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2.
JAMA ; 323(6): 548-560, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32044947

RESUMO

Importance: Parkinson disease is the most common form of parkinsonism, a group of neurological disorders with Parkinson disease-like movement problems such as rigidity, slowness, and tremor. More than 6 million individuals worldwide have Parkinson disease. Observations: Diagnosis of Parkinson disease is based on history and examination. History can include prodromal features (eg, rapid eye movement sleep behavior disorder, hyposmia, constipation), characteristic movement difficulty (eg, tremor, stiffness, slowness), and psychological or cognitive problems (eg, cognitive decline, depression, anxiety). Examination typically demonstrates bradykinesia with tremor, rigidity, or both. Dopamine transporter single-photon emission computed tomography can improve the accuracy of diagnosis when the presence of parkinsonism is uncertain. Parkinson disease has multiple disease variants with different prognoses. Individuals with a diffuse malignant subtype (9%-16% of individuals with Parkinson disease) have prominent early motor and nonmotor symptoms, poor response to medication, and faster disease progression. Individuals with mild motor-predominant Parkinson disease (49%-53% of individuals with Parkinson disease) have mild symptoms, a good response to dopaminergic medications (eg, carbidopa-levodopa, dopamine agonists), and slower disease progression. Other individuals have an intermediate subtype. For all patients with Parkinson disease, treatment is symptomatic, focused on improvement in motor (eg, tremor, rigidity, bradykinesia) and nonmotor (eg, constipation, cognition, mood, sleep) signs and symptoms. No disease-modifying pharmacologic treatments are available. Dopamine-based therapies typically help initial motor symptoms. Nonmotor symptoms require nondopaminergic approaches (eg, selective serotonin reuptake inhibitors for psychiatric symptoms, cholinesterase inhibitors for cognition). Rehabilitative therapy and exercise complement pharmacologic treatments. Individuals experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off ("off periods"), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation. Palliative care is part of Parkinson disease management. Conclusions and Relevance: Parkinson disease is a heterogeneous disease with rapidly and slowly progressive forms. Treatment involves pharmacologic approaches (typically with levodopa preparations prescribed with or without other medications) and nonpharmacologic approaches (such as exercise and physical, occupational, and speech therapies). Approaches such as deep brain stimulation and treatment with levodopa-carbidopa enteral suspension can help individuals with medication-resistant tremor, worsening symptoms when the medication wears off, and dyskinesias.


Assuntos
Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Carbidopa/uso terapêutico , Terapia Combinada , Estimulação Encefálica Profunda , Diagnóstico Diferencial , Progressão da Doença , Combinação de Medicamentos , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/fisiopatologia , Prognóstico
3.
Expert Opin Pharmacother ; 20(18): 2201-2207, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31670988

RESUMO

Introduction: Parkinson's disease is a neurodegenerative disorder which is characterized by the combination of motor and non-motor symptoms. As yet, there is no curative treatment. The gold standard for symptom control is levodopa. Two years after the start of substitution therapy, around 50% of patients experience some degree of fluctuation in motor performance. Catechol-O-methyltransferase (COMT) inhibitors are important agents in treating these fluctuations.Areas covered: This article summarizes our knowledge about a new third-generation COMT inhibitor, namely opicapone (OPC) (Search period: 2016-2019). The authors detail the pharmacological profile of OPC and summarize the results of completed clinical trials. In addition, they briefly summarize the achievements of the past few years.Expert opinion: Based on clinical trials conducted so far, OPC is an effective and safe new drug. In comparison to entacapone and tolcapone, it does not require close laboratory monitoring or multiple oral administrations, which may result in better adherence. No serious adverse event was reported during the drug development phases. Dyskinesia was the most common complaint. Further comparative studies and broader trial inclusion criteria are needed to help the decision between COMT inhibitors and to expand the patient spectrum where this drug can be applied.


