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1.
Bol. latinoam. Caribe plantas med. aromát ; 22(6): 837-847, nov. 2023. tab, graf
Article in English | LILACS | ID: biblio-1554245

ABSTRACT

Cinnamon ( Cinnamomum verum J. Presl) is a well - known medicinal plant considered as an effective treatment for neurological disorders based on Persian medicine . The aim of the present study was assessing the effect of cinnamon oil, cinnamic acid, and cinnamaldehyde, on the in vitro model of Parkinson's disease (PD). Cinnamon oil, prepared in sesame oil, was phytochemically analyzed using high performance liquid chromatography (HPLC). Pheochromocytoma - 12 (PC - 12) cells were treated with 1 - methyl - 4 - phenyl - 1,2,3,6 - tetrahydropyridine (MPTP) as an in vitro model of neurodegeneration in PD. Cell viability, activity of caspase enzymes, and formation of reactive oxygen sp ecies (ROS) were evaluated. MPTP significantly decreased cell viability and increased Casp activity, as well as ROS formation. Cinnamon oil and cinnamic acid at 200 µg/m L could significantly reverse MPTP - induced abnormalities in PC - 12 cells including Casp activity and ROS formation. Our study supports the beneficial effect of cinnamon oil in neurodegeneration. Furt her investigations are needed to clarify the mechanisms and main active components.


La canela ( Cinnamomum verum J. Presl) es una planta medicinal m uy conocida, y considerada como un tratamiento efectivo para patologías neurológicas según la medicina persa. El objetivo de este estudio fue evaluar el efecto del aceite de canela, el ácido cinámico, y el cinamaldehído, en un modelo in vitro de la enferme dad de Parkinson (PD). El aceite de canela, preparado en aceite de sésamo, fue analizado fitoquímicamente usando cromatografía líquida de alta eficacia (HPLC). Se trataron células con feocromocitoma - 12 (P - 12) usando 1 - metil - 4 - fenil - 1,2,3,6 - tetrahidropiridi na (MPTP) como un modelo in vitro de neurodegeneración en PD. Se evaluó la viabilidad celular, actividad de enzimas caspasa, y formación de especies reactivas del oxígeno (ROS). El tratamiento con MPTP disminuyó significativamente la viabilidad celular y a umentó la actividad casp, así la formación de ROS. Aceite de canela y ácido cinámico a 200 µg/mL podría revertir significativamente las anormalidades inducidas por MPTP en células PC - 12, incluyendo la actividad casp y la formación de ROS. Nuestro estudio e ntrega sustento sobre los efectos benéficos del aceite de canela en la neurodegeneración. Se requiere más investigación para clarificar los mecanismos y los principales componentes activos.


Subject(s)
Animals , Rats , Parkinson Disease/drug therapy , Oils, Volatile/administration & dosage , Cinnamomum zeylanicum/chemistry , Acrolein/analogs & derivatives , Oils, Volatile/chemistry , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Chromatography, High Pressure Liquid , Cinnamates , PC12 Cells , Reactive Oxygen Species , Neurodegenerative Diseases/drug therapy , Disease Models, Animal , Medicine, Traditional
2.
Biol. Res ; 56: 27-27, 2023. tab, graf, ilus
Article in English | LILACS | ID: biblio-1513739

ABSTRACT

BACKGROUND: The underlying mechanism of Parkinson's disease are still unidentified, but excitotoxicity, oxidative stress, and neuroinflammation are considered key actors. Proliferator activated receptors (PPARs) are transcription factors involved in the control of numerous pathways. Specifically, PPARß/δ is recognized as an oxidative stress sensor, and we have previously reported that it plays a detrimental role in neurodegeneration. METHODS: Basing on this concept, in this work, we tested the potential effects of a specific PPARß/δ antagonist (GSK0660) in an in vitro model of Parkinson's disease. Specifically, live-cell imaging, gene expression, Western blot, proteasome analyses, mitochondrial and bioenergetic studies were performed. Since we obtained promising results, we tested this antagonist in a 6-hydroxydopamine hemilesioned mouse model. In the animal model, behavioral tests, histological analysis, immunofluorescence and western blot of substantia nigra and striatum upon GSK0660 were assayed. RESULTS: Our findings suggested that PPARß/δ antagonist has neuroprotective potential due to neurotrophic support, anti-apoptotic and anti-oxidative effects paralleled to an amelioration of mitochondria and proteasome activity. These findings are strongly supported also by the siRNA results demonstrating that by silencing PPARß/δ a significative rescue of the dopaminergic neurons was obtained, thus indicating an involvement of PPARß/δ in PD's pathogenesis. Interestingly, in the animal model, GSK0660 treatment confirmed neuroprotective effects observed in the in vitro studies. Neuroprotective effects were highlighted by the behavioural performance and apomorphine rotation tests amelioration and the reduction of dopaminergic neuronal loss. These data were also confirmed by imaging and western blotting, indeed, the tested compound decreased astrogliosis and activated microglia, concomitant with an upregulation of neuroprotective pathways. CONCLUSIONS: In summary, PPARß/δ antagonist displayed neuroprotective activities against 6-hydroxydopamine detrimental effects both in vitro and in vivo models of Parkinson's disease, suggesting that it may represent a novel therapeutic approach for this disorder.


