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Expert Opinion on Pharmacotherapy Dec 2020Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in...
INTRODUCTION
Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in the substantia nigra. Unfortunately, there is no curative treatment yet. The gold-standard of the treatment is levodopa (LD). During the course of the disease, motor complications develop, which postulates the addition of entacapone (ENT) to the dopaminergic medication. Previous studies have suggested that patients have a better quality of life when entacapone is added in a combination with LD.
AREAS COVERED
A systematic literature search was performed. Articles were identified through PubMed (MEDLINE), Web of Science, Ovid, and ClinicalTrials.gov databases. The following search terms were used: 'Levodopa' AND 'Carbidopa' OR 'Benserazide' AND 'Entacapone'. The search period was between 2000 and 2020. Twenty randomized and 10 non-randomized clinical trials (12,893 subjects) were included in the qualitative analysis. The systematic review was written in line with the PRISMA guideline.
EXPERT OPINION
ENT administered in combination with LD resulted in a better quality of life compared to separate tablets. Therefore, in PD patients where impaired motor performance develops and the application of entacapone is necessary, it is suggested to be administered in a single tablet form.
Topics: Antiparkinson Agents; Catechols; Drug Combinations; Humans; Levodopa; Motor Activity; Nitriles; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Tablets
PubMed: 32808807
DOI: 10.1080/14656566.2020.1806237 -
Frontiers in Neurology 2020Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra...
Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra (SN). There is also an increase in iron content in the SN in postmortem and imaging studies using iron-sensitive MRI techniques. However, MRI results are variable across studies. We performed a systematic meta-analysis of SN iron imaging studies in PD to better understand the role of iron-sensitive MRI quantification to distinguish patients from healthy controls. We also studied the factors that may influence iron quantification and analyzed the correlations between demographic and clinical data and iron load. We searched PubMed and ScienceDirect databases (from January 1994 to December 2019) for studies that analyzed iron load in the SN of PD patients using T2, R2, susceptibility weighting imaging (SWI), or quantitative susceptibility mapping (QSM) and compared the values with healthy controls. Details for each study regarding participants, imaging methods, and results were extracted. The effect size and confidence interval (CI) of 95% were calculated for each study as well as the pooled weighted effect size for each marker over studies. Hence, the correlations between technical and clinical metrics with iron load were analyzed. Forty-six articles fulfilled the inclusion criteria including 27 for T2/R2 measures, 10 for SWI, and 17 for QSM (3,135 patients and 1,675 controls). Eight of the articles analyzed both R2 and QSM. A notable effect size was found in the SN in PD for R2 increase (effect size: 0.84, 95% CI: 0.60 to 1.08), for SWI measurements (1.14, 95% CI: 0.54 to 1.73), and for QSM increase (1.13, 95% CI: 0.86 to 1.39). Correlations between imaging measures and Unified Parkinson's Disease Rating Scale (UPDRS) scores were mostly observed for QSM. The consistent increase in MRI measures of iron content in PD across the literature using R2, SWI, or QSM techniques confirmed that these measurements provided reliable markers of iron content in PD. Several of these measurements correlated with the severity of motor symptoms. Lastly, QSM appeared more robust and reproducible than R2 and more suited to multicenter studies.
PubMed: 32547468
DOI: 10.3389/fneur.2020.00366 -
Alcohol and Alcoholism (Oxford,... Feb 2021The appetite regulating hormone leptin, which is mainly secreted from adipose tissue, is an important regulator of food intake and modulator of reward-driven behavior....
AIMS
The appetite regulating hormone leptin, which is mainly secreted from adipose tissue, is an important regulator of food intake and modulator of reward-driven behavior. Leptin exerts its biological actions via binding to the leptin receptor, which is expressed in the hypothalamus, but also in the hippocampus, the amygdala and the substantia nigra. In the ventral tegmental area (VTA), leptin attenuates the firing rate of dopaminergic neurons that project to the Nucleus accumbens (NAc), which serves as relay to other brain areas of the "addiction network", such as the prefrontal cortex. This suggests that leptin plays a role in the processing of rewards in the context of substance use disorders such as alcohol use disorder, especially through attenuation of dopaminergic activity in the mesolimbic reward system. This supports the plausibility of leptin's potential effects in alcohol use disorder.
METHODS
We searched MEDLINE from 1990 to February 2020. All abstracts were screened for relevance and we only included publications reporting original data with a full text available in English language. Studies that did not report leptin-data, reviews or case reports/series were not included.
