Parkinson\'s disease (PD) is a chronic neurodegenerative case. As the disease progresses, the response time to doses of levodopa (L-Dopa) becomes shorter and the effects of the drug are severely limited by some undesirable side effects such as the \'on-off\' phenomenon. In several diseases, including Parkinson\'s, nanoparticles can deliver antioxidant compounds that reduce oxidative stress. This study evaluates and compares the neuroprotective effects of L-Dopa-modified zinc nanoparticles (ZnNPs) in the 6-hydroxydopamine (6-OHDA)-induced PD rat model. For this purpose, the synthesis of NPs was carried out. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectrophotometer were used for characterization. The rats were randomized into 9 experimental groups: control, lesion group (6-OHDA), 6-OHDA + 5 mg/kg L-Dopa, 6-OHDA + 10 mg/kg L-Dopa, 6-OHDA + 20 mg/kg L-Dopa, 6-OHDA + 20 mg/kg ZnNPs, 6-OHDA + 40 mg/kg ZnNPs, 6-OHDA + 30 mg/kg ZnNPs + L-Dopa, and 6-OHDA + 60 mg/kg ZnNPs + L-Dopa. Behavioral tests were performed on all groups 14 days after treatment. Phosphatase and tensin homolog, Excitatory amino acid transporter 1/2, and Glutamine synthetase gene analyses were performed on brain samples taken immediately after the tests. In addition, histological and immunohistochemical methods were used to determine the general structure and properties of the tissues. We obtained important findings that L-Dopa-modified ZnNPs increased the activity of glutamate transporters. Our experiment showed that glutamate increases neuronal cell vitality and improves behavioral performance. Therefore, L-Dopa-modified ZnNPs can be used to prevent neurotoxicity. According to what we found, results show that L-Dopa-modified ZnNPs will lend to the effective avoidance and therapy of PD.

The current study presents the creation of a straightforward and sensitive sensor based on ZnO/Co3O4 nanocomposite modified screen-printed electrode (ZnO/Co3O4NC/SPE) for levodopa determination. At ZnO/Co3O4NC/SPE, an oxidative peak for levodopa solution in pH 6.0 phosphate buffer solution (PBS) were seen that were both more resolved and more enhanced. Levodopa was measured using differential pulse voltammetry (DPV), which showed an excellent linear range (0.001-800.0 μM) and detection limit (0.81 nM). The presence of interference did not affect the electrochemical response of levodopa at ZnO/Co3O4NC/SPE, demonstrating high selectivity. Levodopa in a real samples have been successfully detected using the manufactured sensor.

Boiled lotus rhizome discs (BLRDs), as common processed products of lotus rhizome, have gained increasing attention from consumers and food manufacturers. However, the blue pigment formed during boiling affects its appearance and reduces the appetite of BLRDs. In this study, the effects of polyphenols and iron contents on blue pigment formation in BLRDs in different regions and months were investigated. Results revealed that blue variation was more serious in March and April of the second year in Wuhan, and polyphenols and iron contents in these two months were significantly higher than those in other months. Then, UPLC and UV-Vis analysis showed that polyphenols causing the formation of blue pigment in BLRDs were L-dopa, gallocatechin, catechin, epigallocatechin, chlorogenic acid and epicatechin, among which L-dopa (52.450 mg/100 g in fresh lotus rhizome (FLR)) and gallocatechin (36.210 mg/100 g in FLR) possessed the greatest effect. Moreover, the ESI-Q-TOF-MS analysis of L-dopa-iron chelate and gallocatechin-iron chelate suggested that the blue pigment of BLRDs was mainly in the form of bis-complexes under boiling conditions. The study on formation mechanism of blue pigment in BLRDs can provide a reference for lotus rhizome processing.

Deposition of amyloid-β (Aβ) in the brain can impair neuronal function and contribute to cognitive decline in Alzheimer\'s disease (AD). Here, we found that dopamine and the dopamine precursor levodopa (also called l-DOPA) induced Aβ degradation in the brain. Chemogenetic approaches in mice revealed that the activation of dopamine release from ventral tegmental area (VTA) neurons increased the abundance and activity of the Aβ-degrading enzyme neprilysin and reduced the amount of Aβ deposits in the prefrontal cortex in a neprilysin-dependent manner. Aged mice had less dopamine and neprilysin in the anterior cortex, a decrease that was accentuated in AD model mice. Treating AD model mice with levodopa reduced Aβ deposition and improved cognitive function. These observations demonstrate that dopamine promotes brain region-specific, neprilysin-dependent degradation of Aβ, suggesting that dopamine-associated strategies have the potential to treat this aspect of AD pathology.

