| 1. |
- Bengtsson, Sara K. S., et al.
(författare)
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Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans
- 2015
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 52, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.
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| 2. |
- Bäckström, Torbjörn, 1948-, et al.
(författare)
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Pathogenesis in menstrual cycle-linked CNS disorders.
- 2003
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1007, s. 42-53
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Fjellstrom, Sanna, et al.
(författare)
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Web-based training intervention to increase physical activity level and improve health for adults with intellectual disability
- 2022
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Ingår i: Journal of Intellectual Disability Research. - : John Wiley & Sons. - 0964-2633 .- 1365-2788. ; 66:12, s. 967-977
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individuals with intellectual disability (ID) are less physically active, have a higher body mass index (BMI) and are at greater risk for cardiovascular diseases (CVDs) than people without ID. The purpose of the study was to explore the effectiveness of a web-based training programme, consisting of 150 min of activity per week, on the health of people with ID.Method: Participants with ID living in supported accommodation (n = 28, 48% female, age = 36.4 ± 9.56 years) participated in a web-based training programme, consisting of a combination of exercises (endurance, strength balance and flexibility) of moderate intensity, 50 min, three times per week for 12 weeks. The body composition and waist circumference (WC) were measured, and questionnaires were used to assess enjoyment, quality of life (QoL) and physical activity (PA) level. Descriptive statistics and pairwise comparison pre and post intervention were carried out.Results: A total of 22 out of 28 participants completed the 12-week training intervention with 83% mean attendance of training sessions. The intensity of the PA level increased and a decrease in fat mass of 1.9 ± 2.4 kg, P < 0.001 and WC of 3 ± 5 cm, P = 0.009 were observed. Enjoyment of training sessions was 3.9 out of 5, and no differences in QoL were found.Conclusion: A web-based training programme is an effective tool for improving health parameters of people with ID and offers a new way for caregivers to enhance the PA for the target group.
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| 4. |
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| 5. |
- Hedström, Helena, et al.
(författare)
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Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women
- 2009
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 203:1, s. 85-98
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Tidskriftsartikel (refereegranskat)abstract
- Rationale The pharmacokinetics and behavioral effects of isoallopregnanolone (3β-hydoxy-5α-pregnan-20-one) in women are not known. Objectives Allopregnanolone (3α-hydoxy-5α-pregnan-20-one) is a well-known neurosteroid, acting via the GABAA receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3β-stereoisomer of allopregnanolone. Prior studies have concluded that isoallopregnanolone has no effect on the GABAA receptor. However, an antagonistic effect of isoallopregnanolone to allopregnanolone on the GABAA receptor has been shown in animal and in vitro studies. The purpose of this study was to evaluate the pharmacokinetics and behavioral effects of isoallopregnanolone in humans. Materials and methods Six healthy women were given three increasing doses of isoallopregnanolone intravenously in the follicular phase. Repeated blood samples for analyses of isoallopregnanolone and allopregnanolone concentrations were drawn. Saccadic eye movement variables, self-rated sedation, and mood rating scales were used during the test day. A Likert scale for prospective symptoms was used to measure daily fluctuations during the ongoing menstrual cycle. Results Exogenously administered isoallopregnanolone produced a dose-dependent increase in the serum concentration of isoallopregnanolone. In parallel, there was also a rise in the allopregnanolone concentration. There was a decrease in saccadic eye movement variables, but no effect was found on self-rated sedation or mood and no changes were seen in prospective symptoms during the menstrual cycle. Conclusions After administration of isoallopregnanolone at a cumulative dose of 0.20 mg/kg, no adverse effects were observed. There is a metabolism of isoallopregnanolone to allopregnanolone, most likely explaining the effects on the saccadic eye movements.
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| 6. |
- Lampe, Elisabeth O., et al.
