| 1. |
- Hansson, Caroline, 1981, et al.
(författare)
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Influence of ghrelin on the central serotonergic signaling system in mice
- 2014
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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| 2. |
- Johansson, Birgitta, 1957, et al.
(författare)
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Placebo-controlled cross-over study of the monoaminergic stabiliser (-)-OSU6162 in mental fatigue following stroke or traumatic brain injury
- 2012
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 24:5, s. 266-274
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Tidskriftsartikel (refereegranskat)abstract
- Objective Mental fatigue occurring after a stroke or traumatic brain injury (TBI) often results in difficulties returning to work and pursuing social activities. No effective treatment of this condition is available today. In this study, we have tested a novel pharmacological strategy using the monoaminergic stabiliser (-)-OSU6162. Methods (-)-OSU6162 was given orally for 4 weeks in doses increasing from 15 to 45 mg b.i.d. to 12 patients suffering from mental fatigue, following upon stroke (n?=?6) or TBI (n?=?6). (-)-OSU6162 was compared with placebo using a double-blind, randomised cross-over design. Patients included were well rehabilitated physically with no gross impairment in cognitive functions other than those related to the mental fatigue. Results (-)-OSU6162 caused a remarkable improvement in mental stamina, as evaluated by a self-assessment scale on mental fatigue. Statistical significance was reached on the primary endpoint (Mental Fatigue Scale). There was a trend towards improvement in the secondary endpoints processing speed and attention. Principal component analysis showed an overall positive treatment effect in 7 of 12 patients. Beneficial responses were seen already during the first few days of active drug treatment. Increasing dosage caused no further improvement. Adverse reactions consisted of short-lasting mild nausea and attenuated appetite. These side effects disappeared upon dose reduction. Conclusion The monoaminergic stabiliser (-)-OSU6162 offers promise as a candidate for treatment of mental fatigue after a stroke or TBI.
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| 3. |
- Karlsson, Henrik
(författare)
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Vården av de arbetsoförmögna : reumatikervårdens framväxt i den tidiga välfärdsstaten
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is about the development of care for the chronically ill, particularly rheumatics, from 1900 to 1960. Two aspects, economic support and medical care, are discussed regarding the efforts made by society to improve the situation for the chronically ill. The aim is to investigate the underlying motives for the care, and the interests of the state and the medical profession in the matter. The development of the care takes place in a historical context in which the state increased its responsibility for the social security of the citizens. Primarily this was seen in the creation of a social insurance system. There is a focus on the introduction of a national basic pensions scheme in 1913, which apart from giving old age pension would also give economic security to those who were struck with disablement. To reduce the costs for early retirement disability pensions, where rheumatics were the largest group, economic resources were set aside for the purpose of combating and curing disablement. As a consequence of this initiative, specialist care for rheumatics was built up within the framework of the basic pensions scheme. At the same time, doctors were arguing that the care for rheumatics should have been organised in the public health service. The dissertation follows the institutional development of specialist care for rheumatics up to the 1960s, when the National Social Insurance Board took over the pension board’s duties and powers, and the decision was taken to transfer the specialist care for rheumatics to the county councils. In the organisational development, the influence of the medical profession and medical science in the shaping of the work is discussed. In addition, other factors such as changes in the labour market, where the motive was to rehabilitate the sick so that they could work and be self-supporting, are put forward as an important explanation for the organisational structuring that the care of rheumatics underwent during the twentieth century. This meant that social work became an important complement to the medical care itself.
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| 4. |
- Karlsson-Lindahl, Linda, 1972, et al.
(författare)
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Heparanase affects food intake and regulates energy balance in mice.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
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| 5. |
- Karlsson, Magdalena, et al.