Subject(s)
Animals , Mice , Parkinson Disease/drug therapy , Neuroprotective Agents/pharmacology , PPAR-beta , Oxidopamine , Proteasome Endopeptidase Complex
3.
Article in Portuguese | LILACS, CONASS, ColecionaSUS, SES-GO | ID: biblio-1553984

ABSTRACT

Rotigotina e outros medicamentos antiparkinsonianos, com ênfase em agonistas dopaminérgicos (bromocriptina e pramipexol). Indicação: Tratamento da doença de Parkinson. Pergunta: Há superioridade de eficácia e segurança da rotigotina, comparado aos agonistas dopaminérgicos disponíveis atualmente no SUS para o tratamento da doença de Parkinson? Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PubMed e utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Foram selecionadas três revisões sistemáticas que atendiam aos critérios de inclusão. A rotigotina não apresenta eficácia e segurança superiores ao pramipexol; não há quantidade de estudos suficientes para comparação com a bromocriptina


Rotigotine and other antiparkinsonians medicines, with emphasis on dopaminergic agonists (bromocriptine and pramipexole). Indication: Treatment of Parkinson disease. Question: Is rotigotine more effective and safer than other dopamine agonists available in the Brazilian Public Health System for the treatment of Parkinson's Disease? Rapid evidence review (overview) from systematic reviews, with a literature search in the PubMed database by employing a structured strategy. The methodological quality of systematic reviews was evaluated using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Three systematic reviews that met the inclusion criteria were selected. Rotigotine has not shown superior efficacy and safety when compared to pramipexole; there are insufficient studies for comparison with bromocriptine


Subject(s)
Parkinson Disease/drug therapy , Bromocriptine/therapeutic use , Dopamine Agonists , Pramipexole/therapeutic use , Antiparkinson Agents/therapeutic use
4.
Bol. latinoam. Caribe plantas med. aromát ; 21(2): 131-155, mar. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1393364

ABSTRACT

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.


Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.


Subject(s)
Humans , Plant Extracts/administration & dosage , Central Nervous System Diseases/drug therapy , Bacopa/chemistry , Parkinson Disease/drug therapy , Saponins/analysis , Schizophrenia/drug therapy , Triterpenes/analysis , Plant Extracts/chemistry , Central Nervous System/drug effects , Cognition/drug effects , Epilepsy/drug therapy , Alzheimer Disease/drug therapy , Phytochemicals
5.
Rev. chil. neuro-psiquiatr ; Rev. chil. neuro-psiquiatr;60(1): 62-74, mar. 2022. tab
Article in Spanish | LILACS | ID: biblio-1388421

ABSTRACT

Resumen La enfermedad de Parkinson (EP) es una enfermedad multisistémica de naturaleza neurodegenerativa, que clínicamente se caracteriza por presencia de síntomas motores como bradicinesia, rigidez, temblor en reposo e inestabilidad postural. Sin embargo, también pueden estar presentes síntomas no motores que constituyen trastornos del ánimo, trastornos del sueño, disfunción cognitiva o disfunción autonómica. Dentro de las disfunciones autonómicas, los síntomas urinarios se han documentado en los pacientes con enfermedad de Parkinson. Los síntomas urinarios más comunes son la nicturia, urgencia urinaria, aumento de la frecuencia miccional e incontinencia de urgencia. El presente artículo hace una revisión narrativa de la literatura actual sobre los mecanismos fisiopatológicos, manifestaciones clínicas, diagnóstico y tratamiento de la disfunción urinaria en pacientes con enfermedad de Parkinson.


