| 1. |
- Prokopenko, Inga, et al.
(author)
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A Central Role for GRB10 in Regulation of Islet Function in Man.
- 2014
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:4
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Journal article (peer-reviewed)abstract
- Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
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| 2. |
- Säll-Hansson, Karin, et al.
(author)
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The meaning of the experiences of persons with chronic pain in their encounters with the health service
- 2011
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In: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 25:3, s. 444-450
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Journal article (peer-reviewed)abstract
- The meaning of the experiences of persons with chronic pain in their encounters with the health service Chronic pain causes great suffering for those affected and treating it is one of the most common assignments in the health service. The aim of the study was to investigate the meaning of the experiences of persons with chronic pain in their encounters with health service staff. The study had a descriptive design with a phenomenological approach based on the perspective of caring science. Interviews were carried out with eight patients. The study showed that patients experienced a positive approach and that the staff had understood the serious nature of the situation. A positive approach can communicate hope and help to strengthen the patient. It is important to ask the patient about how he/she experiences his/her situation and thus gain an insight into this person's lifeworld. Participation entailed being active oneself and calling attention to one's needs and wishes for treatment. The study also showed that a negative approach by the staff played a prominent part in their experiences and appeared to be engraved in their memories. A negative approach is felt as being insulting and belittling. Patients with chronic pain felt that they were discredited and that their experience of their situation was called into question. They had to fight to get care and had to suggest treatments and examinations. There were also patients who had neither been asked about their pain experience nor had the opportunity to assess their pain with an assessment scale. Some of the phases in Travelbee's relationship model could be seen in several of the encounters but not all. The participants did not always feel that the manner of the nursing staff was empathetic or sympathetic, which led to greater suffering.
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| 3. |
- Adermark, Louise, 1974, et al.
(author)
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Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens.
- 2011
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In: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 16:1, s. 43-54
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Journal article (peer-reviewed)abstract
- ABSTRACT Elevated dopamine levels are believed to contribute to the rewarding sensation of ethanol (EtOH), and previous research has shown that strychnine-sensitive glycine receptors in the nucleus accumbens (nAc) are involved in regulating dopamine release and in mediating the reinforcing effects of EtOH. Furthermore, the osmoregulator taurine, which is released from astrocytes treated with EtOH, can act as an endogenous ligand for the glycine receptor, and increase extracellular dopamine levels. The aim of this study was to address if EtOH-induced swelling of astrocytes could contribute to elevated dopamine levels by increasing the extracellular concentration of taurine. Cell swelling was estimated by optical sectioning of fluorescently labeled astrocytes in primary cultures from rat, and showed that EtOH (25-150 mM) increased astrocyte cell volumes in a concentration- and ion-dependent manner. The EtOH-induced cell swelling was inhibited in cultures treated with the Na(+)/K(+)/2Cl(-) cotransporter blocker furosemide (1 mM), Na(+)/K(+)-ATPase inhibitor ouabain (0.1 mM), potassium channel inhibitor BaCl(2) (50 microM) and in cultures containing low extracellular sodium concentration (3 mM). In vivo microdialysis performed in the nAc of awake and freely moving rats showed that local treatment with EtOH enhanced the concentrations of dopamine and taurine in the microdialysate, while glycine and beta-alanine levels were not significantly modulated. EtOH-induced dopamine release was antagonized by local treatment with the glycine receptor antagonist strychnine (20 microM) or furosemide (100 microM or 1 mM). Furosemide also prevented EtOH-induced taurine release in the nAc. In conclusion, our data suggest that extracellular concentrations of dopamine and taurine are interconnected and that swelling of astrocytes contributes to the acute rewarding sensation of EtOH.
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| 4. |
- Ahlqvist, Emma, et al.
(author)
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A link between GIP and osteopontin in adipose tissue and insulin resistance.
- 2013
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2088-2094
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Journal article (peer-reviewed)abstract
- Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.
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| 5. |
- Anderson, Ulrik Dolberg, et al.
(author)
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Gene expression profiling of first trimester placentas from pregnancies at high risk of developing preeclampsia
- 2013
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In: Pregnancy Hypertension. - : Elsevier BV. - 2210-7789. ; 3:2, s. 69-69
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Conference paper (peer-reviewed)abstract
- INTRODUCTION: Preeclampsia (PE) is an important cause of fetal and maternal morbidity and mortality. It is considered a two-stage disease, the first stage characterized by a defect placentation and the second stage by maternal manifestations. Details of the patho-physiology behind the transition from stage one to stage two remain unclear.OBJECTIVE: Was to study first trimester placental gene expression in patients identified as high risk for PE by either Doppler ultrasound or the biochemical markers cell free fetal hemoglobin (HbF) and alpha-1-microglobulin (A1M).METHODS: Placental samples were obtained from seven women at highrisk of PE as determined by Doppler ultrasound of the uterine arteries and eight women with normal uterine artery resistance who for other reasons terminated their pregnancies surgically. Maternal serum samples were analyzed for HbF and A1M. The patients were risk stratified according to two risk classifications: (I) High vs. low uterine artery resistance and (II) High HbF and A1M vs. low HbF and A1M. Total RNA from the placentas was used for whole genome microarray. The results were analyzed by bioinformatics and genes of interest confirmed with qPCR.RESULTS: A total of 453 and 332 significantly altered genes were identified in the two study groups. Bioinformatics revealed 12 genes of interest in study group I and 7 genes of interest in study group II.CONCLUSIONS: Genes related to vascular tonus regulation and inflammatory response were identified in study group I suggesting that a lack of tonus regulation and increased inflammation might contribute to the high uterine artery resistance seen in this group. Genes related to regulation of hematopoiesis was found in group II suggesting dysfunctional hematopoiesis as a factor explaining the high levels of cell-free HbF seen.
