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Folia Medica Dec 2023Parkinson's disease in its advanced stage is a progressive condition that can be treated with levodopa. The long-term complications of this treatment are difficult to...
Parkinson's disease in its advanced stage is a progressive condition that can be treated with levodopa. The long-term complications of this treatment are difficult to manage. A new device-aided therapy has recently been developed to minimize these effects.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Antiparkinson Agents; Drug Combinations; Catechols; Nitriles
PubMed: 38351782
DOI: 10.3897/folmed.65.e108196 -
Neurotoxicity Research Feb 2024Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most...
Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.
Topics: Humans; Cannabidiol; Neurotoxicity Syndromes; Neurons; Astrocytes; Carbidopa
PubMed: 38349488
DOI: 10.1007/s12640-024-00692-5 -
Clinical Neurology and Neurosurgery Feb 2024Abulia is a common problem that manifests following various brain conditions, including brain surgeries. Abulia is felt to be related to dysfunction with the brain's...
Abulia is a common problem that manifests following various brain conditions, including brain surgeries. Abulia is felt to be related to dysfunction with the brain's dopamine-dependent circuitry. The role of default mode network (DMN) in its pathogenesis is crucial. In this case report, we detail the presentation of abulia in an elderly woman following surgical resection of a right frontal glioblastoma involving the DMN. Connectomic imaging was used pre-operatively and post-operatively, demonstrating disruption of regions integral to the DMN and the central executive network. We observed a significant cognitive improvement following the administration of levodopa and carbidopa. Preoperative assessment of both anatomical and functional networks can help ensure surgical safety and predict postoperative deficits. This evaluation not only enhances preparedness and facilitates early case diagnosis but also expedites the initiation of prompt and potentially targeted treatments. This case highlights the potential efficacy of levodopa and carbidopa in addressing DMN dysfunction and broadly suggests the potential for connectomics-guided post-operative therapies.
Topics: Female; Humans; Aged; Connectome; Brain; Dopamine Agonists; Levodopa; Carbidopa; Magnetic Resonance Imaging; Cognition; Frontal Lobe
PubMed: 38340430
DOI: 10.1016/j.clineuro.2024.108145 -
Molecular Genetics and Metabolism Mar 2024Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal-recessive neurometabolic disorder caused by variants in dopa decarboxylase (DDC) gene,...
BACKGROUND
Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal-recessive neurometabolic disorder caused by variants in dopa decarboxylase (DDC) gene, resulting in a severe combined deficiency of serotonin, dopamine, norepinephrine, and epinephrine. Birth prevalence of AADCD varies by population. In pilot studies, 3-O-methyldopa (3-OMD) was shown to be a reliable biomarker for AADCD in high-throughput newborn screening (NBS) allowing an early diagnosis and access to gene therapy. To evaluate the usefulness of this method for routine NBS, 3-OMD screening results from the largest three German NBS centers were analyzed.
METHODS
A prospective, multicenter (n = 3) NBS pilot study evaluated screening for AADCD by quantifying 3-OMD in dried blood spots (DBS) using tandem mass spectrometry (MS/MS).
RESULTS
In total, 766,660 neonates were screened from January 2021 until June 2023 with 766,647 with unremarkable AADCD NBS (766,443 by 1st-tier analysis and 204 by 2nd-tier analysis) and 13 with positive NBS result recalled for confirmatory diagnostics (recall-rate about 1:59,000). Molecular genetic analysis confirmed AADCD (c.79C > T p.[Arg27Cys] in Exon 2 und c.215 A > C p.[His72Pro] in Exon 3) in one infant. Another individual was highly suspected with AADCD but died before confirmation (overall positive predictive value 0.15). False-positive results were caused by maternal L-Dopa use (n = 2) and prematurity (30th and 36th week of gestation, n = 2). However, in 63% (n = 7) the underlying etiology for false positive results remained unexplained. Estimated birth prevalence (95% confidence interval) was 1:766,660 (95% CI 1:775,194; 1:769,231) to 1:383,330 (95% CI 1:384,615; 1:383,142). The identified child remained asymptomatic until last follow up at the age of 9 months.
CONCLUSIONS
The proposed screening strategy with 3-OMD detection in DBS is feasible and effective to identify individuals with AADCD. The estimated birth prevalence supports earlier estimations and confirms AADCD as a very rare disorder. Pre-symptomatic identification by NBS allows a disease severity adapted drug support to diminish clinical complications until individuals are old enough for the application of the gene therapy.