Parkinson's disease (PD) is a neurodegenerative multisystemic diseases, which is clinically characterized by the presence of motor symptoms such as bradykinesia, rigidity, resting tremor, and postural instability. However, non-motor symptoms constituting mood disorders, sleep disorders, cognitive dysfunction, or autonomic dysfunction may also be present. Within autonomic dysfunctions, urinary symptoms have been documented in patients with Parkinson's disease. The most common urinary symptoms are nocturia, urinary urgency, increased urinary frequency, and urge incontinence. This article makes a narrative review of the current literature on the pathophysiological mechanisms, clinical manifestations, diagnosis and treatment of urinary dysfunction in patients with Parkinson's disease.


Subject(s)
Humans , Parkinson Disease/physiopathology , Urination Disorders/physiopathology , Parkinson Disease/drug therapy , Urination Disorders/diagnosis , Urination Disorders/drug therapy , Urinary Bladder, Neurogenic
6.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;80(1): 56-61, Jan. 2022. tab, graf
Article in English | LILACS | ID: biblio-1360133

ABSTRACT

ABSTRACT Background: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. Objective: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. Methods: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. Results: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Conclusions: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.


RESUMO Antecedentes: Comportamentos impulsivo-compulsivos (CICs) podem acometer uma parcela significativa de indivíduos com doença de Parkinson (DP). Objetivo: Nós estudamos amostras de tecido cerebral de uma população de pacientes com DP de um banco de cérebros que receberam apomorfina por infusão contínua em vida, com a finalidade de avaliar a prevalência e o desfecho dos CICs. Métodos: Uma pesquisa no banco de dados do Banco de Cérebros de Queen Square foi conduzida à procura de doações recebidas entre 2005 e 2016 com diagnóstico anatomopatológico de DP idiopática. Os prontuários de todos os doadores que usaram apomorfina por infusão contínua por um período mínimo de três meses foram revisados. Dados clínicos e demográficos foram coletados, assim como informações detalhadas sobre o tratamento, prevalência e desfecho dos CICs. Resultados: 193 casos de DP, 124 do sexo masculino e 69 do sexo feminino, com idade média de início da doença de 60,2 anos e tempo médio de duração da doença de 17,2 anos, foram revisados. Aproximadamente metade dos casos apresentaram demência, um quarto depressão, e um pouco mais de 40% discinesias. A prevalência de CICs foi 14,5%. Vinte e quatro indivíduos usaram infusão de apomorfina por mais de três meses. Os pacientes que usaram apomorfina apresentaram DP mais cedo, maior duração da doença, e uma maior prevalência de discinesias. A prevalência de novos casos de CICs entre pacientes usando apomorfina foi de 8,3%. Infusão de apomorfina foi usada em média por 63,1 meses a um dose máxima média de 79,5 mg por dia. Dez pacientes permaneceram usando apomorfina até o óbito. Conclusões: Apomorfina pode ser usada como opção de tratamento alternativo para pacientes que apresentarem CICs no passado considerando seu baixo risco de causar recorrência de CICs.


Subject(s)
Humans , Male , Female , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Dyskinesias , Disruptive, Impulse Control, and Conduct Disorders , Apomorphine , Prevalence , Retrospective Studies , Compulsive Behavior/drug therapy , Compulsive Behavior/epidemiology , Impulsive Behavior
7.
Zhongguo Zhong Yao Za Zhi ; (24): 499-510, 2022.
Article in Chinese | WPRIM | ID: wpr-927995

ABSTRACT

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1β, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.


Subject(s)
Animals , Rats , Gastrointestinal Microbiome , NF-kappa B/metabolism , Nardostachys/metabolism , Parkinson Disease/drug therapy , Rats, Sprague-Dawley
8.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;79(11): 989-994, Nov. 2021. tab
Article in English | LILACS | ID: biblio-1350142

ABSTRACT

ABSTRACT Background: Impulse control disorders (ICD) occur frequently in individuals with Parkinson's disease. So far, prevention is the best treatment. Several strategies for its treatment have been suggested, but their frequency of use and benefit have scarcely been explored. Objective: To investigate which strategy is the most commonly used in a real-life setting and its rate of response. Methods: A longitudinal study was conducted. At the baseline evaluation, data on current treatment and ICD status according to QUIP-RS were collected. The treatment strategies were categorized as "no-change", dopamine agonist (DA) dose lowering, DA removal, DA switch or add-on therapy. At the six-month follow-up visit, the same tools were applied. Results: A total of 132 individuals (58.3% men) were included; 18.2% had at least one ICD at baseline. The therapeutic strategy most used in the ICD group was no-change (37.5%), followed by DA removal (16.7%), DA switch (12.5%) and DA lowering (8.3%). Unexpectedly, in 20.8% of the ICD subjects the DA dose was increased. Overall, nearly 80% of the subjects showed remission of their ICD at follow-up. Conclusions: Regardless of the therapy used, most of the subjects presented remission of their ICD at follow-up Further research with a longer follow-up in a larger sample, with assessment of decision-making processes, is required in order to better understand the efficacy of strategies for ICD treatment.


