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- Fredriksson, Anders, et al.
(författare)
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Running wheel activity restores MPTP-induced functional deficits
- 2011
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Ingår i: Journal of neural transmission. - Wien : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 118:3, s. 407-420
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Tidskriftsartikel (refereegranskat)abstract
- Wheel-running and treadmill running physical exercise have been shown to alleviate parkinsonism in both laboratory and clinical studies. MPTP was administered to C57/BL6 mice using two different procedures: (a) administration of a double-dose regime (MPTP 2 × 20 or 2 × 40 mg/kg, separated by a 24-h interval), vehicle (saline 5 ml/kg) or saline (vehicle 2 × 5 ml/kg), and (b) administration of a single-dose weekly regime (MPTP 1 × 40 mg/kg) or saline (vehicle 1 × 5 ml/kg) repeated over 4 consecutive weeks. For each procedure, two different physical exercise regimes were followed: (a) after the double-dose MPTP regime, mice were given daily 30-min periods of wheel-running exercise over 5 consecutive days/week or placed in a cage in close proximity to the running wheels for 3 weeks. (b) Mice were either given wheel-running activity on 4 consecutive days (30-min periods) or placed in a cage nearby for 14 weeks. Behavioral testing was as follows: (a) after 3 weeks of exercise/no exercise, mice were tested for spontaneous motor activity (60 min) and subthreshold l-Dopa (5 mg/kg)-induced activity. (b) Spontaneous motor activity was measured on the fifth day during each of the each of the first 5 weeks (Tests 1–5), about 1 h before injections (first 4 weeks), and continued on the 5th days of the 6th to the 14th weeks (Tests 6–14). Subthreshold l-Dopa (5 mg/kg)-induced activity was tested on the 6th, 8th, 10th, 12th and 14th weeks. (b) Mice from the single-dose MPTP weekly regime were killed during the 15th week and striatal regions taken for dopamine analysis, whereas frontal and parietal cortex and hippocampus were taken for analysis of brain-derived neurotrophic factor (BDNF). It was shown that in both experiments, i.e., the double-dose regime and single-dose weekly regime of MPTP administration, physical activity attenuated markedly the MPTP-induced akinesia/hypokinesia in both the spontaneous motor activity and restored motor activity completely in subthreshold l-Dopa tests. Running wheel activity attenuated markedly the loss of dopamine due to repeated administrations of MPTP. BDNF protein level in the parietal cortex was elevated by the MPTP insult and increased further by physical exercise. Physical running wheel exercise alleviated both the functional and biomarker expressions of MPTP-induced parkinsonism.
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| 2. |
- Bergenholtz, Gunnar, 1939, et al.
(författare)
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Treatment of pulps in teeth affected by deep caries - A systematic review of the literature.
- 2013
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Ingår i: Singapore dental journal. - : World Scientific Pub Co Pte Lt. - 0377-5291. ; 34:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This systematic review assesses the effect of methods commonly used to manage the pulp in cases of deep caries lesions, and the extent the pulp chamber remains uninfected and does not cause pulpal or periapical inflammatory lesions and associated tooth-ache over time.STUDY DESIGN: An electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to March 2013. In addition, hand searches were carried out. Two reviewers independently evaluated abstracts and full-text articles. An article was read in full if at least one of the two reviewers considered the abstract potentially relevant. Altogether, 161 articles were read in full text. Of these, 24 studies fulfilled established inclusion criteria. Based on studies of at least moderate quality, the quality of evidence of each procedure was rated in four levels according to GRADE.RESULTS: No study reached the high quality level. Twelve were of moderate quality. The overall evidence was insufficient to assess which of indirect pulp capping, stepwise excavation, direct excavation and pulp capping/partial pulpotomy, pulpotomy or pulpectomy is the most effective treatment approach for teeth with deep caries.CONCLUSIONS: Because of the lack of good studies it is not possible to determine whether an injured pulp by deep caries can be maintained or whether it should be removed and replaced with a root canal filling. Both randomized studies and prospective observational studies are needed to investigate whether a pulp exposed to deep caries is best treated by measures intended to preserve it or by pulpectomy and root filling.
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| 5. |
- Bergman, Petra, et al.
(författare)
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Next-generation sequencing identifies microRNAs that associate with pathogenic autoimmune neuroinflammation in rats.
