| 1. |
- Forsberg, Kalle, et al.
(författare)
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A Systematic Review Of Erythropoietin In Experimental Stroke
- 2009
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Ingår i: Stroke. - 0039-2499. ; 40:4
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Konferensbidrag (refereegranskat)abstract
- Introduction: Erythropoietin (EPO), a hematopoietic growth factor, has promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also is hypothesized to promote regeneration post stroke. Here we report a systematic review and meta-analysis of the published animal data characterizing the efficacy of EPO. Methods We conducted a systematic review and random effects weighted mean difference meta-analysis only including studies describing the efficacy of EPO in models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral score. A stratified analysis to identify the impact of elements of study quality and design was also conducted. Results Only 11 of 943 studies met our inclusion criteria. Infarct size was reported in 15 experiments using 191 animals. Neurobehavioral score was reported in 16 experiments using 287 animals. EPO improved infarct size by 30.5% (95%Cl 19.3%-41.7%) and neurobehavioral score by 37.4% (31.2– 43.7%). For infarct size, EPO was least effective in thrombotic models of ischemia, (16% versus to 44.8% and 24% in permanent and transient models of ischemia respectively, X2 =1.47 x 10–04). Using a scoring system derived from the STAIR criteria,study quality was modest with a median score of 4 out of 11 for both outcomes. Studies that randomized to treatment group reported smaller infarct sizes compared to those that did not (18.0% versus 44.8%, n=113 versus 78 animals, X2 = 3.4 x 10–05). Studies that blinded assessment of outcome also showed a smaller improvement in neurobehavioral score (31.1% versus 41.6%, n=107 versus 167, X2 = 8.9 x 10–4). Only 11.7% of the animals in the total dataset had a co-morbidity common to human stroke (hypertension) and this co-morbidity was only reported for neurobehavioral comparisons, not for infarct size. Blinded induction of ischemia was reported in 2 experiments (21.5% of animals) measuring infarct volume. Conclusions: Aggregation of the animal data for EPO in ischemic stroke indicates mean effect sizes of 30.5% and 37.4% for infarct volume and neurobehavioral score respectively. However, when the impact of common sources of bias are considered these effect sizes fall suggesting we are overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works would be beneficial before clinical trialing.
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| 2. |
- Nilsson, Peter, et al.
(författare)
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Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
- 2007
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
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| 3. |
- Fagman, Henrik, 1975, et al.
(författare)
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The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning.
- 2007
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:3, s. 276-85
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid dysgenesis is the major cause of congenital hypothyroidism in humans. The underlying molecular mechanism is in most cases unknown, but the frequent co-incidence of cardiac anomalies suggests that the thyroid morphogenetic process may depend on proper cardiovascular development. The T-box transcription factor TBX1, which is the most probable gene for the 22q11 deletion syndrome (22q11DS/DiGeorge syndrome/velo-cardio-facial syndrome), has emerged as a central player in the coordinated formation of organs and tissues derived from the pharyngeal apparatus and the adjacent secondary heart field from which the cardiac outflow tract derives. Here, we show that Tbx1 impacts greatly on the developing thyroid gland, although it cannot be detected in the thyroid primordium at any embryonic stage. Specifically, in Tbx1-/- mice, the downward translocation of Titf1/Nkx2.1-expressing thyroid progenitor cells is much delayed. In late mutant embryos, the thyroid fails to form symmetric lobes but persists as a single mass approximately one-fourth of the normal size. The hypoplastic gland mostly attains a unilateral position resembling thyroid hemiagenesis. The data further suggest that failure of the thyroid primordium to re-establish contact with the aortic sac is a key abnormality preventing normal growth of the midline anlage along the third pharyngeal arch arteries. In normal development, this interaction may be facilitated by Tbx1-expressing mesenchyme filling the gap between the pharyngeal endoderm and the detached thyroid primordium. The findings indicate that Tbx1 regulates intermediate steps of thyroid development by a non-cell-autonomous mechanism. Thyroid dysgenesis related to Tbx1 inactivation may explain an overrepresentation of hypothyroidism occurring in patients with the 22q11DS.
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| 4. |
- Fagman, Henrik, 1975, et al.
(författare)
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The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.
- 2006
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Ingår i: Developmental dynamics : an official publication of the American Association of Anatomists. - : Wiley. - 1058-8388. ; 235:2, s. 444-55
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Tidskriftsartikel (refereegranskat)abstract
- Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.
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| 5. |
- Hagnell, J, et al.