Resumen Antecedentes: Los trastornos del control de impulsos (TCI) son frecuentes en personas con enfermedad de Parkinson. A la fecha, la prevención es el mejor tratamiento. Existen varias estrategias sugeridas para su tratamiento, pero su frecuencia de uso y beneficio ha sido escasamente explorada. Objetivo: Investigar qué estrategia es la más utilizada en un entorno de la vida real y su tasa de respuesta. Métodos: Se realizó un estudio longitudinal. En la evaluación inicial, se recopiló el tratamiento actual y el estado del TCI de acuerdo con el QUIP-RS. La estrategia de tratamiento se clasificó como "sin cambios", reducción de la dosis de agonista de la dopamina (AD), eliminación de AD, cambio de AD o terapia complementaria. En la visita de seguimiento a los 6 meses, se aplicaron las mismas herramientas. Resultados: Se incluyeron un total de 132 (58.3% hombres) personas. El 18.2% tenía al menos un TCI al inicio del estudio. La estrategia terapéutica más utilizada en el grupo de TCI fue sin cambios (37.5%), seguida de eliminación de DA (16.7%), cambio de AD (12.5%) y reducción de DA (8.3%). En el 20.8% de los sujetos con TCI se aumentó la dosis de AD. Casi el 80% de los sujetos tuvieron una remisión del TCI al seguimiento. Conclusiones: Independientemente de la terapia utilizada, la mayoría de los sujetos tuvieron una remisión del TCI. Se requiere más investigación con un seguimiento y una muestra mayor para evaluar l proceso de toma de decisiones para comprender mejor la eficacia de las estrategias.


Subject(s)
Humans , Male , Female , Parkinson Disease/complications , Parkinson Disease/drug therapy , Disruptive, Impulse Control, and Conduct Disorders/therapy , Longitudinal Studies , Dopamine Agonists/therapeutic use
9.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);67(1): 125-130, Jan. 2021. tab, graf
Article in English | LILACS | ID: biblio-1287781

ABSTRACT

SUMMARY OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson's disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a "red flag" that points to the need for a therapeutic drug review when its presence or worsening is detected.


Subject(s)
Humans , Male , Female , Parkinson Disease/drug therapy , Pain/etiology , Pain/drug therapy , Levodopa/adverse effects , Antiparkinson Agents/adverse effects
10.
Ciênc. Saúde Colet. (Impr.) ; 26(1): 197-208, jan. 2021. tab
Article in Portuguese | LILACS | ID: biblio-1153759

ABSTRACT

Resumo Este estudo avaliou a adesão de médicos ao Protocolo Clínico e Diretrizes Terapêuticas para a Doença de Parkinson (PCDT-DP), no âmbito do SUS. Dois métodos complementares foram utilizados: avaliação descritiva de 375 solicitações de medicamentos encaminhadas à Assistência Farmacêutica da Secretaria de Estado da Saúde do Rio Grande do Sul, de março a setembro de 2016, e levantamento por meio de questionário estruturado aos prescritores para investigar a percepção de barreiras à utilização. Apenas 5,33% das solicitações analisadas apresentaram adesão completa às recomendações do protocolo. As solicitações oriundas de especialistas em DP tiveram maior adesão aos critérios para o diagnóstico (p<0,05) e dose do medicamento (p<0,05). Dentre as respostas ao questionário destacaram-se como principais barreiras a falta de tempo para preenchimento dos documentos obrigatórios (52%) e nenhum ou pouco conhecimento sobre o protocolo (48%). Médicos com menor tempo de exercício de profissão tendem a perceber menos barreiras para a utilização do protocolo (p<0,05). Os resultados indicam a necessidade de ações de implementação do PCDT-DP à prática médica, direcionadas às equipes assistenciais e de gestão, e maior integração da assistência farmacêutica com a rede de atenção.


