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- Ericson, Cecilia, et al.
(författare)
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Ex vivo gene delivery of GDNF using primary astrocytes transduced with a lentiviral vector provides neuroprotection in a rat model of Parkinson's disease.
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 22:11, s. 2755-2764
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are, as normal constituents of the brain, promising vehicles for ex vivo gene delivery to the central nervous system. In the present study, we have used a lentiviral vector encoding glial cell line-derived neurotrophic factor (GDNF) to transduce rat-derived primary astrocytes, in order to evaluate their potential for long-term transgene expression in vivo and neuroprotection in a rat model of Parkinson's disease. Following transplantation of GDNF-transduced astrocytes to the intact striatum, the level of released GDNF was 2.93 +/- 0.28 ng/mg tissue at 1 week post-grafting, reduced to 0.42 +/- 0.12 ng/mg tissue at 4 weeks, and thereafter was maintained at this level throughout the experiment (12 weeks; 0.53 +/- 0.068 ng/mg tissue). Similarly, grafting to the substantia nigra (SN) resulted in a significant overexpression of GDNF ( approximately 0.20 ng/mg tissue) at 1 week. Intact animals receiving transplants of GDNF-transduced astrocytes displayed an increased contralateral turning (5.39 +/- 1.19 turns/min) in the amphetamine-induced rotation test, which significantly correlated with the GDNF tissue levels measured in the striatum, indicating a stimulatory effect of GDNF on the dopaminergic function. Transplantation of GDNF-transduced astrocytes to the SN 1 week prior to an intrastriatal 6-hydroxydopamine lesion provided a significant protection of nigral tyrosine hydroxylase-positive cells. By contrast, when the cells were transplanted to the striatum, the level of released GDNF was not sufficient to rescue the striatal fibers and, hence, to protect the nigral dopaminergic neurons. Overall, our results suggest that genetically modified astrocytes expressing GDNF can provide neuroprotection in a rat model of Parkinson's disease following transplantation to the SN.
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| 2. |
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| 3. |
- Ericson, Cecilia
(författare)
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Astrocytes as Cellular Vehicles in Ex Vivo Gene Therapy Studies to the Rat Brain
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurodegenerative disorders are characterized by a progressive cell-death in the brain, and loss of different functions in the patient. Today, there are no cures for any of the various diseases. Parkinson's disease is a neurodegenerative disorder with a prevalence of 0.1% and the first symptoms usually start to appear between 50-60 years of age with rigidity, tremor, bradykinesia and postural abnormalities. Even though the reason for the development is not fully understood, the pathophysiology of the disease has been well documented. ?Sere is a progressive loss of dopamine-producing cells in substantia nigra in the midbrain, resulting in a significant decline of dopamine levels in the striatum and a disturbed motoric function. ?Se most common treatment today is oral intake of levodopa, the rate-limiting enzyme in the dopamine synthesis pathway, however the effects of the drug becomes limited over time and hence, there is a need for alternative therapy. Instead of using fetal human tissue for transplantation, with both logistical and ethical dilemmas, ex vivo gene therapy holds great promise for treatment of different neurodegenerative disorders. Ex vivo gene therapy is a combination of cell transplantation and genetic engineering, with the aim of restoring lost neurotransmitters, such as dopamine, or to transfer neurotrophic factors to stimulate cell survival in a damaged or injured brain. In the present thesis, I have genetically modified primary astrocytes of both rodent and human origin with lentiviral vectors in order to evaluate the potential of the cells to provide long-term transgene expression following transplantation to the rat brain. Astrocytes are a type of glial cells in the brain attributed various functions, and have been explored in several studies to be used as cellular vehicles in ex vivo gene delivery to the central nervous system. Compared to previous studies were astrocytes have been genetically modified in vitro using other viralbased vectors, I have shown in my work that lentivirally transduced astrocytes have the capacity to express the transgene product at significant levels for up to at least 12 weeks after grafting to the rat brain. However, before moving towards clinical trials using genetically modified astrocytes, the vector system has to be further developed in order to be able to regulate the transgene expression, even after the cells have been integrated within the host brain.
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| 4. |
- Jesus Esteves Barata, Terezinha, et al.
(författare)
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Comparasion of two minimally invasive methods on the longevity of glass ionomer cement restorations : short-term results of a pilot study
- 2008
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Ingår i: Journal of Applied Oral Science. - 1678-7757 .- 1678-7765. ; 16:2, s. 155-160
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the clinical performance of glass ionomer cement (GIC) restorations comparing two minimally invasive methods in permanent teeth after 12 months. Fifty pregnant women (second trimester of pregnancy), mean age 22 ± 5.30 years, were treated by two previously trained operators. The treatment approaches tested were: chemomechanical method (CarisolvTM; MediTeam) and atraumatic restorative treatment (ART). A split-mouth study design was used in which the two treatments were randomly placed in 50 matched pairs of permanent teeth. The chemomechanical method (CM) was the test group and the ART was the control group. The treatments were performed in Public Health Centers. The tested restorative material was a high-strength GIC (Ketac Molar; 3M/ESPE). The restorations were placed according to the ART guidelines. Two calibrated independent examiners evaluated the restorations in accordance with ART criteria. The inter-examiner kappa was 0.97. Data were analyzed using 95% confidence interval on the binomial distribution and Fisher's exact test at 5% significance level. In a 12-month follow-up, 86% of the restorations were evaluated. In the test group (CM), 100% (CI=93.3-100%) of the restorations were considered successful. In the control group (ART) 97.6% (CI=87.4-99.9%) of the restorations were considered successful and 2.4% unsuccessful (marginal defect >0.5 mm). There was no statistically significant difference between the 12-mounth success rate for both groups (Fisher's exact test: P=0.49) and between the two operators (Fisher's exact test: P=1.00). Both minimally invasive methods, chemomechanical method and ART, showed a similar clinical performance after 12 months of follow up. Key words: Clinical trials. Restorations. Glass ionomer cements. Atraumatic Restorative Treatment. chemomechanical method. Carisolv.
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