| 61. |
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| 62. |
- Orhan, F, et al.
(författare)
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CSF GABA is reduced in first-episode psychosis and associates to symptom severity
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 23:5, s. 1244-1250
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.
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| 63. |
- Orhan, F., et al.
(författare)
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Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis
- 2018
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Ingår i: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 138:5, s. 432-440
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
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| 64. |
- Pettersson-Klein, A. T., et al.
(författare)
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Small molecule PGC-1 alpha 1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration
- 2018
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 9, s. 28-42
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The peroxisome proliferator-activated receptor-gamma coactivator-1 alpha 1 (PGC-1 alpha 1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1 alpha 1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1 alpha 1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1 alpha 1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1 alpha 1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions.Methods: We designed a cell-based high-throughput screening system to identify PGC-1 alpha 1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1 alpha 1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes.Results: Among 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1 alpha 1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes.Conclusions: We identify compounds that induce PGC-1 alpha 1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders.
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| 65. |
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| 66. |
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| 67. |
- Plos, M., et al.
(författare)
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Non-Linear Analysis and Remaining Fatigue Life of Reinforced Concrete Bridges
- 2007
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Rapport (refereegranskat)abstract
- The work provides methods for non-linear structural analysis and fatigue safety evaluation in assessment of existing railway bridges. The use of non-linear analysis leads to higher load carrying capacities, but also to improved understanding of the structural response, forming a better basis for decisions in the assessment. The methods for fatigue assessment lead to increased remaining service life of reinforced concrete railway bridges.The achievements of the work are:• Models for assessment of concrete bridges by non-linear analysis are described, and examples and general recommendations for practical application of the methods aregiven.• An overview of the effect of corrosion on the bond properties has been developed through non-linear analyses and tests found in literature. Recommendations for practical assessment of anchorage capacity in corroded railway concrete bridges are presented.• The determination of reliable in-situ material properties in old concrete bridges is described,including properties for fully probabilistic analysis. A particular aim was to develop better methods to describe development of concrete properties with age and degree of hydration.• Recommendations are given regarding re-distribution of sectional forces and moments, obtained through linear structural analysis (with FEM). In a case study, a typical slab bridge was designed using different methods, and its response evaluated through nonlinearanalyses.• A good understanding of the load-carrying mechanisms in combined bending-shear-torsion gives a possibility to make more accurate assessments than with standard code methods. Methods and examples are presented.• A state-of-the-art review of fatigue behaviour of reinforced concrete railway bridges is presented and a methodology to assess the remaining fatigue life of existing reinforced concrete bridges subjected to railway traffic is developed.
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| 68. |
- Plos, Mario, et al.
(författare)
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Structural assessment of railway concrete bridges : non-linear analysis and remaining fatigue life
- 2006
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Ingår i: Bridge Maintenance, Safety, Management, Life-Cycle Performance and Cost. - London : Taylor and Francis Group. - 0415403154 ; , s. 271-
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Konferensbidrag (refereegranskat)abstract
- For a sustainable development in Europe, there is a need to at least double the railway transports in the coming 20 years. In order to reach this, the residual service lives of existing concrete bridges need to be extended at the same time as they are subjected to higher axle loads, higher railway speeds and heavier traffic intensity. Today, many concrete bridges are replaced or strengthened because their reliability cannot be guaranteed based on the structural assessments made. The aim of the work presented here is to provide enhanced assessment methods that are able to prove higher load carrying capacities and longer fatigue lives for existing concrete railway bridges. One main objective is to facilitate the use of non-linear analysis for structural assessment. In addition to higher load carrying capacities, the methods give improved understanding of the structural response, forming a better basis for decisions in the assessment. Another main objective is to improve knowledge about the fatigue behaviour of concrete bridges and to develop realistic methods for the evaluation of remaining fatigue life of existing bridges. The emphasis here is on short-span bridges and secondary elements. The work presented is a part of the ongoing EU-project Sustainable Bridges. The results will be implemented in the Guideline for Load and Resistance Assessment of existing European Railway Bridges that is being developed
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| 69. |
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