Abstract This study evaluated the adherence of physicians to the Clinical Protocol and Therapeutic Guidelines on Parkinson's Disease (CPTG-PD) within the scope of the Unified Health System (SUS). A descriptive analysis of 375 drug application documents sent to the Pharmaceutical Services of the Rio Grande do Sul State Public Health Department (AF/SES/RS) between March and September 2016, and a structured survey to evaluate the physician's perception about the protocol and barriers to its use was conducted. Only 5.33% of the requests analyzed presented all the necessary data, considering the criteria of the protocol. The requests from specialists had a higher percentage of adherence to the diagnostic and dose criteria (p<0.05). The main barriers to protocol use were the lack of awareness or familiarity with the protocol (48%) and the lack of time to complete the mandatory documents (52%). More recently qualified physicians tended to perceive fewer barriers to protocol use (p<0.05). The results indicate that actions are still necessary to implement the PCDT-DP in medical practice, focusing on care and management teams. Greater integration between pharmaceutical assistance and the healthcare network is needed.


Subject(s)
Humans , Parkinson Disease/drug therapy , Physicians , Perception , Practice Patterns, Physicians' , Brazil , Clinical Protocols , Guideline Adherence
11.
Journal of Integrative Medicine ; (12): 300-310, 2021.
Article in English | WPRIM | ID: wpr-888763

ABSTRACT

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.


Subject(s)
Animals , Antioxidants/pharmacology , Cell Line , Disease Models, Animal , Models, Animal , Neurodegenerative Diseases , Oxidative Stress , Parkinson Disease/drug therapy
13.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);42(2): 218-224, Mar.-Apr. 2020.
Article in English | LILACS | ID: biblio-1089257

ABSTRACT

Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.


Subject(s)
Humans , Animals , Parkinson Disease/drug therapy , Cannabidiol/therapeutic use , Neuroprotective Agents/therapeutic use , Disease Models, Animal , Clinical Studies as Topic
14.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;78(4): 206-216, Apr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1098084

ABSTRACT

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.


Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.


Subject(s)
Humans , Parkinson Disease/drug therapy , Levodopa/therapeutic use , Dyskinesia, Drug-Induced , Dopamine Agonists , Polymorphism, Single Nucleotide , Antiparkinson Agents
15.
Bol. latinoam. Caribe plantas med. aromát ; 19(5): 466-481, 2020. ilus, tab
Article in English | LILACS | ID: biblio-1283634

ABSTRACT

Neurodegeneration is a progressive loss of neurons both structurally and functionally causing neuronal cell death ultimately leading to development of various neurodegenerative diseases. Due to poor pharmacokinetic profile of neurotrophins, there still remains a challenge in their neurotrophic therapy where plants, bacteria and fungi, as natural products, could act as promising candidates against various neurological disorders by modulating the neurotrophic activity. Therefore, these natural products that mimic neurotrophins, could develop novel therapeutic approaches to herbal drug that can ameliorate neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and other associated neurological disorders. Taking into account the failure of strategies involving single neurotrophins for the treatment of neurodegenerative diseases, we propose a combination of small molecules of natural products that may work synergistically to restore neuronal functions, minimize side effects and target multiple pathways for a more effective treatment.


La neurodegeneración es una pérdida progresiva de neuronas, tanto estructural como funcional, que causa la muerte neuronal, lo que conduce al desarrollo de diversas enfermedades neurodegenerativas. Debido al pobre perfil farmacocinético de las neurotrofinas, existe un desafío en su terapia neurotrófica donde plantas, bacterias y hongos, como productos naturales, podrían actuar como candidatos contra diversos trastornos neurológicos al modular la actividad neurotrófica. Estos productos naturales que asemejan a las neurotrofinas podrían desarrollar enfoques terapéuticos novedosos como medicamentos a base de hierbas que pueden mejorar enfermedades neurodegenerativas como: Parkinson, Alzheimer y otros trastornos neurológicos asociados. Teniendo en cuenta el fracaso de las estrategias terapéuticas de neurotrofinas para las enfermedades neurodegenerativas, proponemos una combinación de pequeñas moléculas de productos naturales que pueden funcionar sinérgicamente para restaurar las funciones neuronales, minimizar los efectos secundarios y apuntar a múltiples vías para un tratamiento más efectivo.