RESULTS
We identified a total of N=293 studies of whom a total of N=55 preclinical and clinical studies met the specified criteria. N=40 studies investigated the effects of alcohol on leptin plasma levels, N=9 studies investigated the effects of leptin on alcohol craving and N=6 studies investigated the effects of leptin on relapse and alcohol consumption.
CONCLUSIONS
In this review of preclinical and clinical data, we assess the role of leptin in alcohol use and the development and maintenance of an alcohol use disorder, alcohol craving and relapse. Integrating the existing preclinical and clinical data on leptin may reveal new and innovative targets for the treatment of substance use disorders in the future.
Topics: Alcohol Drinking; Animals; Behavior, Addictive; Craving; Dopaminergic Neurons; Female; Humans; Leptin; Male; Mice; Nucleus Accumbens; Rats; Ventral Tegmental Area
PubMed: 32490525
DOI: 10.1093/alcalc/agaa044 -
Neurological Sciences : Official... May 2020Parkinson's disease (PD) is the second most prevalent neurodegenerative disease characterized by severe dyskinesia due to a progressive loss of dopaminergic neurons...
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease characterized by severe dyskinesia due to a progressive loss of dopaminergic neurons along the nigro-striatal pathway. The current focus of treatment is to relieve symptoms through administration of levodopa, such as L-3,4-dihydroxy phenylalanine replacement therapy, dopaminergic agonist administration, functional neurosurgery, and gene therapy, rather than preventing dopaminergic neuronal damage. Hence, the application and development of neuroprotective/disease modification strategies is absolutely necessary. Currently, stem cell therapy has been considered for PD treatment. As for the stem cells, mesenchymal stem cells (MSCs) seem to be the most promising. In this review, we analyze the mechanisms of action of MSCs in Parkinson's disease, including growth factor secretion, exocytosis, and attenuation of neuroinflammation. To determine efficacy and protect patients from possible adverse effects, ongoing rigorous and controlled studies of MSC treatment will be critical.
Topics: Animals; Brain; Clinical Trials as Topic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neurons; Parkinson Disease; Treatment Outcome
PubMed: 31919699
DOI: 10.1007/s10072-020-04240-9 -
Pediatric Research Jun 2020Antenatal corticosteroids (ACSs) are recommended to all women at risk for preterm delivery; currently, there is controversy about the subsequent long-term neurocognitive...
BACKGROUND
Antenatal corticosteroids (ACSs) are recommended to all women at risk for preterm delivery; currently, there is controversy about the subsequent long-term neurocognitive sequelae. This systematic review summarizes the long-term neurodevelopmental outcomes after ACS therapy in animal models.
METHODS
An electronic search strategy incorporating MeSH and keywords was performed using all known literature databases and in accordance with PRISMA guidance (PROSPERO CRD42019119663).
RESULTS
Of the 669 studies identified, eventually 64 were included. The majority of studies utilized dexamethasone at relative high dosages and primarily involved rodents. There was a high risk of bias, mostly due to lack of randomization, allocation concealment, and blinding. The main outcomes reported on was neuropathological, particularly glucocorticoid receptor expression and neuron densities, and neurobehavior. Overall there was an upregulation of glucocorticoid receptors with lower neuron densities and a dysregulation of the dopaminergic and serotonergic systems. This coincided with various adverse neurobehavioral outcomes.
CONCLUSIONS
In animal models, ACSs consistently lead to deleterious long-term neurocognitive effects. This may be due to the specific agents, i.e., dexamethasone, or the repetitive/higher total dosing used. ACS administration varied significantly between studies and there was a high risk of bias. Future research should be standardized in well-characterized models.
Topics: Animals; Behavior, Animal; Central Nervous System; Dexamethasone; Female; Glucocorticoids; Humans; Models, Animal; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects
PubMed: 31822018
DOI: 10.1038/s41390-019-0712-1 -
Psychiatry Research Nov 2019Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans.
OBJECTIVE
Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans.
METHOD
A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Cochrane Library, Insight and Gray literature (Google Scholar and the British Library) for studies published until August 2018. A search strategy was developed using the terms: "dopamine" and "ethanol" or ""alcohol"," and "positron-emission tomography" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched.
RESULTS
We found 293 studies. After reading titles and abstracts 235 were considered irrelevant, as they did not meet the inclusion criteria. For the reading of the full text, 50 studies were analyzed. Of these 41 were excluded with reasons by study design, patient population, intervention and outcomes. Nine studies were included in our qualitative synthesis. Four studies have resulted in a reduction in availability only at the D2 receptor in different brain regions. Concerning the D3 receptor alone only one study reported this finding and four studies reported a decrease in both receptors.
