| 1. |
- Francardo, Veronica, et al.
(författare)
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Chapter 22 - Rodent Models of Treatment-Related Complications in Parkinson Disease
- 2014. - 2nd
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Ingår i: Movement Disorders : Genetics and Models - Genetics and Models. - 9780124051959 ; , s. 373-386
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Bokkapitel (refereegranskat)abstract
- Dopamine replacement therapy effectively relieves the typical motor features of Parkinson disease (PD), but it can cause complications that limit its utility. Dyskinesia (abnormal involuntary movements) and motor fluctuations (abrupt changes in the patients' motor status) occur in most PD patients after a few years of 3,4-dihydroxyphenyl-. l-alanine (l-DOPA) pharmacotherapy. Animal models reproducing these motor complications can be obtained in mice and rats if the nigrostriatal dopamine pathway is severely damaged. Within the large arsenal of neurotoxic and genetic models of PD, rodents with unilateral 6-hydroxydopamine lesions have the best characteristics for the sake of modeling l-DOPA-induced dyskinesia. When treated chronically with high doses of l-DOPA, these rodent models may also display motor response alterations reminiscent of the wearing-off fluctuations that occur in PD patients. Because of research performed on these animal models, our understanding of the molecular and biochemical mechanisms of l-DOPA-induced dyskinesia has made great advances, and several pharmacological approaches to treatment have been recently identified and successfully tested in proof-of-concept trials in PD patients. It is now well recognized that dopaminergic therapies for PD also cause nonmotor fluctuations (e.g., abrupt changes in mood and cognitive performance) and impulse control disorders. Valid rodent models of these nonmotor complications need to be developed as an important tool for basic and translational research on the cognitive and psychiatric features of PD.
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| 2. |
- Lindgren, Hanna, et al.
(författare)
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Putaminal Upregulation of FosB/Delta FosB-Like Immunoreactivity in Parkinson's Disease Patients with Dyskinesia
- 2011
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 1:4, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Delta FosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson's disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and Delta FosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/Delta FosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/Delta FosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/Delta FosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/Delta FosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of Delta FosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.
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| 3. |
- Vierth, Inge, 1959-, et al.
(författare)
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Impact of higher road vehicle dimensions on modal split : An ex-post analysis for Sweden
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Road freight transport is responsible for a considerable amount of congestion, noise and various forms of air pollution and policy instruments that reduce these negative external effects are therefore on top of many policy-makers’ lists. One of the discussed initiatives to reduce these externalities is to increase the maximum permissible weight and length of vehicle combinations. There are however concerns that higher vehicle dimensions will reduce road transport cost per tonne-kilometre and therefore lead both to a modal shift and to induced demand for road transportation.The extent to which the introduction of longer and heavier road vehicles attracts freight from competing modes is therefore a crucial question. The purpose of this study is to provide empirical evidence on this matter, by analyzing how the modal split in Sweden has developed following the adoption of increases in the maximum permissible vehicle dimensions.In this study, we utilize official statistics on freight transport by road, rail and water covering the period 1985 to 2013. We first investigate the extent to which LHVs were adopted following the increases in vehicle dimensions in 1990 and 1993. We then construct time-series for the modal split both on the aggregate level and the commodity group-level and analyze the short- and long-run development. We show that the share of tonne-kilometres and vehicle-kilometres performed by trucks with a load capacity above 40 tonnes increased substantially in the 1990s, which mainly came at the expense of the vehicles with the lowest capacity. This shows the high degree of incorporation of LHVs in the Swedish vehicle fleet. Our analysis of the aggregate modal split shows that both the rail and water shares were decreasing from 1985 up until 1995, when the trend reversed for rail transportation. In 2000, rail had regained the market share it had in 1990 and continued to increase in the 2000. Water transportation kept on losing market shares throughout the period of study. The modal share for road transportation developed much in the opposite way. The road share increased steadily between 1985–1990 and continued this way during most of the 1990s, until it stabilized around 60–65 percent. We also show that road and rail have experienced increases in the level of tonne-kilometres since 1990, which implies that the falling rail share between 1990 and 1995 was driven by higher tonne-kilometer growth rates for road transportation than for rail transportation.Our aggregated freight statistics do not allow us to attribute the development of the modal split during this period of study to a particular event such as the increase in maximum weights in 1990 and 1993. In particular, it is not possible to trace out substitution patterns between the transport modes. The weight reforms are likely to have mattered for the modal development, but so are the economic recession in the early 1990s, the railway sector reforms of 1996 and other structural changes in the transport market. What we do document is the lack of breaks in modal split trends at the weight reforms in 1990 and 1993. On the contrary, the share of each mode is continuing its long-term development.
