| 21. |
- Rugarn, Olof, et al.
(författare)
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Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain
- 1999
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Ingår i: Peptides. - 0196-9781 .- 1873-5169. ; 20:6, s. 743-748
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.
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| 22. |
- Rugarn, Olof, et al.
(författare)
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Sex differences in neuropeptide distribution in the rat brain
- 1999
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Ingår i: Peptides. - 0196-9781 .- 1873-5169. ; 20:1, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.
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| 23. |
- Sinkvist, David, et al.
(författare)
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Five Year Data and Results of Continuous Quality Improvement Using SKURT
- 2017
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Ingår i: Educational Research Applications. - IL, USA : Gavin Publishers. - 2575-7032. ; 2017:05
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Tidskriftsartikel (refereegranskat)abstract
- Student rating of teaching isessentialfor attaining and maintaining higheducational quality.A quality improvement system, SKURT,based on digital online weekly combined quantitative, ten-graded scale, and qualitative, open-ended free text, group feedback from medical students was developed. Students rated all educational, non-clerkship, items throughout the entire medical program, spanning eleven terms. The results were semi-publicly available for students and faculty at a Swedish university. This study describes datafrom five-year use of the system,focusing on how the use of SKURT influenced educational items found to be in the most substantial need for improvements.Statistically but hardly practically significant improvement in average feedback grade was found during the observation period (average 7.07 in 2009 to 7.24 in 2013 (p<0.001)).The medical program was already in 2007recognized ascenter of excellent quality in higher education. When analyzing the 18 lectures with lowest outcome in the spring 2009 compared to the fall 2013, five were discontinued. The remaining 13 lectures improved significantly (p<0.001) 116% from 2.94 (SD 0.92) to 6.34 (SD 2.58). A weekly group feedback system employing the principles used in SKURTis useful forimproving the quality of medical education particularlyby improvingthe items with the lowest ratings.
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| 24. |
- Sinkvist, David, 1986-, et al.
(författare)
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SKURT: Quality Improvement System with Comprehensive Weekly Digital Student Group Feedback
- 2017
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Ingår i: Educational Research Applications. - : Gavin Publishers. - 2575-7032. ; 2017:5
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Tidskriftsartikel (refereegranskat)abstract
- Students’ role in evaluation and rating of teachers and education has been extensively researched for nearly a century. Applied worldwide, students’ ratings account for the majority of the available data.We created a new quality improvement system, SKURT, using digital online weekly combined quantitative, ten-graded scale, and qualitative, open-ended free text, group feedback from medical students. Students rated all educational, non-clerkship, items throughout the entire medical program, spanning eleven terms. The rating process is since 2008 an integral part of a medical program at a Swedish university. The results are, after a screening process, semi-publicly available on-demand, for students and faculty, creating a feedback loop enabling continuous improvement of quality.A thorough literature search of students rating of teaching found no other corresponding weekly group rating system spanning all educational items. Quality improvement systems based on similar principles as SKURT can uncover problem areas that are difficult to find using other rating systems and has the potential to circumvent several biases, risks and shortcomings of traditional rating systems in current use.
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| 25. |
- Ström, Jakob, et al.
(författare)
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Effects of high and low 17 beta-estradiol doses on focal cerebral ischemia: negative results
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17 beta-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.
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| 26. |
- Ström, Jakob, et al.
(författare)
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Effects of high and low 17β-estradiol doses on cerebral ischemia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Estrogens’ effects on cerebral ischemia have during the last two decades been the subject of intense research efforts. Notwithstanding this, the reasons that some studies indicate that estrogens are damaging while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for this dichotomy. The current study was designed to test this ypothesis.METHODS: Sixty ovariectomized female rats were randomized into three groups differing in subsequent 17β-estradiol regimen (vehicle, low dose and high dose respectively). Following two weeks of treatment, focal cerebral ischemia was induced via an intraluminal filament middle cerebral artery occlusion (MCAo) method. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment.RESULTS AND DISCUSSION: The hormone administration regimens significantly affected animal weights and feeding behavior, but infarct sizes did not differ between groups. Further, random intra-group variations in infarct size were too large to allow negative conclusions to be drawn. The large variation was possibly a consequence of too large occluding filament diameter in combination with that the animals were allowed to wake up during ongoing MCAo. After correcting the large variation, the hypothesis needs to be addressed anew.
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| 27. |
- Ström, Jakob, et al.
(författare)
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Mechanisms of estrogens' dose-dependent neuroprotective and neurodamaging effects in experimental models of cerebral ischemia
- 2011
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Ingår i: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI AG. - 1661-6596 .- 1422-0067. ; 12:3, s. 1533-1562
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Forskningsöversikt (refereegranskat)abstract
- Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings.
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| 28. |
- Ström, Jakob, et al.
(författare)
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Method parameters’ impact on mortality and variability in rat stroke experiments : a meta-analysis
- 2013
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Ingår i: BMC Neuroscience. - London, United Kingdom : BioMed Central. - 1471-2202. ; 14:41
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEven though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains.MethodsWe therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability.ResultsThe Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method.ConclusionsThe current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality.
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| 29. |
- Ström, Jakob O, et al.
(författare)
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Different methods for administering 17 beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage
- 2010
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Ingår i: BMC Neuroscience. - London, United Kingdom : BioMed Central. - 1471-2202. ; 11, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17 beta-estradiol administration; home-made silastic capsules instead of commercial slow-release 17 beta-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17 beta-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.Results: In contrast to our earlier results using the commercial pellets, the group receiving 17 beta-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean +/- SEM: 3.85 +/- 0.70% versus 7.15 +/- 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17 beta-estradiol was administered only during the two weeks before or the three days immediately after MCAo.Conclusions: The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.
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| 30. |
- Ström, Jakob O, et al.
(författare)
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Dose-related neuroprotective versus neurodamaging effects of estrogens in rat cerebral ischemia : a systematic analysis
- 2009
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - New York, USA : SAGE Publications. - 0271-678X .- 1559-7016. ; 29:8, s. 1359-1372
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Forskningsöversikt (refereegranskat)abstract
- Numerous studies of the effects of estrogens for stroke prevention have yielded conflicting results in human and animal studies alike. We present a systematical analysis of study design and methodological differences between 66 studies where estrogens impact on ischemic brain damage in rat models has been investigated, providing evidence that the differences in results may be explained by high estrogen doses produced by slow-release pellets. These pellets have been used in all studies showing increased neurologic damage because of estrogens. Our data indicate that the increased neurologic damage is related to the pellets plasma concentration profile with an early, prolonged, supraphysiological peak. Neither the method of inducing the ischemic brain lesions, the choice of variables for measuring outcome, the measured plasma concentrations of estrogens at the time of ischemia nor rat population attributes (sex, strain, age, and diseases) are factors contributing to the discrepancies in results. This suggests that the effects of estrogens for stroke prevention are concentration related with a complex dose-response curve, and underscores the importance of carefully validating the experimental methods used. Future studies of hormone-replacement therapy in women may have to take dosage and administration regimens into account.
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