| 1. |
- Berg, Rand Wilcox Vanden, et al.
(författare)
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Brain tissue saving effects by single-dose intralesional administration of Neuroprotectin D1 on experimental focal penetrating brain injury in rats
- 2019
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Ingår i: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868 .- 1532-2653. ; 64, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI)is followed by a secondary inflammation in the brain. Neuroprotectin D1 (NPD1)is synthesized from docosahexaenoic acid (DHA)and has anti-inflammatory and antiapoptotic effects in experimental models of neurodegenerative disease and brain ischemia-reperfusion. It is not known whether intralesional administration of NPD1 ameliorates inflammation and cell death after severe TBI. We therefore investigated the effects of NPD1 following a severe form of focal penetrating TBI. A total of 30 male Sprague-Dawley rats weighing between 350 and 450 g were exposed to focal penetrating TBI or sham surgery. The rats were randomized to NPD1 treatment (50 ng intralesionally, immediately following TBI)or no treatment. The rats were sacrificed at 24 or 72 h. All subgroups consisted of 5 rats. Brains were removed, fresh frozen, cut in 14-µm coronal sections and subjected to Fluoro-Jade, TUNEL, MnSOD, 3-NT, COX-2, Ox-42 and NF-κB immuno-staining and lesion size analyses. NPD1 decreased the lesion area at 72 h compared to no treatment with a mean change 42% (NPD1 14.1 mm 2 ; no treatment 24.5 mm 2 )(p < 0.01). No difference was detected in markers for neuronal degeneration, apoptosis, anti-inflammatory or antioxidative enzymes, or immune cells. In conclusion, single-dose intralesional administration of NPD1 had brain tissue sparing effects after focal penetrating TBI, which may be beneficial in preventing brain tissue damage, making NPD1 a potential candidate for further clinical applications. Exact mechanisms of action could not be determined and it is possible that continuous or multiple administration regimens may increase efficacy in sequential preclinical studies.
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| 2. |
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| 3. |
- Høyer, Marie, et al.
(författare)
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Health-related quality of life among women with breast cancer : a population-based study
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:7, s. 1015-1026
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Tidskriftsartikel (refereegranskat)abstract
- Background: High incidence rates of breast cancer emphasize the importance of increased knowledge about the health-related quality of life (HRQoL) in this patient group. The aim of the present study was to describe and compare HRQoL among breast cancer patients shortly after diagnosis with normative data from the general population, and to investigate how clinical, demographic, and socio-economic factors and social support are associated with HRQoL. Material and methods:Participants were identified in a population-based Breast Cancer Quality Register in central Sweden. Of 1573 women newly diagnosed with breast cancer during a one-year period (2007 – 2008), 69% (n =1086) completed a questionnaire including the EORTC QLQ-C30, BR23 and the HADS.Results: Compared to age-adjusted normative data, breast cancer patients (mean age 62 years, range 25–94), especially younger women (<50 years), experienced clinically meaningful poorer HRQoL. Clinically significant levels of anxiety and depressive symptoms were found among 14% and 6% of the patients, respectively. Factors associated with more problems/symptoms among study participants included chemotherapy, lack of social support, sick leave and a poor financial situation. Adding socio-economic factors diminished the association between age and HRQoL (p > 0.05).Conclusion:Recently diagnosed breast cancer patients reported poorer HRQoL in several dimensions compared to normative data. In addition to clinical and demographic factors, an unfavorable socio-economic standing was associated with more problems/symptoms. The present findings emphasize the importance of taking a variety of factors into account when assessing HRQoL in the clinical setting.
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| 4. |
- Jadid, Kayvan Dehlaghi, et al.
(författare)
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COX-2 inhibition by diclofenac is associated with decreased apoptosis and lesion area after experimental focal penetrating traumatic brain injury in rats
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 10:July
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is followed by a secondary inflammation in the brain. The inflammatory response includes prostanoid synthesis by the inducible enzyme cyclooxygenase-2 (COX-2). Inhibition of COX-2 is associated with improved functional outcome in experimental TBI models, although central nervous system-specific effects are not fully understood. Animal studies report better outcomes in females than males. The exact mechanisms for this gender dichotomy remain unknown. In an initial study we reported increased COX-2 expression in male rats, compared to female, following experimental TBI. It is possible that COX-2 induction is directly associated with increased cell death after TBI. Therefore, we designed a sequential study to investigate the blocking of COX-2 specifically, using the established COX-2 inhibitor diclofenac. Male Sprague-Dawley rats weighing between 250 and 350 g were exposed to focal penetrating TBI and randomly selected for diclofenac treatment (5 ?g intralesionally, immediately following TBI) (n = 8), controls (n = 8), sham operation (n = 8), and normal (no manipulation) (n = 4). After 24 h, brains were removed, fresh frozen, cut into 14?m coronal sections and subjected to COX-2 immunofluorescence, Fluoro Jade, TUNEL, and lesion area analyses. Diclofenac treatment decreased TUNEL staining indicative of apoptosis with a mean change of 54% (p 0.05) and lesion area with a mean change of 55% (p 0.005). Neuronal degeneration measured by Fluoro Jade and COX-2 protein expression levels were not affected. In conclusion, COX-2 inhibition by diclofenac was associated with decreased apoptosis and lesion area after focal penetrating TBI and may be of interest for further studies of clinical applications.