(författare)
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Meanings of existential uncertainty and certainty for people diagnosed with cancer and receiving palliative treatment : A life-world phenomenological study
- 2014
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Ingår i: BMC Palliative Care. - : BioMed Central (BMC). - 1472-684X. ; 13:28
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany people around the world are getting cancer and living longer with the disease. Thanks to improved treatment options in healthcare, patients diagnosed with advanced gastrointestinal cancer can increasingly live for longer. Living with cancer creates existential uncertainty, but what does this situation mean for the individual? The purpose of the study is to interpret meanings of existential uncertainty and certainty for people diagnosed with advanced gastrointestinal cancer and receiving palliative treatment.MethodsThis study is part of a larger project in which 7 men and 7 women aged between 49 and 79 participated in a study of information and communication for people with advanced gastrointestinal cancer. A total of 66 interviews were conducted with participants who were followed up over time. The narrative interviews were transcribed verbatim and the texts were analysed in three steps: naive reading, structural analysis and interpreted whole by utilizing a phenomenological life-world approach.ResultsThis study has identified different spheres in which people diagnosed with advanced gastrointestinal cancer vacillate between existential uncertainty and certainty: bodily changes, everyday situations, companionship with others, healthcare situations and the natural environment. Existing in the move between existential uncertainty and certainty appears to change people’s lives in a decisive manner. The interview transcripts reveal aspects that both create existential certainty and counteract uncertainty. They also reveal that participants appear to start reflecting on how the new and uncertain aspects of their lives will manifest themselves –a new experience that lays the foundation for development of knowledge, personal learning and growth.ConclusionsPeople diagnosed with advanced gastrointestinal cancer and receiving palliative care expressed thoughts about personal learning initiated by the struggle of living with an uncertain future despite their efforts to live in the present. Their personal learning was experienced through a changed life for themselves and having to confront their own pending death and develop self-insight regarding finality of life. Healthcare professionals can try to support people receiving palliative treatment for cancer by diversifying avenues for their personal growth, thus helping them manage their existential uncertainty and gravitate towards greater existential certainty.
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| 6. |
- Karlsson, Magdalena, et al.
(författare)
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Meanings of existential uncertainty and certainty for people diagnosed with cancer and receiving palliative treatment: a life-world phenomenological study
- 2014
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Ingår i: Bmc Palliative Care. - : Springer Science and Business Media LLC. - 1472-684X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many people around the world are getting cancer and living longer with the disease. Thanks to improved treatment options in healthcare, patients diagnosed with advanced gastrointestinal cancer can increasingly live for longer. Living with cancer creates existential uncertainty, but what does this situation mean for the individual? The purpose of the study is to interpret meanings of existential uncertainty and certainty for people diagnosed with advanced gastrointestinal cancer and receiving palliative treatment. Methods: This study is part of a larger project in which 7 men and 7 women aged between 49 and 79 participated in a study of information and communication for people with advanced gastrointestinal cancer. A total of 66 interviews were conducted with participants who were followed up over time. The narrative interviews were transcribed verbatim and the texts were analysed in three steps: naive reading, structural analysis and interpreted whole by utilizing a phenomenological life-world approach. Results: This study has identified different spheres in which people diagnosed with advanced gastrointestinal cancer vacillate between existential uncertainty and certainty: bodily changes, everyday situations, companionship with others, healthcare situations and the natural environment. Existing in the move between existential uncertainty and certainty appears to change people's lives in a decisive manner. The interview transcripts reveal aspects that both create existential certainty and counteract uncertainty. They also reveal that participants appear to start reflecting on how the new and uncertain aspects of their lives will manifest themselves - a new experience that lays the foundation for development of knowledge, personal learning and growth. Conclusions: People diagnosed with advanced gastrointestinal cancer and receiving palliative care expressed thoughts about personal learning initiated by the struggle of living with an uncertain future despite their efforts to live in the present. Their personal learning was experienced through a changed life for themselves and having to confront their own pending death and develop self-insight regarding finality of life. Healthcare professionals can try to support people receiving palliative treatment for cancer by diversifying avenues for their personal growth, thus helping them manage their existential uncertainty and gravitate towards greater existential certainty.
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| 7. |
- Wisniewska, Magdalena, et al.
(författare)
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Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:26, s. 18175-18188
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.
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