Assuntos
Antiparkinsonianos/uso terapêutico , Oxidiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Administração Oral , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Catecóis/uso terapêutico , Discinesia Induzida por Medicamentos/etiologia , Humanos , Levodopa/uso terapêutico , Nitrilos/uso terapêutico
4.
Mymensingh Med J ; 28(4): 762-766, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31599238

RESUMO

Stroke is one of the leading cause of disability worldwide. Motor function deficits due to stroke contribute to overall low quality of life. The objective was of this study is to observe functional motor outcome after stroke with low dose Levodopa therapy. This prospective follow up study was carried out in the Department of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2014 to June 2016 to see the effect of low dose of Levodopa (110mg) on motor outcome after stoke disability. Motor deficit was measured by Medical Research Council (MRC) grading and Rivermead Mobility Index (RMI) score. Two groups were selected by simple random method, consisted of both ischemic and hemorrhagic stroke. All the patients of both the groups were suffering from at least some post stroke motor disability and attended full course of physiotherapy. The group (L) received 110mg Levodopa with physiotherapy. On the other hand (NL) group received only physiotherapy. They were all followed up for four times within two months of time and were assessed for recovery of motor function. Mean age was 59.03±11.56 years in Levodopa (L) group and 57.10±12.41 years in the Non Levodopa (NL) group; Males were predominant in both groups. Ninety three (77.50%) cases had ischemic stroke and 27(22.50%) cases had hemorrhagic stroke. Most common risk factors were hypertension and smoking. No known risk factor was detected in 8 (6.67%) patients. Single or multiple risk factors were confirmed in 112 patients (93.33%). MRC score was significantly higher both in affected upper and lower limb in Levodopa group comparing non Levodopa group at 4th visit. RMI score was also significantly higher in Levodopa group comparing non Levodopa group at 4th visit. The Levodopa (L) group showed better recovery pattern than Non Levodopa (NL) group. It can be concluded that motor recovery was better with administration of a single low dose of Levodopa in combination with physiotherapy. Motor outcome was significantly higher in levodopa group than non-levodopa group.


Assuntos
Pessoas com Deficiência , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Transtornos Motores/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Bangladesh , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
5.
Neurology ; 93(16): e1526-e1534, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31527282

RESUMO

OBJECTIVE: To determine the frequency, evolution, and associated features of orthostatic hypotension (OH) over 7 years of prospective follow-up in a population-based, initially drug-naive Parkinson disease (PD) cohort. METHODS: We performed repeated lying and standing blood pressure measurements in 185 patients with newly diagnosed PD and 172 matched normal controls to determine the occurrence of (1) OH using consensus-based criteria and (2) clinically significant OH (mean arterial pressure in standing position ≤75 mm Hg). We applied generalized estimating equations models for correlated data to investigate associated features of these 2 outcomes in patients with PD. RESULTS: OH was more common in patients with PD than controls at all visits, with the relative risk increasing from 3.0 (95% confidence interval [CI] 1.6-5.8; p < 0.001) at baseline to 4.9 (95% CI 2.4-10.1; p < 0.001) after 7 years. Despite a high cumulative prevalence of OH (65.4%) and clinically significant OH (29.2%), use of antihypotensive drugs was very rare (0.5%). OH was independently associated with older age (odds ratio [OR] 1.06 per year; 95% CI 1.03-1.10), lower Mini-Mental State Examination score (OR 0.91 [0.85-0.97] per unit), and longer follow-up time (OR 1.12 [1.03-1.23] per year). Clinically significant OH was associated with the same characteristics, in addition to higher levodopa equivalent dosage (OR 1.16 [1.07-1.25] per 100 mg). CONCLUSIONS: In this population-based study, we found OH to be a very frequent but undertreated complication in early PD, with associations to both disease-specific symptoms and drug treatment. Our findings suggest that clinicians should more actively assess and manage OH abnormalities in PD.


