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Tidsskrift For Den Norske Laegeforening... Nov 2018Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske... (Review)
Review
BAKGRUNN
Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske årsaksforhold har bedret forståelsen av sykdommene.
KUNNSKAPSGRUNNLAG
Artikkelen bygger på 39 artikler fra et systematisk søk i databasen Medline, to nettsteder og en lærebok.
RESULTATER
Doparesponsiv dystoni debuterer som oftest i barne- eller ungdomsårene og gir motoriske, kognitive, psykiatriske og/eller autonome symptomer og funn. Disse kan være uspesifikke og lett mistolkes som annen nevrologisk sykdom. Sykdommen skyldes feilkoding i ett enkelt gen og arves autosomalt recessivt eller dominant. Sykdomsgivende varianter er beskrevet fra tre ulike gener: guanosintrifosfat (GTP)-syklohydrolase-1-genet, sepiapterinreduktase-genet og tyrosinhydroksylase-genet. De sykdomsgivende variantene fører til enzymdefekt og gir tidlig debuterende dystoni, som responderer godt på levodopa. Nivåbestemmelse av pteriner, biogene monoaminer og deres metabolitter i spinalvæsken samt genetiske undersøkelser gir den eksakte diagnosen.
FORTOLKNING
Dagens kunnskap baserer seg på kasuistikker og mindre pasientmaterialer. Her fremgår det at pasientgruppen har stor nytte av levodopa. Diagnostikken har blitt enklere de siste årene med nyere biokjemiske og molekylærgenetiske analysemetoder. Basert på dagens litteratur er det grunn til å tro at vi har udiagnostiserte pasienter i Norge med doparesponsiv dystoni.
Topics: Adolescent; Age of Onset; Child; Diagnostic Errors; Dopamine Agents; Dystonic Disorders; Humans; Levodopa
PubMed: 30497245
DOI: 10.4045/tidsskr.17.0595 -
International Journal of Biological... Sep 2022Rifampicin has been previously described as an inhibitor of tyrosinase (Chai et al., Int. J. Biol. Macromol. 102 (2017) 425-430). However, rifampicin contains a...
Rifampicin has been previously described as an inhibitor of tyrosinase (Chai et al., Int. J. Biol. Macromol. 102 (2017) 425-430). However, rifampicin contains a p-diphenol group and compounds with such a moiety have been shown before to reduce tyrosinase-generated o-quinones. Rifampicin also shows strong absorption in a region completely overlapping with the visible absorption band of dopachrome, the oxidation product of L-tyrosine and L-dopa, whose concentration is measured spectrophotometrically in the standard enzymatic assay to monitor the activity of tyrosinase. We have demonstrated that rifampicin is also rapidly oxidized by o-quinones generated from catechols by tyrosinase or by treatment with sodium periodate. Smaller changes of absorbance at 475 nm during oxidation of L-dopa by tyrosinase in the presence of rifampicin do not result from enzyme inhibition but from oxidation of rifampicin by dopaquinone, which leads to rapid decrease of rifampicin absorption in this range. The actual reaction rates are not affected, which we have demonstrated by measurements of oxygen consumption. Rifampicin behaves therefore as other compounds with reducing properties, such as ascorbic acid, hydroquinone, hydrazine derivatives, and flavonoids, some of which have also been incorrectly described before as inhibitors of tyrosinase.
Topics: Kinetics; Levodopa; Monophenol Monooxygenase; Oxidation-Reduction; Rifampin; Tyrosine
PubMed: 35914550
DOI: 10.1016/j.ijbiomac.2022.07.217 -
Biomolecules Dec 2018Parkinson's disease is a movement disorder characterized by a progressive degeneration of dopaminergic neurons that has been object of study by the scientific community...