Subject(s)
Humans , Biological Products/therapeutic use , Neuroprotective Agents/therapeutic use , Neurodegenerative Diseases/drug therapy , Parkinson Disease/drug therapy , Signal Transduction , Alzheimer Disease/drug therapy
16.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;77(7): 493-500, July 2019. graf
Article in English | LILACS | ID: biblio-1011363

ABSTRACT

ABSTRACT The present study was undertaken to investigate the effects of carvacrol and treadmill exercise on memory deficit, rotational behavior and oxidative stress biomarkers in a 6-OHDA-lesioned rat model of Parkinson's disease. Wistar rats were treated with carvacrol at a dose of 25 mg/kg and/or ran on a treadmill for a week. Then, 6-OHDA was microinjected into the medial forebrain bundle and treatments continued for six more weeks. Aversive memory, rotational behavior and oxidative stress biomarkers were assessed at the end of week six. The 6-OHDA-lesioned group showed a significant increase in rotational behavior and a decrease in step-through latency in the passive avoidance test compared with the sham group. These behaviors were accompanied by increased lipid peroxidation levels and decreased total thiol concentration in the striatum and/or hippocampus of the hemiparkinsonian rats. Moreover, treatment with carvacrol and exercise reduced rotational behavior and improved aversive memory deficit, which was accompanied by decreased lipid peroxidation levels and increased total thiol concentration in the striatum and/or hippocampus. In conclusion, treatment with carvacrol and treadmill exercise ameliorated motor and memory deficits by modulating oxidative stress in the striatum and hippocampus of hemiparkinsonian rats. Therefore, the combination of carvacrol and treadmill exercise could be an effective therapeutic tool for treatment of neurobehavioral deficits in Parkinson's disease patients.


RESUMO O presente estudo foi realizado para investigar os efeitos do carvacrol e do exercício em esteira sobre o déficit de memória, comportamento rotacional e biomarcadores de estresse oxidativo em um modelo animal (ratos lesionados por 6-OHDA) da doença de Parkinson (DP). Ratos Wistar foram tratados com carvacrol na dose de 25 mg/kg e/ou correram em uma esteira por uma semana. Depois, 6-OHDA foi microinjetada no feixe do prosencéfalo medial e os tratamentos continuaram por mais seis semanas. A memória aversiva, o comportamento rotacional e biomarcadores de estresse oxidativo foram avaliados no final da semana 6. O grupo 6-OHDA mostrou um aumento significativo no comportamento rotacional e uma diminuição na latência no teste de esquiva passiva em comparação com o grupo "sham". Estes comportamentos foram acompanhados por aumento dos níveis de peroxidação lipídica e diminuição da concentração total de tiol no estriado e/ou hipocampo de ratos hemiparkinsonianos. Além disso, o tratamento com carvacrol e exercício reduziu o comportamento rotacional e melhorou o déficit de memória aversiva, que foi acompanhado pela diminuição dos níveis de peroxidação lipídica e aumento da concentração total de tiol no estriado e/ou hipocampo. Em conclusão, o tratamento com carvacrol e exercícios em esteira melhorou os déficits motor e de memória, modulando o estresse oxidativo no estriado e no hipocampo de ratos hemiparkinsonianos. Portanto, a combinação de carvacrol e exercício em esteira pode ser uma ferramenta terapêutica eficaz para o tratamento de déficits neurocomportamentais em pacientes com DP.


Subject(s)
Animals , Male , Rats , Parkinson Disease/drug therapy , Cymenes/administration & dosage , Memory Disorders/drug therapy , Motor Activity , Parkinson Disease/complications , Physical Conditioning, Animal , Apomorphine/administration & dosage , Rats, Wistar , Oxidative Stress/drug effects , Disease Models, Animal , Memory Disorders/etiology
17.
Rev. bras. neurol ; 55(2): 17-32, abr.-jun. 2019. tab
Article in Portuguese | LILACS | ID: biblio-1010037

ABSTRACT

Os derivados canabinoides podem ser vistos como novos potenciais terapêuticos para o tratamento da doença de Parkinson e Alzheimer. Assim, esta revisão teve como objetivo descrever os efeitos terapêuticos e adversos do uso de canabidiol e de delta-9-tetrahidrocanabinol nas doenças de Parkinson e de Alzheimer. Para tanto, foi realizada uma busca na base de dados Medline no período entre 2007 e 2017. Os descritores utilizados foram (Tetrahydrocannabinol OR Cannabidiol) AND (Parkinson OR Alzheimer) AND (Treatment OR Therapeutics). Os resultados mostraram efeitos terapêuticos promissores do canabidiol e do delta-9-tetrahidrocanabinol nestas doenças, tais como redução de sintomas motores e cognitivos, e ação neuroprotetora. Estes resultados podem ser explicados, em parte, pelos efeitos antioxidante, antiinflamatório, antagonista de receptores CB1, ou pela ativação de receptores PPAR-gama produzido por estas substâncias. Além disso, poucos efeitos adversos foram descritos, como boca seca e sonolência. Nesse contexto, estes resultados evidenciam a necessidade de novas pesquisas a respeito dos efeitos terapêuticos e adversos de canabinoides com maiores doses e períodos de exposição, para quem sabe, em um futuro próximo, ser possível olhar estas substâncias como uma opção terapêutica mais eficaz e segura para estes pacientes.