Topics: Infant; Infant, Newborn; Child; Humans; Tandem Mass Spectrometry; Neonatal Screening; Pilot Projects; Prevalence; Prospective Studies; Amino Acid Metabolism, Inborn Errors; Aromatic-L-Amino-Acid Decarboxylases
PubMed: 38302374
DOI: 10.1016/j.ymgme.2024.108148 -
Journal of the Neurological Sciences Feb 2024Levodopa-carbidopa intestinal gel (LCIG) treatment markedly reduces motor fluctuations in patients with Parkinson's disease; however, some patients undergoing LCIG...
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) treatment markedly reduces motor fluctuations in patients with Parkinson's disease; however, some patients undergoing LCIG treatment may demonstrate clinical deterioration in the afternoon. Entacapone, a catechol-O-methyltransferase inhibitor, may be a promising adjunctive option for LCIG-treated patients; however, the optimal timing of oral entacapone administration to ameliorate clinical symptoms in the afternoon remains unexplored. This study aimed to investigate the optimal timing of oral entacapone administration in patients with Parkinson's disease undergoing LCIG treatment.
METHODS
Pharmacokinetic analysis and symptom assessment were performed on three days: a day without entacapone administration, day with oral entacapone administration at 13:00, and day with oral entacapone administration at 15:00.
RESULTS
Eight LCIG-treated patients were enrolled, of whom seven completed this study. The relative plasma concentrations of levodopa with entacapone administration at 13:00 were gradually increased, especially at 18:00 and were significantly higher than those without entacapone administration (127.10 ± 25.06% vs. 97.51 ± 22.20%). The relative plasma concentrations of 3-O-methyldopa were gradually increased without entacapone administration, whereas those with entacapone administration at 13:00 were lower than those without entacapone administration, especially at 17:00 (97.47 ± 3.70% vs. 110.71 ± 9.84%). Administering oral entacapone at 15:00 increased and decreased the relative plasma concentrations of levodopa and 3-O-methyldopa, respectively, but without significant difference. The "Off" time was shorter with entacapone administration at 13:00 (0.43 ± 0.79 h) and at 15:00 (0.57 ± 0.79 h) than that without entacapone administration (1.14 ± 1.46 h).
CONCLUSIONS
The concomitant use of oral entacapone in the early afternoon may be effective in improving afternoon symptoms in patients undergoing LCIG treatment.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Antiparkinson Agents; Catechol O-Methyltransferase; Drug Combinations; Catechols; Nitriles
PubMed: 38280299
DOI: 10.1016/j.jns.2024.122901 -
Retina (Philadelphia, Pa.) Feb 2024To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD).
PURPOSE
To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD).
METHODS
This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed.
RESULTS
Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g.
CONCLUSION
Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.
Topics: Humans; Diabetic Retinopathy; Angiogenesis Inhibitors; Case-Control Studies; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Metformin; Methyldopa
PubMed: 38259182
DOI: 10.1097/IAE.0000000000003968 -
Molecules (Basel, Switzerland) Jan 2024Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive... (Review)
Review
Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to the compound's pharmacological profile. CBD's role as a pharmacological inhibitor is explored, encompassing interactions with the endocannabinoid system and ion channels. The compound's anti-inflammatory effects, influencing the Interferon-beta and NF-κB, position it as a versatile candidate for immune system regulation and interventions in inflammatory processes. The historical context of Cannabis Sativa's use for recreational and medicinal purposes adds depth to the discussion, emphasizing CBD's emergence as a pivotal phytocannabinoid. As research continues, CBD's integration into clinical practice holds promise for revolutionizing treatment approaches and enhancing patient outcomes. The evolution in CBD research encourages ongoing exploration, offering the prospect of unlocking new therapeutic utility.
Topics: Humans; Cannabidiol; Biological Availability; Hallucinogens; Cannabinoid Receptor Agonists; Cannabis; Carbidopa
PubMed: 38257386
DOI: 10.3390/molecules29020473 -
Clinical Neurology and Neurosurgery Jan 2024Weight loss (WL) is the most common symptom among patients with Parkinson's disease (PD) and has been reported to start several years before the diagnosis of PD. The...