Parkinson's disease is a movement disorder characterized by a progressive degeneration of dopaminergic neurons that has been object of study by the scientific community through the last decades. However, nowadays there is still no treatment to cure it, although there are drugs available, with limited efficacy, to relieve the symptoms or replenish the cells with dopamine to supply the lack of dopaminergic neurons. This work was structured in two parts. In the first one, binary aqueous solutions of L-dopa and cyclodextrins were studied. In the second part, ternary aqueous solutions of L-dopa were studied with each of the selected cyclodextrins. In all cases, thermodynamic properties (density, partial molar volume and thermodynamic transfer functions for temperatures between 294.15 ± 0.01 K and 312.15 ± 0.01 K) and transport properties (mutual diffusion coefficients, viscosity, transfer viscosity at 298.15 ± 0.01 K and 310.15 ± 0.01 K) were studied. Using theoretical models to adjust the experimental data obtained for the diffusion coefficients and for the apparent molar volumes, in the ternary aqueous solutions, it was possible to estimate the values to the L-dopa-cyclodextrin association constant. For the aqueous ternary solutes, the partial molar volume of transfer of levodopa in the presence of the cyclodextrins, the partial molar expansibility at infinite dilution and from this, the Hepler constant, were determined. Also, the values of Gibbs free energy (Δ⁰), enthalpy (Δ⁰) and entropy (Δ⁰) were determined. From the obtained information, it was possible to characterize the molecular interactions, as well as to identify some structural characteristics of the controlled drug delivery systems under study and to estimate the influence of the cyclodextrin substituent groups, and, also, the temperature effect in the interaction levodopa-cyclodextrin. It is our intent to attain information about the mechanism of possible new systems for controlled drug delivery systems, throughout an alternative perspective, which could allow to increase its effectiveness in the Parkinson's treatment.
Topics: Cyclodextrins; Diffusion; Humans; Levodopa; Models, Theoretical; Parkinson Disease; Temperature; Thermodynamics; Viscosity
PubMed: 30583478
DOI: 10.3390/biom9010003 -
Journal of Parkinson's Disease 2023Oral levodopa is the gold-standard therapy for treating Parkinson's disease (PD) but after a few years of treatment the therapeutic window narrows, and patients often... (Review)
Review
Oral levodopa is the gold-standard therapy for treating Parkinson's disease (PD) but after a few years of treatment the therapeutic window narrows, and patients often experience various treatment-related complications. Patients in this advanced PD stage may benefit from alternative therapy, such as continuous intrajejunal delivery of levodopa-carbidopa intestinal gel (LCIG; or carbidopa-levodopa enteral suspension), continuous intrajejunal delivery of levodopa-carbidopa-entacapone intestinal gel, or continuous subcutaneous apomorphine infusion. Consideration and initiation of infusion therapies in advanced PD are suggested before the onset of major disability. The present review summarizes clinical evidence for infusion therapy in advanced PD management, discusses available screening tools for advanced PD, and provides considerations around optimal use of infusion therapy.
Topics: Humans; Parkinson Disease; Levodopa; Carbidopa; Antiparkinson Agents; Gels; Drug Combinations
PubMed: 37334617
DOI: 10.3233/JPD-225112 -
Movement Disorders : Official Journal... Jul 2021This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6,...
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society.
Topics: Genotype; Humans; Levodopa; Parkinson Disease; Parkinsonian Disorders; Phenotype
PubMed: 34396589
DOI: 10.1002/mds.28517 -
Journal of the Mechanical Behavior of... Dec 2022The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. In this study, we utilized L-DOPA as an interfacial agent for phosphate glass...
The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. In this study, we utilized L-DOPA as an interfacial agent for phosphate glass fibre/polycaprolactone (PGF/PCL) composites, with the aim to enhance the interfacial properties between the fibres and polymer matrix. The PGFs were dip-coated in varying concentrations of L-DOPA solution ranging between 5 and 40 g L. The fibre strength and interfacial shear strength (IFSS) of the composites were measured via a single fibre tensile test and single fibre fragmentation test, respectively. It was found that the L-DOPA agent (at conc. 10 g L) significantly improved the IFSS of the composites up to 27%. Also, the L-DOPA coating (at conc. 40 g L) significantly increased the glass fibre strength up to 18%. As a result, an optimum coating level could be tailored depending on application and whether fibre strength or IFSS was of greater importance. In addition, SEM and TGA analyses were used to detect and quantify the coating agents. FTIR and XPS further confirmed presence of the coating and indicated the zwitterionic crystals of L-DOPA and the formation of a melanin-like polymer layer. The spectroscopy data also evidenced that both catechol and amine groups contributed to the interaction between the L-DOPA and the PGF surface.
Topics: Phosphates; Levodopa; Biocompatible Materials; Polymers; Glass
PubMed: 36183666
DOI: 10.1016/j.jmbbm.2022.105480 -
Journal of Neural Transmission (Vienna,... Aug 2018With the advent of rodent models of L-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression... (Review)
Review
With the advent of rodent models of L-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.