(författare)
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How to trap a slug: Commercial versus homemade slug traps
- 2006
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Ingår i: Crop Protection. - : Elsevier BV. - 1873-6904 .- 0261-2194. ; 25:3, s. 212-215
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Tidskriftsartikel (refereegranskat)abstract
- The Iberian Slug, Arion lusitanicus Mabille (Stylomatophora: Arionidae), has developed into a destructive pest in Swedish gardens and orchards over the past 10-20 years. Many attempts to eradicate this pest have been made using a variety of different methods. The aim of this study was to investigate the effectiveness of two different types of homemade traps made from simple, inexpensive materials (plastic PET bottle or an ice-cream box) compared to one type of commercially sold trap (Slugtrap((R)) IT-PAC A B, Sweden) used with bait and beer as attractants. Experiments were carried out on a private property outside Lund, Sweden, over a period of 7 days. The results showed that a homemade trap, i.e. a box trap, can be as efficient as a commercial trap, particularly due to their similar design. In contrast, the homemade bottle trap was not very successful. Additionally, it was discovered that the bait used in the commercial traps did not increase the number of slugs trapped. It was concluded that the beer was the main slug attractant. Ultimately this study suggests a low-cost alternative for small scale to the rather expensive commercially sold traps.
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| 6. |
- Lindencrona, Ulrika, 1971, et al.
(författare)
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Adsorption and volatility of free 211At and 125I-.
- 2005
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Ingår i: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. - : Elsevier BV. - 0969-8043. ; 62:3, s. 395-403
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Tidskriftsartikel (refereegranskat)abstract
- The present study was undertaken to extend our knowledge of the behaviour of 211At in the laboratory environment. An unexpectedly high volatility of free 211At was found, up to 85% during an hour. Free 211At also adsorbed more onto the plastic material studied than 125I-. The results of this study show that it is of great importance to pay careful attention to radiation protection procedures during the practical handling of free 211At.
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| 7. |
- Lindencrona, Ulrika, 1971, et al.
(författare)
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Transport of free 211At and 125I- in thyroid epithelial cells: effects of anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid on apical efflux and cellular retention.
- 2007
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Ingår i: Nuclear medicine and biology. - : Elsevier BV. - 0969-8051. ; 34:5, s. 523-30
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Astatine ((211)At; alpha-emitter; t(1/2)=7.21 h) shares several features with its halogen neighbour iodine. In the present study, we investigated whether 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) can be used to increase the cellular retention time of (211)At and radioiodide in thyroid epithelial cells. METHODS: The transepithelial transport and cellular uptake of (211)At and (125)I(-) were studied simultaneously in porcine thyrocytes cultured in bicameral chambers. The cells were prestimulated with thyroid-stimulating hormone (TSH) or epidermal growth factor (EGF) for 48 h. In addition, the acute effects of DIDS and forskolin were investigated. RESULTS: The transepithelial transport of both radionuclides was stimulated by TSH and down-regulated by EGF. DIDS rapidly reduced the efflux and increased the cellular content of (125)I(-) in control and TSH-stimulated cells, whereas DIDS had no effect on (125)I(-) transport in EGF-treated cells. DIDS blocked the (211)At efflux only in TSH-stimulated cells. Unexpectedly, DIDS caused an accelerated efflux of (211)At in both control and EGF-stimulated cells and, furthermore, reduced the cellular content of (211)At in the EGF-stimulated cultures. DIDS had no effect on the forskolin-induced efflux of the two radionuclides. CONCLUSIONS: The magnitude of thyroidal (211)At uptake and efflux is similar to that of (125)I(-), strongly dependent on the functional activity of the cells. However, (211)At efflux likely involves several permeating mechanisms with different sensitivity to DIDS, which are at least partly not shared by (125)I(-). The results suggest that anion channel blockage is potentially useful to increase the absorbed dose from both (211)At and radioiodine in NIS-expressing tumours.
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| 8. |
- Lundh, Charlotta, 1977, et al.
(författare)
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Biodistribution of free 211At and 125I- in nude mice bearing tumors derived from anaplastic thyroid carcinoma cell lines.
- 2006
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 21:6, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- Free 211At has been proposed for therapy of anaplastic thyroid carcinoma (ATC). However, no extensive biodistribution study comparing tumor-bearing and nontumor-bearing mice has previously been performed. The aim of this study was to perform a complete evaluation of the biodistribution of 211At, both for normal and ATC-bearing mice. For comparison, the biodistribution of 125I- was simultaneously studied. Dosimetric evaluations were performed to investigate if (211)At can be used for therapy of ATC. METHODS: Athymic nude mice were subcutaneously injected with either of two human ATC cell lines, HTh83 and KAT-4. Tumor-bearing and nontumor-bearing mice were injected intravenously with 0.3 MBq 211At and 0.3 MBq 125I- simultaneously. The mice were sacrificed 4-24 hours after injection, and the activity concentrations in tissues were determined. RESULTS: Except for the thyroid, the concentration of 211At was higher than that of 125I- in the tissues. The uptake of 211At was primarily high in NIS-expressing organs. Furthermore, the absorbed doses to these organs were higher than both tumor types. CONCLUSIONS: The biodistribution of 211At and 125I- differed in this animal model. The higher mean absorbed dose from 211At in several organs than in tumor tissue restricts the possibility of using free 211At for therapy of ATC.