Cannabinoid derivatives can be viewed as a novel therapeutic potentials for the treatment of Parkinson's and Alzheimer's disease. Thus, this review aimed to describe the therapeutic and adverse effects of the use of cannabidiol and delta-9-tetrahydrocannabinol in Parkinson's and Alzheimer's disease. A search of the Medline database was carried out between 2007 and 2017. The descriptors used were (Tetrahydrocannabinol OR Cannabidiol) AND (Parkinson OR Alzheimer) AND (Treatment OR Therapy). The results showed promising therapeutic effects of cannabidiol and delta-9-tetrahydrocannabinol in Parkinson and Alzheimer's diseases, such as the reduction of motor and cognitive symptoms and neuroprotective action. These results may be explained, in part, by the anti-inflammatory and antioxidant effects, by CB1 receptor antagonism, or by the activation of PPAR-gamma receptors, produced by these substances. In addition, few adverse effects have been reported, such as dry mouth and drowsiness. In this context, these results highlight the need for further research on the therapeutic and adverse effects of cannabinoids with higher doses and periods of exposure, for whom, in the near future, it is possible to view these substances as a more effective and safe therapeutic option for these patients.


Subject(s)
Humans , Animals , Aged , Rats , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Cannabinoids/therapeutic use , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Cannabinoids/administration & dosage , Cannabinoids/adverse effects , Double-Blind Method , Surveys and Questionnaires , Treatment Outcome , Animal Experimentation
18.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;77(1): 47-54, Jan. 2019. tab
Article in English | LILACS | ID: biblio-983873

ABSTRACT

ABSTRACT Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disorder (RLS/WED) are relatively common diseases in the realm of movement disorders. The fact that both may, as expected, co-occur and typically share a similar remarkable response to dopaminergic treatment raised the interest in exploration of additional shared features that throughout the years cruised fields as diverse as phenomenology, epidemiology, genetics, pathology, and clinical studies. In this review, we describe and critically examine the evidence and biases of a conceivable overlap of these two disorders, trying to shed light onto two main sources of confusion: (1) are PD and RLS/WED reciprocal risk factors? and (2) what are the main mimics of RLS/WED in PD?


RESUMO A doença de Parkinson (DP) e a síndrome das pernas inquietas/doença de Willis-Ekbom (SPI/DWE) são doenças relativamente comuns no campo dos distúrbios do movimento. O fato de que ambas podem, como esperado, ocorrer de forma simultânea e usualmente apresentarem resposta favorável ao tratamento dopaminérgico levaram ao interesse em explorar características compartilhadas adicionais. Ao longo dos últimos anos, essa busca percorreu campos diversos como a fenomenologia, epidemiologia, genética, patologia e estudos clínicos. Nesta revisão, analisamos e discutimos criticamente as evidências e os vieses de sobreposição concebíveis dessas duas doenças, tentando esclarecer duas perguntas sem resposta precisa até o momento: (1) DP e SPI/DWE representam fatores de risco recíprocos? e (2) quais são os principais mimetizadores da SPI/DWE na DP?


Subject(s)
Humans , Parkinson Disease/physiopathology , Parkinson Disease/drug therapy , Restless Legs Syndrome/physiopathology , Restless Legs Syndrome/drug therapy , Dopamine Agents/therapeutic use , Parkinson Disease/diagnosis , Parkinson Disease/genetics , Restless Legs Syndrome/diagnosis , Restless Legs Syndrome/genetics , Risk Factors , Treatment Outcome , Diagnosis, Differential
19.
CoDAS ; 31(1): e20170249, 2019. tab
Article in Portuguese | LILACS | ID: biblio-1039597