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| 4. |
- Vierth, Inge, 1959-, et al.
(författare)
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Vehicle weight, modal split, and emissions : an ex-post analysis for Sweden
- 2018
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- This study combines official statistics on freight transportation and emissions to present the long-run development of the use of longer and heavier road vehicles (LHVs), modal split, road freight efficiency, and GHG emissions and air pollution following the increase in the maximum permissible vehicle weight in Sweden in 1990 and 1993. We find that LHVs were quickly incorporated in the vehicle fleet and that road freight efficiency of the largest vehicles increased after the reforms. There was no discernable break in modal split trends as the modal share for road continued its long-run development. We show that road transportation contributes by far the most to emission costs. The composition of the emissions from road freight changed after the weight reforms, with an increasing share of GHG-emissions.
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| 5. |
- Vierth, Inge, 1959-, et al.
(författare)
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Vehicle weight, modal split, and emissions : an ex-post analysis for Sweden
- 2018
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Ingår i: Sustainable Freight Transport. - : MDPI. - 9783038974352 - 9783038974369 ; , s. 57-71
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Bokkapitel (refereegranskat)abstract
- This study combines official statistics on freight transportation and emissions to present the long-run development of the use of longer and heavier road vehicles (LHVs), modal split, road freight efficiency, and GHG emissions and air pollution following the increase in the maximum permissible vehicle weight in Sweden in 1990 and 1993. We find that LHVs were quickly incorporated in the vehicle fleet and that road freight efficiency of the largest vehicles increased after the reforms. There was no discernable break in modal split trends as the modal share for road continued its long-run development. We show that road transportation contributes by far the most to emission costs. The composition of the emissions from road freight changed after the weight reforms, with an increasing share of GHG-emissions.
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| 6. |
- Aleman, Soo, et al.
(författare)
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Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 46:9, s. 1118-1126
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed. Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.
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| 7. |
- Andersson, Lisa, et al.
(författare)
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Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 642-646
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Tidskriftsartikel (refereegranskat)abstract
- Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
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| 8. |
- Arja, Katriann, et al.
(författare)
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Synthesis and Characterization of Novel Fluoro-glycosylated Porphyrins that can be Utilized as Theranostic Agents
- 2018
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Ingår i: ChemistryOpen. - : Wiley-VCH Verlagsgesellschaft. - 2191-1363. ; 7:7, s. 495-503
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Tidskriftsartikel (refereegranskat)abstract
- Small molecules with modalities for a variety of imaging techniques as well as therapeutic activity are essential, as such molecules render opportunities to simultaneously conduct diagnosis and targeted therapy, so called theranostics. In this regard, glycoporphyrins have proven useful as theranostic agents towards cancer, as well as noncancerous conditions. Herein, the synthesis and characterization of heterobifunctional glycoconjugated porphyrins with two different sugar moieties, a common monosaccharide at three sites, and a 2-fluoro-2-deoxy glucose (FDG) moiety at the fourth site are presented. The fluoro-glycoconjugated porphyrins exhibit properties for multimodal imaging and photodynamic therapy, as well as specificity towards cancer cells. We foresee that our findings might aid in the chemical design of heterobifunctional glycoconjugated porphyrins that could be utilized as theranostic agents.
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