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| 9. |
- Lundh, Charlotta, 1977, et al.
(författare)
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Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells.
- 2009
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505. ; 50:7, s. 1161-7
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Tidskriftsartikel (refereegranskat)abstract
- Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of (131)I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged (131)I for (123)I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that (131)I irradiation reduces iodide uptake by downregulating the expression of the sodium iodide symporter (NIS). The rationale for this study was therefore to study effects on iodide transport and NIS messenger RNA (mRNA) expression in thyrocytes exposed to both (123)I and (131)I in addition to some other potentially interesting radionuclides. METHODS: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of (123)I, (131)I, (99m)Tc, or (211)At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of (123)I or (131)I for 48 h. NIS mRNA expression was analyzed using quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Iodide transport and NIS mRNA expression were reduced by all radionuclides. At the same absorbed dose, iodide transport was reduced the most by (211)At, followed by (123)I and (99m)Tc (equally potent), whereas (131)I was least effective. The onset of NIS downregulation was rapid (<1 d after irradiation) in cells exposed to (123)I or (211)At and was delayed in cells irradiated with (131)I or (99m)Tc. Iodide transport and NIS expression were recovered only for (211)At. (123)I reduced the iodine transport and the NIS mRNA expression more efficiently than did (131)I at an equivalent absorbed dose, with a relative biological effectiveness of about 5. CONCLUSION: The stunning effect per unit absorbed dose is more severe for (123)I than for (131)I. Despite the lower absorbed dose per unit activity for (123)I than for (131)I, stunning by (123)I cannot be excluded in patients. The degree to which iodide transport capacity and NIS mRNA expression are reduced seems to be related to the biological effectiveness of the type of radiation delivering the absorbed dose to the target, with (211)At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.
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| 10. |
- Lundh, Charlotta, 1977, et al.
(författare)
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Reduced iodide transport (stunning) and DNA synthesis in thyrocytes exposed to low absorbed doses from 131I in vitro.
- 2007
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 48:3, s. 481-6
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid stunning refers to reduced uptake of (131)I in the thyroid tissue (or tumor) during radioiodine ((131)I) therapy compared with the uptake measured after the previous administration of (131)I for diagnostic purposes. The phenomenon is clinically important, as it can potentially lead to the undertreatment of thyroid cancer or to unnecessarily high absorbed doses in critical organs. Previous clinical and experimental studies indicated that thyroid stunning is absorbed dose dependent. The aim of this study was to investigate the effects of (131)I irradiation on (125)I(-) transport and cell proliferation at low absorbed doses in vitro. METHODS: Primary cultured porcine thyroid cells were grown to form a confluent monolayer of epithelial cells on a filter in a bicameral culture system. The cells were continuously irradiated with (131)I in the culture medium for 48 h to obtain 0.0015-1.5 Gy. At 3 d after irradiation was stopped, the transepithelial iodide transport capacity was evaluated by measuring (125)I(-) transport from the basal chamber compartment to the apical chamber compartment. The effect of (131)I irradiation on DNA synthesis was estimated by pulse labeling with (3)H-thymidine of both subconfluent and confluent cells irradiated with up to 9 Gy. Total DNA content was measured to quantify cell numbers. RESULTS: A statistically significant reduction in (125)I(-) transport was seen at absorbed doses of >or=0.15 Gy, with a 50% reduction at 1.5 Gy, compared with the results observed for nonirradiated control cells. (3)H-Thymidine incorporation was already statistically significantly reduced at absorbed doses of 0.01-0.1 Gy, but 0.15-0.3 Gy did not affect DNA synthesis. However, absorbed doses of >or=1 Gy again resulted in reduced DNA synthesis. A 50% reduction was obtained at 4 Gy. Total DNA measurements revealed a statistically significant reduction in cell numbers at 8 Gy. CONCLUSION: The lowest absorbed dose from (131)I that reduced iodide transport was 0.15 Gy. Because stunning was found at low absorbed doses, it might occur for (131)I treatment not only of thyroid cancer but also of thyrotoxicosis. On the basis of differences in dose responses, radiation-induced thyroid stunning and cell cycle arrest may be independent phenomena.
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