Assuntos
Pressão Sanguínea/fisiologia , Hipotensão Ortostática/fisiopatologia , Doença de Parkinson/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/tratamento farmacológico , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Estudos Prospectivos , Índice de Gravidade de Doença
6.
J Clin Neurosci ; 69: 281-284, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477464

RESUMO

We have evaluated an 82 years old PD patient who has acutely developed VH secondary to acute visual loss that was associated with increased electroencephalographic activity in the gamma range over the parietal, occipital and frontal regions. In this respect, we have tested the therapeutic effect of occipital lobe oriented rTMS application and its electrophysiological correlates that led to significant improvement in the hallucinatory symptomatology of the patient after two weeks. We have revealed that the improved hallucinatory symptoms after rTMS application resolved completely after switching from the pramipexole treatment to L-Dopa indicating that there could be a combined therapeutic effect of L-Dopa and rTMS. Furthermore, Quantitative-Electroencephalography analysis has shown that the therapeutic effects of rTMS and L-Dopa were seen with the improvement of impaired gamma power spectrum. Although the main limitation of this report is that this a single case study and that these findings need to be replicated in a larger sample, e.g., as part of a controlled trial, our present findings help us to enlighten the unknown pathophysiological overlapping between the visual hallucinations in PD and Charles Bonnet Syndrome. Finally, our study revealed increased gamma coherence and power spectrum which is seen with visual hallucinations and improved after the application of 1 Hz rTMS on the occipital lobe. These findings together suggest that rTMS could be used as a therapeutic tool for parkinsonian complex VH and probably due affecting gamma coherence and power spectrum.


Assuntos
Alucinações/etiologia , Alucinações/terapia , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Estimulação Magnética Transcraniana/métodos , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Eletroencefalografia , Humanos , Levodopa/uso terapêutico , Masculino , Pramipexol/uso terapêutico
7.
Gait Posture ; 74: 14-19, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31437733

RESUMO

BACKGROUND: Forward and backward walking are both impaired in Parkinson disease (PD). In this study, an exploratory factor analysis was performed to investigate the relationship between forward and backward walking in PD. RESEARCH QUESTION: Given the difference in levodopa response between forward and backward walking, what is the additive value of testing backwards walking in a clinical setting. METHODS: Sixty-two patients with PD (65.29 ± 7.17 yrs, UPDRS OFF = 29.68 ± 9.88, UPDRS ON = 16.40 ± 8.21) and eleven healthy age-matched controls (63.09 ± 8.09 yrs) were recruited. PD participants completed forward (F) and backward (B) walking tasks on a 6.1 m instrumented walkway (OFF and ON levodopa). Factor analysis was used to derive models for both walking tasks/medication states. RESULTS: In both OFF and ON, four factors were identified: Variability (OFF: F = 30.0%, B = 17.8%, ON: F = 21.6%, B = 25.0%), Rhythm (OFF: F = 14.5%, B = 17.0%, ON: F = 17.4%, B = 19.0%), Asymmetry (OFF: F = 13.7%, B = 14.3%, ON: F = 16.1%, B = 15.2%), and Pace (OFF: F = 12.2%, B = 17.0%, ON: F = 13.9%, B = 8.7%). In the ON state, a fifth factor was identified: Posture (ON: F = 3.8%, B = 7.7%). SIGNIFICANCE: This study demonstrates the similarity in gait domain factors in both forward and backward walking. While domains of gait are similar in both walking tasks, levodopa response is reduced in backward walking. This could be a result of the increased complexity of backward walking. This study provides a normative dataset that can be used when assessing forward and backward walking in individuals with PD.


Assuntos
Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Parkinson/fisiopatologia , Caminhada/fisiologia , Idoso , Estudos de Casos e Controles , Análise Fatorial , Feminino , Marcha/fisiologia , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Postura
8.
Rev Med Suisse ; 15(656): 1288-1290, 2019 Jun 19.
Artigo em Francês | MEDLINE | ID: mdl-31268258

RESUMO

Parkinson disease is a progressive neurodegenerative disease affecting the basal ganglia and causing the degeneration of dopaminergic neurons. It is a chronic affection with a slow evolution characterized by motor dysfunctions. Considering voice and speech, 90 % of patients present problems affecting their communication, social skills and quality of life. Although L-dopa has some effect on motor performance, speech and voice do not improve. So, the applicability and efficacy of non-pharmacological treatment, based on therapy is to be considered for voice impairment. Today, voice therapy is being viewed as a therapeutic option to be prescribed early in the course of Parkinson disease that may potentially contribute to slowing of motor symptom progression.