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| 6. |
- Annergren, Mariette, et al.
(author)
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An ADMM Algorithm for Solving l(1) Regularized MPC
- 2012
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In: 2012 IEEE 51st Annual Conference on Decision and Control (CDC). - : IEEE. - 9781467320665 ; , s. 4486-4491
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Conference paper (peer-reviewed)abstract
- We present an Alternating Direction Method of Multipliers (ADMM) algorithm for solving optimization problems with an ℓ1 regularized least-squares cost function subject to recursive equality constraints. The considered optimization problem has applications in control, for example in ℓ1 regularized MPC. The ADMM algorithm is easy to implement, converges fast to a solution of moderate accuracy, and enables separation of the optimization problem into sub-problems that may be solved in parallel. We show that the most costly step of the proposed ADMM algorithm is equivalent to solving an LQ regulator problem with an extra linear term in the cost function, a problem that can be solved efficiently using a Riccati recursion. We apply the ADMM algorithm to an example of ℓ1 regularized MPC. The numerical examples confirm fast convergence to sufficient accuracy and a linear complexity in the MPC prediction horizon.
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| 7. |
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| 8. |
- Dolberg Anderson, Ulrik, et al.
(author)
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Fetal hemoglobin and alpha(1)-microglobulin as first- and early second-trimester predictive biomarkers for preeclampsia
- 2011
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 204:6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to evaluate fetal hemoglobin (HbF) and alpha(1)-microglobulin (A1M) in maternal serum as first-trimester biomarkers for preeclampsia (PE). STUDY DESIGN: The design was a case-control study. We included 96 patients in the first trimester of pregnancy (60 with PE and 36 controls). Venous serum samples were analyzed for HbF and total hemoglobin (Hb) by enzyme-linked immunosorbent assay and for A1M by radioimmunoassay. Sensitivity and specificity was calculated by logistic regression and receiver operating characteristic curve analysis. RESULTS: The HbF/Hb ratio and A1M concentration were significantly elevated in serum from women with subsequent development of PE (P < .0001). The optimal sensitivity and specificity was obtained using the biomarkers in combination; 69% sensitivity for a 5% screen positive rate and 90% sensitivity for a 23% screen positive rate. CONCLUSION: The study suggests that HbF/Hb ratio in combination with A1M is predictive biomarkers for PE.
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| 9. |
- Dolberg Anderson, Ulrik, et al.
(author)
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Review: Biochemical markers to predict preeclampsia.
- 2012
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In: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 33, s. 42-47
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Journal article (peer-reviewed)abstract
- Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α(1)-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births.
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| 10. |
- Edström-Hägerwall, Anneli, et al.
(author)
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Alpha-1-microglobulin protects from heme induced placenta and kidney damage in a pregnant ewe model for preeclampsia
- 2013
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In: Pregnancy Hypertension. - : Elsevier BV. - 2210-7789. ; 3:2, s. 1-70
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Conference paper (peer-reviewed)abstract
- INTRODUCTION: Previous gene expression analysis have identified fetal hemoglobin (HbF) as a plausible etiological factor in preeclampsia. Free hemoglobin and its degradation products, e.g. heme, are known to cause oxidative stress, tissue damage, and vaso-constriction, typical findings in preeclampsia.OBJECTIVE: To study alpha-1-microglobulin (A1M), an endogenous radical scavenger and heme-binder, as a potential treatment for preeclampsia using the pregnant ewe preeclampsia model. Free Hb and heme are known to take part in the pathology of this model and therefor well suited for evaluation of recombinant A1M as a therapy.METHODS: 11 pregnant ewes, at gestational age 125-131 days, were acclimatized for 36h and then starved for another 36h to induce preeclampsia symptoms. At the end of starvation period, they were treated either with placebo (n=6) or A1M injections (n=5). After injections, food was re-introduced and ewes further followed for 72h. The ewes were sacrificed the 6th day after beginning of acclimatization. Throughout the 6 days, the animals were monitored for blood pressure and different blood and urine parameters. Whole blood, kidney and placenta tissue samples were collected from the ewes. Gene expression analysis, blood analysis, histology and electron microscopy were used to evaluate the therapeutic effects of A1M.RESULTS: Starvation increased the amount of free heme in the blood. The ultrastructure of the placenta and kidney were damaged in a way similar to what previously have been described for PE. The glomeruli and the tubuli were damaged which was reflected by increased Ficol clearance and increased plasma creatinine levels. Treatment with A1M significantly normalized the kidney functions. The most profound changes on gene expression level were found in white blood cells in the starved animals. Starvation decreases mRNA expression for anti-oxidants such as CAT (P=0.04), SOD1 (P=0.008), SOD2 (1.8-fold) as well as angiogenetic factors such as VEGF (P=0.02) and HGF (1.6-fold). A1M treatment rescued the decreased expression of SOD2 (P=0.04) and HGF (2-fold).CONCLUSION: A1M is well tolerated and shows high potential as a treatment for PE-like symptoms in the pregnant ewe model for PE.
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