Parkinson\'s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid- induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination L-dopa, an amelioration in both motor and non-motor symptoms such as depression-like behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment with 6-shogaol and L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.

BACKGROUND: The ideal timing for initiating levodopa in newly diagnosed people with Parkinson\'s disease (PD) is uncertain due to limited data on the long-term effects of levodopa.
OBJECTIVE: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries.
METHODS: Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as \"early initiators\" (initiating levodopa within 2 years of diagnosis) or \"nonearly initiators.\" We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates.
RESULTS: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05).
CONCLUSIONS: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.

OBJECTIVE: We aimed to elicit scientific evidence on the cost-effectiveness of two catechol-O-methyltransferase inhibitors (COMT-i) versus no COMT-i in patients with advanced Parkinson\'s disease.
METHODS: A mixed model of the decision tree and a Markov model with three health states by OFF-time level (<25%, ≥25%, and death) was constructed to compare opicapone (OPC), entacapone (ENT), and no COMT-i over a lifetime. A hypothetical cohort of 10,000 patients was created and simulated based on the characteristics of the BIPARK trial subjects.
RESULTS: Two COMT-i (OPC and ENT) were identified as a cost-effective option compared to no COMT-i. Probabilistic sensitivity analysis showed that over 90% of the simulations proved the robust cost-effectiveness of COMT-i. When the time horizon as the most influential factor decreases to a 5- and 10-year period, COMT-i can be a cost-saving option. Although ENT may be the preferred option over OPC economically because of its lower price, OPC can be acceptable if the drug price is reduced by 17%.
CONCLUSIONS: Add-on treatment with COMT-i in patients with PD receiving levodopa/carbidopa appears to be cost-saving compared with not using COMT-i. In the future, it is necessary to evaluate the economic evaluation of COMT-i based on long-term real-world evidence.

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UNASSIGNED: To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson\'s disease (PD), with and without LID.
UNASSIGNED: We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson\'s Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum.
UNASSIGNED: The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without.
UNASSIGNED: Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.
UNASSIGNED: Comparar a densidade do transportador de dopamina (DAT) com outros fatores de risco para discinesia induzida pela L-DOPA em pacientes com doença de Parkinson, com e sem discinesias.
UNASSIGNED: Sessenta e sete sujeitos, 23 voluntários saudáveis e 44 pacientes pareados por idade com diferentes graus de gravidade da doença de Parkinson idiopática (29 homens; idade média ± desvio-padrão (DP), 59 ± 7 anos; duração média ± DP dos sintomas, 10 ± 6 anos; H&Y: média ± DP, 2,16 ± 0,65; UPDRS III: média ± DP, 29,74 ± 17,79). Todos os sujeitos realizaram SPECT cerebral com 99mTc-TRODAT-1. Além disso, foram calculadas as taxas de captação específica ou potenciais de ligação no estriado.
UNASSIGNED: A densidade de DAT do estriado ipsilateral ou contralateral foi menor no grupo doença de Parkinson. As variáveis duração da doença, dosagem de L-DOPA, doses por dia, tempo de duração do efeito da L-DOPA, H&Y e UPDRS III explicaram a ocorrência de discinesia. Adicionalmente, pacientes com discinesia exibiram menor densidade de DAT no estriado ipsilateral ou contralateral e no núcleo caudado do que os pacientes sem discinesia.
UNASSIGNED: O presente estudo sugere que a denervação dopaminérgica pré-sináptica na doença de Parkinson está associada ao desenvolvimento de discinesia induzida pela L-DOPA.

Herein, we report a 62-year-old female patient with Multiple system atrophy (MSA) at whom the sympathetic skin responses (SSRs) were absent at initial investigations. However, the levodopa therapy provided normalization of SSRs and moderately improvement in orthostatic hypotension-related symptoms. Based on this rare illustration, we discuss the possible mechanisms underlying the pathophysiology of autonomic dysfunction in MSA. We remark on the need for future clinical and experimental studies in this field.