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| 5. |
- Lidin, Erik, et al.
(författare)
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Hippocampal Expression of Cytochrome P450 1B1 in Penetrating Traumatic Brain Injury
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:2
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal dysfunction contributes to multiple traumatic brain injury sequala. Female rodents’ outcome is superior to male which has been ascribed the neuroprotective sex hormones 17β-estradiol and progesterone. Cytochrome P450 1B1 (CYP1B1) is an oxidative enzyme influencing the neuroinflammatory response by creating inflammatory mediators and metabolizing neuroprotective 17β-estradiol and progesterone. In this study, we aimed to describe hippocampal CYP1B1 mRNA expression, protein presence of CYP1B1 and its key redox partner Cytochrome P450 reductase (CPR) in both sexes, as well as the effect of penetrating traumatic brain injury (pTBI). A total 64 adult Sprague Dawley rats divided by sex received pTBI or sham-surgery and were assigned survival times of 1-, 3-, 5-or 7 days. CYP1B1 mRNA was quantified using in-situ hybridization and immunohistochemistry performed to verify protein colocalization. CYP1B1 mRNA expression was present in all subregions but greatest in CA2 irrespective of sex, survival time or intervention. At 3-, 5-and 7 days post-injury, expression in CA2 was reduced in male rats subjected to pTBI compared to sham-surgery. Females subjected to pTBI instead exhibited increased expression in all CA subregions 3 days post-injury, the only time point expression in CA2 was greater in females than in males. Immunohistochemical analysis confirmed neuronal CYP1B1 protein in all hippocampal subregions, while CPR was limited to CA1 and CA2. CYP1B1 mRNA is constitutively expressed in both sexes. In response to pTBI, females displayed a more urgent but brief regulatory response than males. This indicates there may be sex-dependent differences in CYP1B1 activity, possibly influencing inflammation and neuroprotection in pTBI.
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| 8. |
- Wixe, Torbjörn, et al.
(författare)
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A short designed semi-aromatic organic nanotube - synthesis, chiroptical characterization, and host properties.
- 2014
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Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539. ; 12:44, s. 8930-8941
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Tidskriftsartikel (refereegranskat)abstract
- The first generation of an organic nanotube based on the enantiomerically pure bicyclo[3.3.1]nonane framework is presented. The helical tube synthesised is the longest to date having its aromatic systems oriented parallel to the axis of propagation (length ∼26 Å and inner diameter ∼11 Å according to molecular dynamics simulations in chloroform). The synthesis of the tube, a heptamer, is based on a series of Friedländer condensations and the use of pyrido[3,2-d]pyrimidine units as masked 2-amino aldehydes, as a general means to propagate organic tubular structures and the introduction of a methoxy group for modification toward solubility and functionalization are described. The electronic CD spectra of the tube and molecular intermediates are correlated with theoretical spectra calculated with time-dependent density functional theory to characterize the chirality of the tube. Both experimental (NMR-titrations) and theoretical (molecular dynamics simulations) techniques are used to investigate the use of the tube as a receptor for the acetylcholine and guanidinium cations, respectively.
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| 9. |
- Wixe, Torbjörn, et al.
(författare)
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Synthesis of an Orthogonal Topological Analogue of Helicene.
- 2013
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 19:44, s. 14963-14969
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy reported, based on a series of repeating Friedländer condensations that utilize pyrido[3,2-d]pyrimidine moieties as protected amino aldehydes, allows for the facile access of higher generations of helical, tubular structures. As a result of the synthetic strategy, only a helical isomer of the pentamer is possible. The structure and absolute configuration of the pentamer were elucidated from a combination of NMR spectroscopic data, optical properties, X-ray structures, and by comparison of an experimental electronic circular dichroism spectrum to a calculated spectrum.
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