ABSTRACT

RESUMO Objetivo Analisar o efeito da levodopa na dinâmica coclear, bem como na via eferente olivococlear medial de indivíduos com doença de Parkinson idiopática (DP). Método Indivíduos com e sem DP, acompanhados em um hospital universitário, realizaram a pesquisa das emissões otoacústicas por produto de distorção (EOAPD) e do efeito inibitório das EOAPD (EIEOA) na presença de ruído contralateral. Foram estabelecidas as medidas de correlação entre os resultados das EOAPD e do EIEOA com estágio Hoehn&Yahr (H&Y), dose diária de levodopa e tempo de diagnóstico da DP. Além disso, as medidas eletroacústicas foram comparadas entre os indivíduos sem DP e com DP, estratificados de acordo com a dose de levodopa administrada diariamente. Resultados Foi identificada correlação fraca e negativa entre a amplitude das EOAPD com a dose diária de levodopa e correlações positivas, de força moderada e fraca, entre o EIEOA com a dose diária de levodopa e o tempo de diagnóstico da DP, respectivamente. A amplitude das EOAPD foi maior nos indivíduos com DP em uso de levodopa ≤ 600 miligramas quando comparada à de indivíduos sem DP e com DP, em uso de dose superior. Já o EIEOA foi menor nos indivíduos em uso de doses ≤ 600 miligramas, quando comparado aos demais grupos. Conclusão Doses diárias de levodopa iguais ou inferiores a 600 mg/dia aumentam as respostas mecanotransdutoras cocleares nas frequências de 2 e 3 kHz, enquanto que a ação dos sistemas eferentes olivococleares é reduzida nesta região.


ABSTRACT Purpose To evaluate the effect of levodopa on cochlear dynamics and on the medial olivocochlear efferent pathway of idiopathic Parkinson's disease (PD) individuals. Methods Individuals with and without PD, followed at a University Hospital, were submitted to Distortion Product Otoacoustic Emissions (DPOAE) and DPOAE Inhibitory Effect (OAEIE) in the presence of contralateral noise. Correlation measures between DPOAE and OAEIE results with Hoehn&Yahr (H&Y) stage, daily dose of levodopa and PD diagnosis period were established. Furthermore, electroacoustic measures were compared between individuals without and those with PD, stratified by dose of levodopa daily administered. Results Weak negative correlation between DPOAE amplitude and daily dose of levodopa was found, as well positive correlations between EIEOA with daily dose of levodopa and time of PD diagnosis, respectively. Higher DPOAE amplitude was found in individuals with PD using daily doses of levodopa ≤ 600 milligrams when compared to individuals without PD and those with PD using higher doses. EIEOA was lower in individuals using doses ≤ 600 milligrams, when compared to the other groups. Conclusion Daily doses of levodopa up to 600 mg / day increase the cochlear mechanical-transducer responses in 2 and 3 kHz frequencies, while the action of olivocochlear efferent systems is reduced in this region.


Subject(s)
Humans , Male , Female , Adult , Aged , Aged, 80 and over , Parkinson Disease/drug therapy , Levodopa/pharmacology , Otoacoustic Emissions, Spontaneous/drug effects , Antiparkinson Agents/pharmacology , Parkinson Disease/complications , Auditory Pathways/drug effects , Acoustic Stimulation , Middle Aged
20.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;76(12): 840-848, Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-983858

ABSTRACT

ABSTRACT Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.


RESUMO A optimização do tratamento da doença de Parkinson idiopática se faz um desafio, pois tem impacto direto na qualidade de vida do paciente. O melhor esquema terapêutico é o que permite o melhor controle motor com os menores efeitos adversos, através de terapêutica individualizada. A apomorfina é o único medicamento antiparkinsoniano que pode ser comparável à potência da levodopa no controle dos sintomas motores. Trata-se de um agonista dopaminérgico empregado na terapia de resgate em pacientes com flutuações motoras e também contribui para a melhora de muitos sintomas não motores. A via subcutânea, com injeções intermitentes, ou com infusão contínua, parece ser a melhor opção pela eficácia e tolerabilidade. Essa revisão resume aspectos históricos, estrutura da molécula, mecanismo de ação, indicação, contra-indicação e efeitos colaterais, compara a terapia de infusão com apomorfina com outros tratamentos, como a terapia oral, estimulação cerebral profunda e infusão enteral contínua de levodopa/carbidopa gel, e fornece instruções práticas de como iniciar o tratamento.


Subject(s)
Humans , Parkinson Disease/drug therapy , Apomorphine/administration & dosage , Dopamine Agonists/administration & dosage , Antiparkinson Agents/administration & dosage , Carbidopa , Levodopa , Deep Brain Stimulation , Drug Combinations
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