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Biomedical subjects

Cecilia Mattsson

Publications and source records attributed to Cecilia Mattsson.

7 recordsLinked to original sources

2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists.

A series of 2-alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles were synthesized and evaluated for their 5-HT6 activity. The most potent agonist in this series was 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole with an IC50=7.4 nM in 3H-LSD binding and an EC50=1.0 nM in a functional assay measuring production of cyclic AMP.

Cell Line↗

Hyaluronan is differently located in arteries and veins. An immunohistochemical study in the rat.

The matrix components of the vessel wall are of great importance for the function of the vessel system of which both endurance and elasticity are prerequisites. One component of the vessel wall is the glycosaminoglycan hyaluronan (HYA) with its unique physico-chemical properties, e.g. viscoelasticity and barrier function. The present study aimed to map and compare the normal localisation and distribution of hyaluronan in the arteries and veins of both adult and newborn rats, using a specific staining method utilizing a hyaluronan-binding protein. The hyaluronan stained clearly different in veins and arteries both in newborn and adult rats. In the veins, the tunica intima stained intensely whereas the corresponding area in the arteries only showed a weak and scattered staining pattern. In the adult rats, the matrix between the smooth muscle cells of the tunica media of the veins had a clearly positive staining pattern compared to the media in the arteries which showed only a few scattered areas of positive staining. In the newborn rats, the media of the arteries stained more intensely. In both newborn and adult rats, the adventitia stained intensely both in veins and arteries. Moreover, the HYA-staining pattern differed in veins in different regions of the body. Since HYA is known to be involved in many different biological processes, the results are of importance to understand physiological properties of the vessel tree and to explain the development of vascular diseases.

Animals↗

First forty-eight hours of developing otitis media: an experimental study.

The early inflammatory changes in the tympanic membrane were explored in 2 rat models. Acute otitis media was induced by instillation of Streptococcus pneumoniae type 3 into the middle ear cavity, and otitis media with effusion was induced by blockage of the eustachian tube. Otomicroscopic examination was performed before the rats were painlessly sacrificed at 3, 6, 9, 12, 18, 24, or 48 hours after initiation of the otitis media conditions. The tympanic membrane was studied by light and electron microscopy. Both acute otitis media and otitis media with effusion caused early inflammatory changes of the tympanic membrane, and the pars flaccida was the portion that reacted first. The inflammatory alterations were most pronounced in the acute otitis media model. The course of inflammation showed a bimodal pattern with an early deposition of a filamentous material with a band pattern, typical of fibrin. Despite a fluid-filled middle ear cavity, the inflammatory changes in the otitis media with effusion model were moderate, as was consistent with the clinical appearance of the tympanic membrane.

Acute Disease↗

Obese Zucker rats have reduced mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 1 expression in hippocampus-implications for dysregulation of the hypothalamic-pituitary-adrenal axis in obesity.

Obese Zucker rats have elevated basal corticosterone levels and an increased stress response suggestive of an increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesized that altered central expression of glucocorticoid receptors (GR), mineralocorticoid receptors (MR), and/or 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) contribute to these changes. In brains from young adult male rats, in situ hybridization and Western blotting showed that obese rats had normal hippocampal GR mRNA and protein levels. In contrast, in obese rats, 11betaHSD1 mRNA levels were reduced in a subpopulation of hippocampal cells in the main neuronal layers (by 37-47%, P < 0.05), whereas 11betaHSD1 levels in sparse high-expressing cells did not differ. MR mRNA was decreased in all regions of the hippocampus (by 37-49%, P < 0.05 for CA1-2 and P < 0.01 for dentate gyrus) and in frontal cortex (by 16%, P < 0.05) in obese rats. In whole hippocampal homogenates, however, neither the protein concentration of MR by Western blot nor activity of 11betaHSD1 was measurably different between the phenotypes. To test the functional importance of lower central MR expression, groups of lean and obese rats were given spironolactone before restraint stress. In vehicle-treated animals, obese rats had higher plasma corticosterone levels than lean rats after stress (by ANOVA, P < 0.05). Spironolactone markedly increased the corticosterone response in both groups, but the incremental rise was smaller in the obese rats, so that spironolactone abolished the differences between groups. We conclude that lower levels of MR, but not GR, contribute to the increased HPA activity in the obese Zucker rats and that this seems more influential during stress than in the basal state. This may be exacerbated by impaired local regeneration of corticosterone by 11betaHSD1. These abnormalities could contribute to the subtle changes in the HPA axis in rodent and human obesity.

11-beta-Hydroxysteroid Dehydrogenases↗

Myringotomized tympanic membranes cultured in vitro do not develop myringosclerosis.

The aim of this study was to evaluate the development of myringosclerosis in in vitro-cultured tympanic membranes. Sprague-Dawley rats were myringotomized bilaterally and the tympanic membranes were excised after sacrifice. The explants were placed in inserts in wells filled with a nutrient medium. Every second day the tympanic membranes were photodocumented and after 9 days the explants were prepared for histology. On the 4th day the explants had attached to the bottom of the inserts and the specimens had thickened. From the perforation borders and the dissection edges a thin outgrowth was extending across the surface. By Day 9 the perforation had clearly diminished in size when examined in a stereomicroscope. In a light microscope the keratin layer was seen to protrude towards the centre of the perforation and, at the borders, epithelial cells were bridging the gap. Neither the pars tensa nor the pars flaccida showed any sclerotic lesions. The pars flaccida had thickened and the basal cells of the outer keratinized epithelium had invaded the connective tissue. Inflammatory cells were sparse in both the pars tensa and pars flaccida. The in vitro-cultured myringotomized tympanic membrane therefore shows a similar healing pattern to that in vivo. However, inflammatory reactions are sparse and there is no development of myringosclerosis.

Animals↗