Assuntos
Doença de Parkinson , Distúrbios da Voz , Antiparkinsonianos/uso terapêutico , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/complicações , Qualidade de Vida , Distúrbios da Voz/tratamento farmacológico , Distúrbios da Voz/etiologia
9.
Brain Nerve ; 71(8): 857-867, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31346142

RESUMO

Over the last few decades, several delayed-start trials have suggested that early introduction of dopamine replacement therapy can improve the prognosis of Parkinson's disease (PD). Moreover, several observations support that L-dopa is non toxic to normal and diseased substantia nigra in humans. Thus, the clinical practice guideline 2018 for PD recommends L-dopa as an initial treatment for PD, in principle. More recently, several potential disease-modifying therapies have been reported to be effective. Furthermore, several recent studies suggest that exercise can be beneficial in delaying disease progression.


Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Guias de Prática Clínica como Assunto , Progressão da Doença , Dopamina/uso terapêutico , Exercício , Humanos , Doença de Parkinson/terapia , Substância Negra/fisiopatologia
10.
Nature ; 571(7766): 565-569, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316206

RESUMO

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5-8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1-/- mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease10.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/fisiopatologia , Intestinos/microbiologia , Doença de Parkinson/genética , Doença de Parkinson/microbiologia , Proteínas Quinases/deficiência , Proteínas Quinases/genética , Animais , Apresentação do Antígeno/imunologia , Autoantígenos/imunologia , Axônios/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Citrobacter rodentium/imunologia , Citrobacter rodentium/patogenicidade , Modelos Animais de Doenças , Neurônios Dopaminérgicos/imunologia , Neurônios Dopaminérgicos/patologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/patologia , Feminino , Intestinos/imunologia , Intestinos/patologia , Levodopa/uso terapêutico , Masculino , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/patologia , Neostriado/imunologia , Neostriado/microbiologia , Neostriado/patologia , Neostriado/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Proteínas Quinases/imunologia , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia
11.
Drugs Aging ; 36(9): 807-821, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31161581

RESUMO

Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico
12.
Biomolecules ; 9(6)2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216771

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons at level of substantia nigra pars compacta. To date, there is no cure for this pathology, except for some drugs able to alleviate the symptoms of PD. In this paper we report the synthesis and biological evaluation of novel sulfur- and selenyl-l-Dopa (LD) derivatives (SP1-6) obtained through the amide junction between the amino group of LD and carboxylic moiety of sulfur- and selenyl-organic compounds, which are commercially available. Biological activity was evaluated on human undifferentiated and retinoic acid/phorbol myristyl acetate (RA/PMA)-differentiated SY-SH5Y neuroblastoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activity against oxidative stress was measured using nitroblue tetrazolium (NBT) and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assays. Finally, physico-chemical characterization and plasma stability studies of SP1-6 were also performed. Biological data revealed that SP6 has a significant protective action against the neurotoxic action of 6-hydroxydopamine (6-OHDA) and H2O2 in a RA/PMA-differentiated SY-SH5Y neuroblastoma cell line that proved to be an effective antioxidant and protective compound. SP6, endowed with a lipophilic nature, low molecular weight, and plasma stability, can easily cross biological membranes via passive diffusion such as through the blood-brain barrier. SP6 has great potential for developing novel pharmacological approach for neurodegenerative diseases, such as PD. Further studies will help define its exact antioxidant mechanism and determine whether the neuroprotective action is mediated or modulated by glutathione peroxidase (GPx).


Assuntos
Levodopa/síntese química , Levodopa/farmacologia , Doença de Parkinson/tratamento farmacológico , Enxofre/química , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Humanos , Interações Hidrofóbicas e Hidrofílicas , Levodopa/química , Levodopa/uso terapêutico , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
13.
Ideggyogy Sz ; 72(5-6): 187-193, 2019 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31241263

RESUMO

Background and purpose: There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson's disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson's disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods: In our study we investigated the data of all Parkinson's patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists' usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: During the studied period a total of 2379 patients with Parkinson's disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson's disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion: The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.


Assuntos
Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Estudos Transversais , Humanos , Resultado do Tratamento
14.
Biomed Res Int ; 2019: 2382563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111044

RESUMO

Purpose: The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD). Methods: The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity. Results: Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of - 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. Conclusion: Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.