CONCLUSION
Changes in D2 receptors in several brain regions in human alcoholics were found in a systematic review.
Topics: Alcoholism; Dopamine; Dopaminergic Neurons; Humans; Positron-Emission Tomography; Receptors, Dopamine D2
PubMed: 31521841
DOI: 10.1016/j.psychres.2019.112542 -
Regenerative Medicine May 2019Cell-based therapies must achieve clinical efficacy and safety with reproducible and cost-effective manufacturing. This study addresses process development issues using...
Cell-based therapies must achieve clinical efficacy and safety with reproducible and cost-effective manufacturing. This study addresses process development issues using the exemplar of a human pluripotent stem cell-based dopaminergic neuron cell therapy product. Early identification and correction of risks to product safety and the manufacturing process reduces the expensive and time-consuming bridging studies later in development. A New Product Introduction map was used to determine the developmental requirements specific to the product. Systematic Risk Analysis is exemplified here. Expected current value-based prioritization guides decisions about the sequence of process studies and whether and if an early abandonment of further research is appropriate. The application of the three tools enabled prioritization of the development studies.
Topics: Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Dopaminergic Neurons; Humans; Neurodegenerative Diseases; Pluripotent Stem Cells; Risk Assessment
PubMed: 31210581
DOI: 10.2217/rme-2018-0081 -
Frontiers in Aging Neuroscience 2019Acupuncture has been reported to have significant effects, not only in alleviating impaired motor function, but also rescuing dopaminergic neuron deficits in rodent...
Acupuncture has been reported to have significant effects, not only in alleviating impaired motor function, but also rescuing dopaminergic neuron deficits in rodent models of Parkinson's disease (PD). However, a systemic analysis of these beneficial effects has yet to be performed. To evaluate the neuroprotective effect of acupuncture in animal models of PD. A literature search of the PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Research Information Service System, and Japan Society of Acupuncture and Moxibustion databases was performed to retrieve studies that investigated the effects of acupuncture on PD. The quality of each included study was evaluated using the 10-item checklist modified from the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies. RevMan version 5.3 (Foundation for Statistical Computing, Vienna, Austria) was used for meta-analysis. The 42 studies included scored between 2 and 7 points, with a mean score of 4.6. Outcome measures included tyrosine hydroxylase (TH) level and dopamine content. Meta-analysis results revealed statistically significant effects of acupuncture for increasing both TH levels (33.97 [95% CI 33.15-34.79]; < 0.00001) and dopamine content (4.23 [95% CI 3.53-4.92]; < 0.00001) compared with that observed in PD control groups. In addition, motor dysfunctions exhibited by model PD animals were also mitigated by acupuncture treatment. Although there were limitations in the number and quality of the included studies, results of this analysis suggest that acupuncture exerts a protective effect on dopaminergic neurons in rodent models of PD.
PubMed: 31139074
DOI: 10.3389/fnagi.2019.00102 -
Journal of Clinical Neuroscience :... Jul 2019Functional magnetic resonance imaging (fMRI) is a non-invasive imaging modality that enables the assessment of neural connectivity and oxygen utility of the brain using... (Meta-Analysis)
Meta-Analysis
Functional magnetic resonance imaging (fMRI) is a non-invasive imaging modality that enables the assessment of neural connectivity and oxygen utility of the brain using blood oxygen level dependent (BOLD) imaging sequence. Electroencephalography (EEG), on the other hands, looks at cortical electrical impulses of the brain thus detecting brainwave patterns during rest and thought processing. The combination of these two modalities is called fMRI with simultaneous EEG (fMRI-EEG), which has emerged as a new tool for experimental neuroscience assessments and has been applied clinically in many settings, most commonly in epilepsy cases. Recent advances in imaging has led to fMRI-EEG being utilized in behavioural studies which can help in giving an objective assessment of ambiguous cases and help in the assessment of response to treatment by providing a non-invasive biomarker of the disease processes. We aim to review the role and interpretation of fMRI-EEG in studies pertaining to psychiatric disorders and behavioral abnormalities.
Topics: Adult; Brain; Brain Mapping; Brain Waves; Dopaminergic Neurons; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Male; Oxygen; Rest
PubMed: 30955950
DOI: 10.1016/j.jocn.2019.03.054 -
Frontiers in Neurology 2019Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.
PubMed: 30733703
DOI: 10.3389/fneur.2019.00013