| 1. |
- Kågedal, Bertil, 1943-, et al.
(författare)
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Pterin-dependent tyrosine hydroxylase mRNA is not expressed in human melanocytes or melanoma cells
- 2004
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Ingår i: Pigment Cell Research. - : Wiley. - 0893-5785 .- 1600-0749. ; 17:4, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Pterin-dependent tyrosine hydroxylase has been described to occur occasionally in melanocytes. It is therefore important to quantify the mRNA of this enzyme in pigment cells to understand whether this enzyme can take an active part in pigment formation. A real-time reverse transcription-polymerase chain reaction method was used to quantify tyrosine hydroxylase mRNA in melanocytes and melanoma cells. The calibrator was obtained by amplification of a segment of cDNA from tyrosine hydroxylase mRNA, which included the target thus allowing enumeration of the number of transcripts per cell. In melanocytes (n = 3), tyrosine hydroxylase mRNA ranged from non-detectable to 0.000492 transcripts/cell and in melanoma cells from non-detectable to 0.005340 transcripts/cell. In neuroblastoma cells, the median tyrosine hydroxylase mRNA number was 0.4 transcripts/cell (range 0.02-25 transcripts/cell). The amount of tyrosine hydroxylase mRNA in the pigment cells was far less than the mRNA concentrations of four melanocyte-specific proteins measured in the same melanocytes and melanoma cells. We conclude that on the average less than 1 of 1000 melanocytes and melanoma cells contains at least one tyrosine hydroxylase mRNA molecule. Consequently, in 999 of 1000 cells translation into the corresponding enzyme protein cannot occur because of the lack of an mRNA template. Thus, in these cells there is no pterin-dependent tyrosine hydroxylase that can contribute to pigment formation by producing priming amounts of L-dopa for proper function of tyrosinase.
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| 2. |
- Nord, Maria, et al.
(författare)
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Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
- 2017
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Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing. - 2169-9712 .- 2169-9720. ; 06:01
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Tidskriftsartikel (refereegranskat)abstract
- Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.
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| 3. |
- Nord, Maria, et al.
(författare)
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Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
- 2017
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Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing Inc. - 2169-9712 .- 2169-9720. ; 6:2, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
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| 4. |
- Träger, Chatarina, 1962-, et al.
(författare)
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Quantitative analysis of tyrosine hydroxylase mrna for sensitive detection of neuroblastoma cells in blood and bone marrow
- 2003
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 49:1, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sensitive monitoring of minimal residual disease may improve the treatment of neuroblastoma in children. To detect and monitor neuroblastoma cells in blood and bone marrow, we developed a quantitative method for the analysis of tyrosine hydroxylase mRNA. Methods: We used real-time reverse transcription-PCR. The calibrator was constructed from a segment of tyrosine hydroxylase mRNA that included the target. Blood and bone marrow samples from 24 children with neuroblastoma and 1 child with ganglioneuroma were analyzed. Controls were blood samples from the cords of 40 babies, from 58 children 6 months to 15 years of age, and from 34 healthy adults, as well as from 12 children with other diseases. Results: The detection limit was ~70 transcripts/mL. All 144 blood controls were below this limit. At diagnosis, blood tyrosine hydroxylase mRNA was higher in children with widespread disease (stage 4/4S, n = 6, range, 203-46 000 transcripts/mL) than in patients with localized disease (stages 1-3, n = 6, =83 transcripts/mL, P = 0.002). Bone marrow from all five children with localized disease had concentrations <72 transcripts/mL, whereas five of six stage 4 patients had increased concentrations (6000-8 000 000 transcripts/mL, P <0.05). In nine children in whom tyrosine hydroxylase mRNA was measured repeatedly, the results corresponded to the clinical course. Conclusion: Quantitative analysis of tyrosine hydroxylase mRNA in blood and bone marrow is reliable and easy to perform and may be used for upfront staging, prognostic assessment, and treatment monitoring of neuroblastoma.
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