Assuntos
Administração Intranasal/métodos , Emulsões/uso terapêutico , Flavanonas/farmacologia , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Vitamina E/farmacologia , Animais , Antioxidantes , Comportamento Animal , Feminino , Levodopa/uso terapêutico , Masculino , Nanopartículas/química , Oxidopamina/efeitos adversos , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Viscosidade
15.
Expert Opin Pharmacother ; 20(10): 1181-1187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31058557

RESUMO

Introduction: Amantadine is an old, antiviral compound that moderately ameliorates impaired motor behaviour in Parkinson's disease. Its current resurgence results from the novel retarded release amantadine hydrochloride formulation, ADS5102, which has also received approval for the treatment of levodopa-related involuntary movements known as dyskinesia. Areas covered: This non-systematic, narrative drug evaluation discusses the value of ADS5102 for patients with Parkinson's disease. ADS5102 is orally applied once daily in the evening. This capsule provides higher and more continuous amantadine plasma concentrations than conventional amantadine immediate release formulations with their two to three times daily intake plan. Expert opinion: ADS5102 was superior to placebo in clinical trials. They aimed for the amelioration of motor complications, particularly at 'OFF' periods and with dyskinesia in fluctuating levodopa treated patients with Parkinson's disease. Side effects and tolerability were similar to the well-known effects of conventional amantadine formulations. ADS5102 simplifies treatment and improves compliance problems in the long run. The marketing of ADS5102 outside the US will be complex for return of research costs and investments required for its manufacturing. Indeed, worldwide institutional price regulation scenarios often only consider new therapeutic mode of actions as being innovative as opposed to old drugs with improved pharmacokinetic behaviour.


Assuntos
Amantadina/administração & dosagem , Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antivirais/uso terapêutico , Preparações de Ação Retardada , Discinesia Induzida por Medicamentos/etiologia , Humanos , Levodopa/uso terapêutico , Cooperação do Paciente
16.
Behav Neurol ; 2019: 7470904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065297

RESUMO

Objectives: We aimed to investigate the prevalence of restless leg syndrome (RLS) and exploring the contributing factors that affect the development of RLS in Parkinson's disease (PD) patients. Methods: A cross-sectional study was conducted consisting of 178 consecutive PD patients from our hospital between October 2015 and August 2016. We divided the participants into two groups, which were PD with RLS and PD with non-RLS. Then, we recorded their demographics and clinical data to draw a comparison between PD with RLS and PD with non-RLS. Results: 23 (12.92%) were diagnosed with RLS among all the enrolled PD patients. Unified Parkinson's Disease Rating Scale III (UPDRS III) and Hamilton Depression Scale (HAMD) scores, probable rapid eye movement sleep behavior disorder (PRBD), and daily levodopa equivalent dose (LED) in the PD with the RLS group were significantly different from those in the PD with the non-RLS group. Daily LED and the scores of UPDRS III and HAMD in PD patients with RLS were all higher than those in PD patients with non-RLS. PRBD, daily LED, and HAMD scores were significantly independent factors contributing to the development of RLS (OR = 4.678, 95% CI 1.372~15.944, P = 0.014; OR = 1.003, 95% CI 1.001~1.005, P = 0.019; OR = 1.094, 95% CI 1.002~1.193, P = 0.045). The severity of RLS was positively correlated with the duration of PD and daily LED (r = 0.438, P = 0.036; r = 0.637, P = 0.001). Conclusion: PRBD existence, daily LED, and HAMD scores are independent factors for developing RLS in PD patients. PRBD existence is firstly proposed as an independent factor in developing RLS among PD patients. RLS severity in PD patients are positively associated with the duration of PD and daily LED.


