Migrationsrättens lagstiftning har varit föremål för förändring vid ett flertal tillfällen, och reglerna gällande utvisning på grund av brott är nu under utredning. En efterfrågan av skärpning av ...reglerna har efterlysts politiskt, men frågan har även lyfts ett flertal gånger i media. Därtill har brottsförebyggande rådets rapport visat på en varierande grad av utvisningsbeslut. Syftet med uppsatsen har varit att utreda och analysera gällande lagstiftning om utvisning på grund av brott utifrån ett rättssäkerhetsperspektiv, i utredningen användes rättsdogmatisk metod som omfattar lagtext, förarbeten, praxis och doktrin. Uppsatsen utgår från en definition av begreppet rättssäkerhet och sedan presenteras relevant historia till ämnet. Därefter undersöktes förutsättningarna för att utvisas på grund av brott och vad domstolen ska ta hänsyn till i sin bedömning. Analysen av utredningen har visat att bestämmelserna generellt sett är tillfredställande utifrån ett rättssäkerhetsperspektiv med vissa tydliga brister.
Vad gör kyrkoherden? Hedin Magnus , Uppsala universitet, Pedagogiska institutionen
2009
Web Resource
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Provider: - Institution: - Data provided by Europeana Collections- Självständigt arbete på grundnivå (kandidatexamen)- 10 poäng / 15 hp- All metadata published by Europeana are available free of ...restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy ...significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Provider: Swedish Open Cultural Heritage | K-samsök - Institution: Örebro läns museum - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction ...under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Purpose
AlzeCure Pharma AB is developing novel positive allosteric modulators of Trk-receptors for treatment of Alzheimer’s disease, depression, other psychiatric conditions and other disorders where ...cognition is impaired. The preceding candidate drug ACD855 was shown to have a too long half-life in humans to allow further development. To de-risk the development of the follow-up compound ACD856, the oral single ascending dose study of ACD856 in humans was preceded by an intravenous microdose study, assessing the elimination half-life in plasma.
Methods
A phase 0 study with a microdose of ACD856 (0.100 mg), was conducted in six healthy male subjects all receiving ACD856. Sequentially, a randomized, placebo-controlled, double-blind Phase I single ascending oral dose study (1 – 150 mg) was conducted, including 56 healthy subjects. Both studies assessed the safety and tolerability, as well as the PK properties of ACD856 after single dose intravenous and oral administration.
Results
ACD856 was well tolerated with no treatment emergent, or dose related adverse events or other safety assessments. In the microdose study, ACD856 exhibited a bi-exponential plasma decline, low distribution volume, low plasma clearance with a half-life of approximately 20 hours. Orally, ACD856 exhibited rapid absorption, an almost complete bioavailability and a dose proportional increase in exposure. While the C
max
was lowered and delayed by food intake, the effect on plasma half-life and the overall bioavailability was low. No renal elimination of ACD856 was detected.
Conclusion
The prediction proved accurate demonstrating the value of conducting a microdose study prior to ascending dose studies.
Trial registration
NCT05783830 March 24, 2023 (microdose study, retrospectively registered) and NCT05077631 October 14, 2021 (single ascending dose study).
Laminins are essential components of the endothelial basement membrane, which predominantly contains LN421 and LN521 isoforms. Regulation of laminin expression under pathophysiological conditions is ...largely unknown. In this study, we aimed to investigate the role of IL-6 in regulating endothelial laminin profile and characterize the impact of altered laminin composition on the phenotype, inflammatory response, and function of endothelial cells (ECs).
HUVECs and HAECs were used for in vitro experiments. Trans-well migration experiments were performed using leukocytes isolated from peripheral blood of healthy donors. The BiKE cohort was used to assess expression of laminins in atherosclerotic plaques and healthy vessels. Gene and protein expression was analyzed using Microarray/qPCR and proximity extension assay, ELISA, immunostaining or immunoblotting techniques, respectively.
Stimulation of ECs with IL-6+sIL-6R, but not IL-6 alone, reduces expression of laminin α4 (LAMA4) and increases laminin α5 (LAMA5) expression at the mRNA and protein levels. In addition, IL-6+sIL-6R stimulation of ECs differentially regulates the release of several proteins including CXCL8 and CXCL10, which collectively were predicted to inhibit granulocyte transmigration. Experimentally, we demonstrated that granulocyte migration is inhibited across ECs pre-treated with IL-6+sIL-6R. In addition, granulocyte migration across ECs cultured on LN521 was significantly lower compared to LN421. In human atherosclerotic plaques, expression of endothelial LAMA4 and LAMA5 is significantly lower compared to control vessels. Moreover, LAMA5-to-LAMA4 expression ratio was negatively correlated with granulocytic cell markers (CD177 and myeloperoxidase (MPO)) and positively correlated with T-lymphocyte marker CD3.
We showed that expression of endothelial laminin alpha chains is regulated by IL-6 trans-signaling and contributes to inhibition of trans-endothelial migration of granulocytic cells. Further, expression of laminin alpha chains is altered in human atherosclerotic plaques and is related to intra-plaque abundance of leukocyte subpopulations.
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•IL-6 trans-signaling induces LAMA4-to-LAMA5 switch in endothelial cells, which is accompanied by secretion of several inflammatory mediators.•These alterations contribute to favored trans-endothelial migration of mononuclear cells over granulocytic cells.•In human atherosclerotic plaques, the expression of LAMA4 and LAMA5 is altered and correlates with markers of granulocytic and lymphocytic cells.
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