OBJECTIVE
Weight loss (WL) is the most common symptom among patients with Parkinson's disease (PD) and has been reported to start several years before the diagnosis of PD. The relationship between WL and PD treatment is complex. This study aimed to characterize the impact of PD treatment on WL and find clues to establish the administration of nutrition for patients with PD.
MATERIALS AND METHODS
Eighty-two patients with PD (mean age, 58.4 ± 10.2 years; mean Hoehn and Yahr stage, 3.2 ± 0.7) were recruited. Their treatments included deep brain stimulation (DBS) therapy (n = 34), levodopa/carbidopa intestinal gel (LCIG) therapy (n = 13), and oral medication alone (n = 35). Based on the medical records, the age of onset, disease duration, treatment options, videofluoroscopic dysphagia scale, blood test results, and weight change were collected.
RESULTS
The median WL per year and rate of WL were -1.0 ± 2.8 kg and -1.9 ± 4.7 %, respectively. Most patients (93 %) were classified into normal nutrition and mild malnutrition groups by their CONUT scores. The median WL of the DBS group was significantly lower than that of the oral medication alone group (p < 0.01). The rate of WL showed a significant negative correlation with the age of onset (rho = -0.328, p = 0.003), but showed a significant positive correlation with the disease duration (rho = 0.231, p = 0.04).
CONCLUSION
These results highlighted WL in the early stages of PD and suggested the need for adequate monitoring for patients undergoing device-aided therapy as well as oral medicine-treated patients with greater WL.
Topics: Humans; Middle Aged; Aged; Parkinson Disease; Antiparkinson Agents; Retrospective Studies; Levodopa; Carbidopa; Drug Combinations; Weight Loss; Gels
PubMed: 38194744
DOI: 10.1016/j.clineuro.2023.108105 -
Clinical Pharmacology in Drug... Apr 2024Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1...
Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1 study used a new immediate-release (IR) formulation of carbidopa/levodopa 25/100 mg that is functionally scored for easy and precise splitting to evaluate the effects on levodopa plasma variability when smaller doses are taken more frequently. These functionally scored tablets were shown to be bioequivalent to carbidopa/levodopa 25-/100-mg IR generic reference tablets. Twenty-two healthy volunteers received a whole tablet every 4 hours versus half of the tablet every 2 hours. Plasma levodopa fluctuations were significantly reduced with half-tablets dosed every 2 hours, with a 44% reduction in peaks (P < .0001). While drug exposure did not differ, parameters that underlie motor response variations, including mean peak-to-trough difference and variance, were 51% and 56% less, respectively, with more frequent dosing (both P ≤ .0024). Safety and tolerability of both regimens were similar. In conclusion, more frequent administration of half-tablets of the new functionally scored IR formulation safely provided more constant levodopa levels than whole tablets dosed less often. This tablet technology could facilitate the benefits of more physiologic dopamine replenishment in patients with PD, particularly those with reduced manual dexterity.
Topics: Humans; Levodopa; Carbidopa; Antiparkinson Agents; Cross-Over Studies; Parkinson Disease; Tablets
PubMed: 38176907
DOI: 10.1002/cpdd.1360 -
Pediatric Neurology Mar 2024Levodopa is used to treat hyperkinetic movements in children with dopa-responsive dystonia. However, levodopa may also be helpful in treating other forms of dystonia... (Review)
Review
BACKGROUND
Levodopa is used to treat hyperkinetic movements in children with dopa-responsive dystonia. However, levodopa may also be helpful in treating other forms of dystonia when used beyond a brief trial period.
METHODS
We performed a retrospective review of all children referred to our institution for evaluation of generalized dystonia and subsequently treated with carbidopa-levodopa. Motor function was assessed using video recordings and examination notes, quantified with the Burke-Fahn-Marsden Dystonia Rating Scale.
RESULTS
Long-term treatment with carbidopa-levodopa moderately improved motor function, whereas short-term use did not. Carbidopa-levodopa was well tolerated without untoward effects.
CONCLUSIONS
Dystonia is a significant cause of disability with limited effective treatment options. Published work is restricted but generally supports the findings of this review. A well-controlled study to examine the utility of carbidopa-levodopa treatment for dystonia is needed.
Topics: Child; Humans; Levodopa; Carbidopa; Dystonia; Dystonic Disorders; Treatment Outcome
PubMed: 38176223
DOI: 10.1016/j.pediatrneurol.2023.12.012