(författare)
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Dissection of Francisella-Host Cell Interactions in Dictyostelium discoideum
- 2016
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 82:5, s. 1586-1598
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Tidskriftsartikel (refereegranskat)abstract
- Francisella bacteria cause severe disease in both vertebrates and invertebrates and include one of the most infectious human pathogens. Mammalian cell lines have mainly been used to study the mechanisms by which Francisella manipulates its host to replicate within a large variety of hosts and cell types, including macrophages. Here, we describe the establishment of a genetically and biochemically tractable infection model: the amoeba Dictyostelium discoideum combined with the fish pathogen Francisella noatunensis subsp. noatunensis. Phagocytosed F. noatunensis subsp. noatunensis interacts with the endosomal pathway and escapes further phagosomal maturation by translocating into the host cell cytosol. F. noatunensis subsp. noatunensis lacking IglC, a known virulence determinant required for Francisella intracellular replication, follows the normal phagosomal maturation and does not grow in Dictyostelium. The attenuation of the F. noatunensis subsp. noatunensis Delta iglC mutant was confirmed in a zebrafish embryo model, where growth of F. noatunensis subsp. noatunensis Delta iglC was restricted. In Dictyostelium, F. noatunensis subsp. noatunensis interacts with the autophagic machinery. The intracellular bacteria colocalize with autophagic markers, and when autophagy is impaired (Dictyostelium Delta atg1), F. noatunensis subsp. noatunensis accumulates within Dictyostelium cells. Altogether, the Dictyostelium-F. noatunensis subsp. noatunensis infection model recapitulates the course of infection described in other host systems. The genetic and biochemical tractability of the system allows new approaches to elucidate the dynamic interactions between pathogenic Francisella and its host organism.
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| 7. |
- Norberg, Eva-Britt, 1956-, et al.
(författare)
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Exploring reach and experiences of participation in health-promoting senior meetings in a municipality context
- 2021
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Ingår i: Journal of Public Health. - : Springer. - 2198-1833 .- 1613-2238. ; 29, s. 641-651
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore reach and experiences of participants during implementation of health-promoting meetings of seniors in a Swedish municipality context.Subjects and methods: A mixed-methods approach was used, including older people who were recruited consecutively and invited to participate as they applied for health care and/or home help services in the municipality. Inclusion criterion was allocation of “early” home-care services, e.g., meals on wheels, safety alarms. Health-care services were limited to persons applying for an outside walker. The intervention was multi-professional, e.g., occupational therapy and physiotherapy. Each session included a mix of short lectures and group discussions about, for example, the importance of engagement in meaningful activity, social contacts, and physical activity. Recruitment procedures were modified during the trial in order to enhance reach. The data collection included information on the flow of participants during recruitment and participation in the intervention, field notes covering the experience of implementing the intervention, a survey covering adherence to recruitment procedures, and qualitative interviews exploring the experience of participants.Results: Senior meetings were experienced as positive and strengthened the participants in dealing with health-related concerns. The identification of potential participants and recruitment were challenging, but as recruitment procedures were modified, a higher proportion of potential participants were reached. In all, there were 29 participants over the study period.Conclusion: For health-promoting meetings to enable community-dwelling older people to fulfill their potential by positively affecting health outcomes, recruitment procedures for optimizing reach is a critical feature.
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| 8. |
- Nyberg, Sigrid, et al.
(författare)
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Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome
- 2007
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Ingår i: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 23:5, s. 257-266
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurosteroids such as allopregnanolone and pregnanolone are suggested to be of importance for the pathophysiology of premenstrual dysphoric disorder. The aim of this study was to investigate whether the luteal-phase serum concentrations of these neurosteroids are associated with improvement of premenstrual symptoms in 12 women with severe premenstrual syndrome after treatment with low-dose gonadotropin-releasing hormone agonist and placebo. METHODS: Daily ratings for mood and physical symptoms were made prior to treatment and throughout the study. Serum progesterone, allopregnanolone and pregnanolone were assessed in the luteal phase (cycle day -9 to cycle day -1). Based on their symptom ratings, subjects were grouped as either buserelin responders (n = 6) or placebo responders (n = 6). RESULTS: Buserelin responders displayed decreased levels of allopregnanolone (p < 0.05) and progesterone (p < 0.05) in parallel with improvement of symptoms. During the placebo treatment, the placebo responders had lower serum allopregnanolone concentrations than buserelin responders (p < 0.05). This was associated with improvement in symptoms compared with pre-treatment ratings. CONCLUSION: Treatment response, whether induced by buserelin or placebo, appears to be associated with a decrease in allopregnanolone concentration.
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| 9. |
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| 10. |
- Turkmen, Sahruh, et al.
(författare)
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3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.
- 2004
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 20:6, s. 1604-1612
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Tidskriftsartikel (refereegranskat)abstract
- Allopregnanolone is a progesterone metabolite and GABA-A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3beta-hydroxypregnane steroids antagonize allopregnanolone-induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) as a blocker of allopregnanolone-induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2-hydroxypropyl-beta-cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone-injected group on day 6. Day 3-6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone-injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3-6), compared to the allopregnanolone-injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 micro m GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA-A receptor reduce the negative allopregnanolone effect on learning in the water maze.
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