Topics: Animals; Antiparkinson Agents; Brain; Dyskinesia, Drug-Induced; Levodopa; Neural Pathways
PubMed: 29704061
DOI: 10.1007/s00702-018-1886-0 -
FEBS Open Bio Apr 2019Melanin-producing and are highly invasive and can suppress or escape the immune system of the host. Since non-melanin-producing strains do not affect the immune...
Melanin-producing and are highly invasive and can suppress or escape the immune system of the host. Since non-melanin-producing strains do not affect the immune system, melanin may play a role in immune system suppression. Artificial melanin synthesized using conventional methods is insoluble, making structural and functional analysis of this chemical difficult. In this study, we describe a melanin solubilization method based on polymerization of homogentisic acid (solubilizing component) and an equivalent amount of L-DOPA in the presence of laccase. In addition, we investigated the effect of melanin on the immune system. Homogentisic acid and L-DOPA mixed melanin (HALD), the synthetic solubilized melanin, did not exert a cytotoxic effect on mouse macrophages. HALD suppressed cytokine and reactive oxygen species production by macrophages when they were stimulated by fungal components. HALD also suppressed the phagocytosis of fungal components by macrophages. These results suggest that HALD can suppress the function of macrophages without causing cytotoxicity.
Topics: Animals; Biochemistry; Homogentisic Acid; Laccase; Levodopa; Macrophages; Male; Melanins; Mice; Mice, Inbred C57BL; Polymerization; Solubility
PubMed: 30984552
DOI: 10.1002/2211-5463.12615 -
Current Opinion in Neurobiology Feb 2024L-DOPA-induced dyskinesia (LID) is the most common form of hyperkinetic movement disorder resulting from altered information processing in the cortico-basal ganglia... (Review)
Review
L-DOPA-induced dyskinesia (LID) is the most common form of hyperkinetic movement disorder resulting from altered information processing in the cortico-basal ganglia network. We here review recent advances clarifying the altered interplay between striatal output pathways in this movement disorder. We also review studies revealing structural and synaptic changes to the striatal microcircuitry and altered cortico-striatal activity dynamics in LID. We furthermore highlight the recent progress made in understanding the involvement of cerebellar and brain stem nuclei. These recent developments illustrate that dyskinesia research continues to provide key insights into cellular and circuit-level plasticity within the cortico-basal ganglia network and its interconnected brain regions.
Topics: Humans; Dyskinesia, Drug-Induced; Levodopa; Basal Ganglia; Corpus Striatum; Brain
PubMed: 38184982
DOI: 10.1016/j.conb.2023.102833 -
Journal of Proteome Research Jun 2023Post-translational modifications (PTMs) alter the function and fate of proteins and cells in almost every conceivable way. Protein modifications can occur as a result of...
Post-translational modifications (PTMs) alter the function and fate of proteins and cells in almost every conceivable way. Protein modifications can occur as a result of specific regulating actions of enzymes, such as tyrosine kinases phosphorylating tyrosine residues or by nonenzymatic reactions, such as oxidation related to oxidative stress and diseases. While many studies have addressed the multisite, dynamic, and network-like properties of PTMs, only little is known of the interplay of the same site modifications. In this work, we studied the enzymatic phosphorylation of oxidized tyrosine (l-DOPA) residues using synthetic insulin receptor peptides, in which tyrosine residues were replaced with l-DOPA. The phosphorylated peptides were identified by liquid chromatography-high-resolution mass spectrometry and the site of phosphorylation by tandem mass spectrometry. The results clearly show that the oxidized tyrosine residues are phosphorylated, displaying a specific immonium ion peak in the MS spectra. Furthermore, we detected this modification in our reanalysis (MassIVE ID: MSV000090106) of published bottom-up phosphoproteomics data. The modification, where both oxidation and phosphorylation take place at the same amino acid, has not yet been published in PTM databases. Our data indicate that there can be multiple PTMs that do not exclude each other at the same modification site.
Topics: Phosphorylation; Tyrosine; Levodopa; Peptides; Tandem Mass Spectrometry; Protein Processing, Post-Translational
PubMed: 37146082
DOI: 10.1021/acs.jproteome.3c00061