-
RSC Advances Jun 2021Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two... (Review)
Review
Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two key steps of melanogenesis: tyrosine's hydroxylation to dihydroxyphenylalanine (DOPA), and oxidation of the latter species to dopaquinone. Melanin guards against the destructive effects of ultraviolet radiation which is known to produce considerable pathological disorders such as skin cancer, among others. Moreover, the overproduction of melanin can create aesthetic problems along with serious disorders linked to hyperpigmented spots or patches on skin. Several skin-whitening products which reduce melanogenesis activity and alleviate hyperpigmentation are commercially available. A few of them, particularly those obtained from natural sources and that incorporate a phenolic scaffold, have been exploited in the cosmetic industry. In this context, synthetic tyrosinase inhibitors (TIs) with elevated efficacy and fewer side effects are direly needed in the pharmaceutical and cosmetic industries owing to their protective effect against pigmentation and dermatological disorders. Furthermore, the biological significance of the chromone skeleton and its associated medicinal and bioactive properties has drawn immense interest and inspired many researchers to design and develop novel anti-tyrosinase agents based on the flavonoid core (2-arylchromone). This review article is oriented to provide an insight and a deeper understanding of the tyrosinase inhibitory activity of an array of natural and bioinspired phenolic compounds with special emphasis on flavonoids to demonstrate how the position of ring substituents and their interaction with tyrosinase could be correlated with their effectiveness or lack thereof against inhibiting the enzyme.
PubMed: 35480807
DOI: 10.1039/d1ra03196a -
Frontiers in Aging Neuroscience 2022Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side... (Review)
Review
BACKGROUND
Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson's disease.
METHODS
We first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices.
RESULTS
Our review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark.
CONCLUSION
Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
PubMed: 35462692
DOI: 10.3389/fnagi.2022.807909 -
RSC Advances Feb 2022A review article has been published recently (, 2021, , 22159-22198) describing flavonoids as inhibitors of tyrosinase. However, many compounds included in this review...
Comment on "Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review" by R. Obaid, E. Mughal, N. Naeem, A. Sadiq, R. Alsantali, R. Jassas, Z. Moussa and S. Ahmed, , 2021, , 22159.
A review article has been published recently (, 2021, , 22159-22198) describing flavonoids as inhibitors of tyrosinase. However, many compounds included in this review have been previously shown to act as substrates of this enzymes or antioxidants reducing tyrosinase-generated -quinones. Products of their oxidation absorb light in a range different than dopachrome, the oxidation product of l-tyrosine or l-dopa, whose concentration is measured spectrophotometrically in the standard enzymatic assay to monitor the activity of this enzyme. This effect is interpreted as enzyme inhibition, which, in fact, is only apparent and results from inadequate methodology.
PubMed: 35425534
DOI: 10.1039/d1ra08162d -
International Journal of Environmental... Feb 2022Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults.
AIM
We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION.
METHODS
We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis.
RESULTS
Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA ( = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF ( = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA.
CONCLUSION
Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.
Topics: Adult; Humans; Levodopa; Memantine; Optic Neuropathy, Ischemic; Oxygen; Steroids; Visual Acuity
PubMed: 35270411
DOI: 10.3390/ijerph19052718 -
Journal of Parkinson's Disease 2022Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy.
OBJECTIVE
We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa.
METHODS
We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups.
RESULTS
Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments.
CONCLUSION
Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35180134
DOI: 10.3233/JPD-213057 -
Movement Disorders Clinical Practice Feb 2022The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor... (Review)
Review
BACKGROUND
The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson's disease (PD) is lacking.
OBJECTIVE
To address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS.
METHODS
We used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted.
RESULTS
The STN-DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS-III at both 6- and 12-month follow-ups ( < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow-up times. For the sub-scores of UPDRS-III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor ( = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS-III total score at a median follow-up of 12 months ( = 0.030).
CONCLUSION
The current study confirmed the value of preoperative levodopa responsiveness for prediction of the short-term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short-term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long-term motor outcomes were highlighted by this study.
PubMed: 35146054
DOI: 10.1002/mdc3.13379 -
International Journal of Environmental... Dec 2021Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia.... (Review)
Review
Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016-2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg ( = 0.0138) and 100 mg ( = 0.0006) have improved the Unified Parkinson's Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression-Change (CGI-C), Clinical Global Impression-Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson's Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Pharmaceutical Preparations; Psychotic Disorders; United States
PubMed: 35010624
DOI: 10.3390/ijerph19010364 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
American Journal of Speech-language... Jan 2022Dysphagia is a common sequela of Parkinson disease (PD) and is associated with malnutrition, aspiration pneumonia, and mortality. This review article synthesized...
PURPOSE
Dysphagia is a common sequela of Parkinson disease (PD) and is associated with malnutrition, aspiration pneumonia, and mortality. This review article synthesized evidence regarding the effectiveness of interventions for dysphagia in PD.
METHOD
Electronic searches were conducted in Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and speechBITE. Of the 2,015 articles identified, 26 met eligibility criteria: interventional or observational studies with at least five or more participants evaluating dysphagia interventions in adults with PD-related dysphagia, with outcomes measured using videofluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), or electromyography (EMG). Risk of bias (RoB) was evaluated using the Evidence Project tool and predetermined criteria regarding the rigor of swallowing outcome measures.
RESULTS
Interventions were classified as follows: pharmacological ( = 11), neurostimulation ( = 8), and behavioral ( = 7). Primary outcome measures varied across studies, including swallowing timing, safety, and efficiency, and were measured using VFSS ( = 17), FEES ( = 6), and EMG ( = 4). Critical appraisal of study findings for RoB, methodological rigor, and transparency showed the majority of studies failed to adequately describe contrast media used, signal acquisition settings, and rater blinding to time point. Low certainty evidence generally suggested improved swallow timing with exercises with biofeedback and deep brain stimulation (DBS), improved safety with DBS and expiratory muscle strength training, and improved efficiency with the Lee Silverman Voice Treatment and levodopa.
CONCLUSIONS
Studies with lower RoB and greater experimental rigor showed potential benefit in improving swallowing efficiency but not safety. Further research investigating discrete changes in swallowing pathophysiology post-intervention is warranted to guide dysphagia management in PD.
SUPPLEMENTAL MATERIAL
https://doi.org/10.23641/asha.17132162.
Topics: Adult; Biofeedback, Psychology; Deep Brain Stimulation; Deglutition; Deglutition Disorders; Exercise Therapy; Humans; Parkinson Disease; Physical Therapy Modalities
PubMed: 34890260
DOI: 10.1044/2021_AJSLP-21-00145 -
Medicine Nov 2021Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.
BACKGROUND
Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.
RESULTS
Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).
CONCLUSIONS
P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.
Topics: Antiparkinson Agents; Combined Modality Therapy; Humans; Levodopa; Multicenter Studies as Topic; Parkinson Disease; Pramipexole; Treatment Outcome
PubMed: 34871213
DOI: 10.1097/MD.0000000000027511