| 1. |
- Darsalia, V., et al.
(författare)
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Exendin-4 Reduces Ischemic Brain Injury in Normal and Aged Type 2 Diabetic Mice and Promotes Microglial M2 Polarization
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed. Finally, the cellular mechanisms behind the efficacy of Exendin-4 have been only partially studied. The main objective of this study was to determine the neuroprotective efficacy of Exendin4 in normal and aged type 2 diabetic mice if the treatment started after stroke in a clinically relevant setting. Furthermore we characterized the Exendin-4 effects on stroke-induced neuroinflammation. Two-month-old healthy and 14-month-old type 2 diabetic/obese mice were subjected to middle cerebral artery occlusion. 5 or 50 mg/kg Exendin-4 was administered intraperitoneally at 1.5, 3 or 4.5 hours thereafter. The treatment was continued (0.2 mg/kg/day) for 1 week. The neuroprotective efficacy was assessed by stroke volume measurement and stereological counting of NeuN-positive neurons. Neuroinflammation was determined by gene expression analysis of M1/M2 microglia subtypes and proinflammatory cytokines. We show neuroprotective efficacy of 50 mg/kg Exendin-4 at 1.5 and 3 hours after stroke in both young healthy and aged diabetic/obese mice. The 5 mu g/kg dose was neuroprotective at 1.5 hour only. Proinflammatory markers and M1 phenotype were not impacted by Exendin-4 treatment while M2 markers were significantly up regulated. Our results support the use of Exendin-4 to reduce stroke-damage in the prehospital/early hospitalization setting irrespectively of age/diabetes. The results indicate the polarization of microglia/macrophages towards the M2 reparative phenotype as a potential mechanism of neuroprotection.
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| 2. |
- Roos Af Hjelmsäter, Emma, 1976, et al.
(författare)
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Children’s episodic memory: The effect of odour exposure during encoding and retrieval
- 2013
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Ingår i: Nordic Network for Research on Psychology and Law (NNPL), 2013-10-26, Århus, Dk.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction and aim. To help child witnesses recall relevant and detailed information, one may use sensory memory cues (e.g., as in the Cognitive Interview). However, in police interviews visual and auditory cues are often dominant, while potential cues from odour and taste are often ignored. To explore the efficacy of using odour as a memory cue, we set out to examine how odour interacts with memory. Methods. Children (N = 141, age 9-11) participated in a magic show where they either experienced, or did not experience, a vanilla odour. One week or six months later, they were interviewed about their memory of the magic show. During the interview they either experienced, or did not experience, the same vanilla odour. Results. Preliminary analyses showed that children who had been exposed to the odour during the magic show recalled less information, and with lower accuracy, compared to children who had not been exposed. There was no effect on memory of odour (re-)exposure during the interview. However, children who had been exposed to the odour during the interview rated their memory as being less emotional compared to children who had not been exposed. Conclusions. The preliminary results indicate that re-exposing children to an odour may not be useful in order to enhance memory. Moreover, a prominent odour during an event seems to impair memory performance. Exposing children to an odour during the interview may lead to their subjective emotionality being reduced, which is important as statements expressed with less emotion are often considered less reliable.
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| 3. |
- Swärd, Christina, 1967, et al.
(författare)
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[(177)Lu-DOTA(0)-Tyr (3)]-Octreotate Treatment in Patients with Disseminated Gastroenteropancreatic Neuroendocrine Tumors: The Value of Measuring Absorbed Dose to the Kidney.
- 2010
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 34, s. 1368-1372
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peptide receptor radiation therapy (PRRT) using [(177)Lu-DOTA(0)-Tyr(3)]-octreotate is a new, promising option for treatment of disseminated gastroenteropancreatic neuroendocrine tumors (GEPNETs). METHODS: During 2006-2008, 26 patients with disseminated GEPNETs were treated with (177)Lu-octreotate. Radiologic response (RECIST), biochemical response [plasma chromogranin-A (P-CgA)], hematologic toxicity [Common Toxicity Criteria (CTC)], absorbed dose to the kidneys (conjugate view method), and glomerular filtration rate (GFR) were analyzed. RESULTS: (177)Lu-octreotate (8 GBq) was given one to five times (median = 3) with a 6-week interval between each. Sixteen of the 26 patients were evaluated radiologically; 6 (38%) had partial response (PR), 8 (50%) had stable disease (SD), and 2 (13%) had progressive disease (PD). Seventeen of the 26 patients were evaluated biochemically; 6 (35%) showed a >/=30% decrease, 8 (47%) showed a >/=20% increase, and 3 (18%) showed neither a >/=30% decrease nor a >/=20% increase. The mean absorbed dose to the kidneys was 24 Gy. With a dose limit of 27 Gy to the kidneys, 10 patients did not receive the planned four treatments, while four patients had the potential to receive additional treatment. A significant reduction (p = 0.0013) of GFR was observed at follow-up. Three patients experienced CTC grade 3 hematologic toxicity. CONCLUSIONS: By using the absorbed dose to the kidneys as a limiting factor, treatment with (177)Lu-octreotate can be individualized, e.g., overtreatment can be avoided and patients with the potential to receive additional treatment can be identified. Further studies are needed to define tolerance doses to the kidneys so that treatment can be optimized.
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