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:8, s. 4066-75
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are known to regulate most biological processes and have been found dysregulated in a variety of diseases, including multiple sclerosis (MS). In this study, we characterized miRNAs that associate with susceptibility to develop experimental autoimmune encephalomyelitis (EAE) in rats, a well-established animal model of MS. Using Illumina next-generation sequencing, we detected 544 miRNAs in the lymph nodes of EAE-susceptible Dark Agouti and EAE-resistant Piebald Virol Glaxo rats during immune activation. Forty-three miRNAs were found differentially expressed between the two strains, with 81% (35 out of 43) showing higher expression in the susceptible strain. Only 33% of tested miRNAs displayed differential expression in naive lymph nodes, suggesting that a majority of regulated miRNAs are EAE dependent. Further investigation of a selected six miRNAs indicates differences in cellular source and kinetics of expression. Several of the miRNAs, including miR-146a, miR-21, miR-181a, miR-223, and let-7, have previously been implicated in immune system regulation. Moreover, 77% (33 out of 43) of the miRNAs were associated with MS and other autoimmune diseases. Target genes likely regulated by the miRNAs were identified using computational predictions combined with whole-genome expression data. Differentially expressed miRNAs and their targets involve functions important for MS and EAE, such as immune cell migration through targeting genes like Cxcr3 and cellular maintenance and signaling by regulation of Prkcd and Stat1. In addition, we demonstrated that these three genes are direct targets of miR-181a. Our study highlights the impact of multiple miRNAs, displaying diverse kinetics and cellular sources, on development of pathogenic autoimmune inflammation.
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| 7. |
- Esbjörnsson, Joakim, et al.
(författare)
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Increased survival among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals
- 2014
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Ingår i: AIDS. - 1473-5571. ; 28:7, s. 949-957
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare survival times of HIV-1 single and HIV-1 and HIV-2 dual-infected individuals. Design: Prospective open cohort study. Methods: We analysed data from 259 HIV-1-seroincident cases (either HIV-1 single or HIV-1 and HIV-2 dual-infected) from a cohort with long follow-up (similar to 20 years) in order to study the influence of type of infection and infection order on mortality. Sex and age at HIV-1 infection date was controlled for in a Cox proportional-hazards model. Results: Dual-infected individuals had a 42% longer time from HIV-1 infection to death compared with single-infected individuals, adjusting for age asymmetries between groups. Dual-infected individuals with an HIV-2 infection preceding the HIV-1 infection had a more than two-fold lower mortality risk during follow-up than HIV-1 single-infected individuals. Conclusion: Survival time is longer and the risk of progression to death is lower among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals. This natural inhibition could have implications for the development of future HIV-1 vaccines and therapeutics.
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| 8. |
- Esbjörnsson, Joakim, et al.
(författare)
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Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:3, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. RESULTS: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. CONCLUSIONS: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).
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| 9. |
- Frisk, Fredrik, 1971, et al.
(författare)
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Pulp exposures in adults--choice of treatment among Swedish dentists.
- 2013
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Ingår i: Swedish dental journal. - : Swedish dental association. - 0347-9994. ; 37:3, s. 153-60
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Tidskriftsartikel (refereegranskat)abstract
- This study comprises a survey of Swedish dentists'treatment preferences in cases of carious exposure of the dental pulp in adults.The survey was conducted as part of a comprehensive report on methods of diagnosis and treatment in endodontics, published in 2010 by the Swedish Council on Health Technology Assessment. A questionnaire was mailed to a random subsample of 2012 dental offices where one dentist at each office was requested to answer all questions. Each questionnaire contained one of three sets of questions about endodontic practice routines.Thus around one-third of the subsample received case-specific questions about treating carious exposure. Only general practitioners aged below 70 years were included.The final study sample comprised 412 participants.The dentists were presented with two case scenarios. In Case 1 a 22-year old patient had a deep carious lesion in tooth 36 and in Case 2 a 50-year old patient had a deep carious lesion in tooth 14.The participants were asked to nominate their treatment of choice: pulp capping, partial pulpotomy or pulpectomy. For Case 1, 17 per cent of the respondents selected pulpectomy; the corresponding rate for Case 2 was 47 per cent. Female gender and age group 25-49 years were predictive of selection of less invasive treatment options. However, according to recent guidelines (2011) from the National Board of Health and Wellfare, Swedish dentists are recommended to elect pulpectomy prior to pulp capping/partial pulpotomy when confronted with a tooth having a cariously exposed pulp in adults.
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| 10. |
- Harbst, Katja, et al.
(författare)
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Molecular and genetic diversity in the metastatic process of melanoma.
- 2014
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
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