide new insights into species and functional group interactions, as well as into the food web structure and ecosystem functioning of an important Arctic region that can be used as a template to guide future modelling of carbon, energy and contaminant flow in the region.
|
|