Assuntos
Doença de Parkinson/fisiopatologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Síndrome das Pernas Inquietas/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Prevalência , Escalas de Graduação Psiquiátrica , Transtorno do Comportamento do Sono REM/complicações , Síndrome das Pernas Inquietas/complicações , Inquéritos e Questionários
17.
Rev Assoc Med Bras (1992) ; 65(4): 541-546, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31066807

RESUMO

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Antiparkinsonianos/uso terapêutico , Brasil , Tomada de Decisão Clínica , Estimulação Encefálica Profunda/efeitos adversos , Humanos , Levodopa/uso terapêutico , Atividade Motora , Doença de Parkinson/fisiopatologia , Fatores de Risco , Resultado do Tratamento
18.
Neurosci Lett ; 705: 172-176, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31054924

RESUMO

Although cystatin C (Cys C) has been implicated in the pathophysiology of Parkinson's disease (PD), whether it can be used as a tool for evaluating dyskinesia is unknown. In the present study, the association of Cys C with dyskinesia in PD patients was investigated. Fasting serum Cys C levels were measured from 120 PD patients and 156 healthy controls. Demographic information was collected for all patients. In addition, levodopa (L-dopa)-equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) score, Hoehn and Yahr (H&Y) stage, and dyskinesia were assessed in PD patients. Receiver operating characteristic (ROC) curves were adopted to assess the evaluating accuracy of Cys C levels for distinguishing dyskinesia in PD patients. Patients with PD exhibited significantly higher serum Cys C levels compared with heathy controls. Dyskinesia was observed in 32 patients (26.7%). Multiple logistic regression showed serum Cys C levels (odds ratio, OR 12.93; 95% confidence interval, CI 1.08-54.23; p = 0.043), duration of disease (OR 1.03, 95% CI 1.01-1.05, p = 0.001) and UPDRS II score (OR 1.07, 95% CI 1.01-1.14, p = 0.019) were independently associated with dyskinesia. The ROC curve for the Cys C levels yielded a valuable accuracy for distinguishing dyskinesia in PD patients. Serum Cys C levels were independently associated with dyskinesia and may be a valuable screening tool for differentiating dyskinesia in PD patients. Although the pathophysiological mechanism of PD is complicated, the results from our study provide a better understanding of the association between Cys C and dyskinesia in PD patients and may yield insights into the pathogenesis of PD.


Assuntos
Cistatina C/sangue , Discinesias/diagnóstico , Doença de Parkinson/sangue , Valor Preditivo dos Testes , Idoso , Estudos de Casos e Controles , Discinesias/sangue , Discinesias/complicações , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Índice de Gravidade de Doença
19.
Neurology ; 92(22): e2559-e2570, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31043471

RESUMO

OBJECTIVE: To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms "off" and "on" levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality. RESULTS: Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery ("on" dopamine/"on" STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score). CONCLUSIONS: We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/mortalidade , Doença de Parkinson/terapia , Antiparkinsonianos/uso terapêutico , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Levodopa/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Prognóstico , Núcleo Subtalâmico
20.
Acta Neurol Scand ; 140(2): 157-161, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31025312

RESUMO

BACKGROUND: Few studies have suggested that levodopa-carbidopa intestinal gel (LCIG) may have a benefit on Parkinson's disease (PD) axial signs. AIMS OF THE STUDY: To investigate the long-term effect of LCIG on axial signs and the related prognostic factors. METHODS: A retrospective study on 49 PD patients treated with LCIG. Axial signs as per the Unified Parkinson Disease Rating Scale axial score (AS), Hoehn and Yahr (H&Y) scale, and levodopa equivalent daily dose (LEDD) were assessed at baseline (before starting LCIG treatment) and at the last follow-up (FU). RESULTS: After 47.6 ± 30 months of treatment, total AS deteriorated while motor complications still improved, in spite of a significant LEDD/Kg increment. When adjusted for LCIG treatment duration, a higher AS and freezing of gait severity at FU were predicted by a baseline lower response to l-dopa and higher H&Y (P < 0.01) and they were related to a lower independency in activity of daily life at FU (P < 0.001). Single axial items remain stable up to one year and postural instability up to four years. CONCLUSION: Baseline disease severity and the magnitude of l-dopa response predict axial signs' severity after around four years of LCIG treatment, with consequent implication on patients' functional independence.


Assuntos
Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Administração através da Mucosa , Idoso , Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Combinação de Medicamentos , Feminino , Marcha , Géis/farmacologia , Géis/uso terapêutico , Humanos , Mucosa Intestinal/efeitos dos fármacos , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural
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