Tratamiento de la enfermedad de Parkinson temprana / Treatment of early Parkinson's disease

RESUMEN La enfermedad de Parkinson (EP) es principalmente una enfermedad de pacientes ancianos. Es un trastorno multifacético que comprende síntomas motores y no motores en todas las etapas de la enfermedad. Esta revisión busca integrar los datos de las opciones de tratamiento más recientes con los datos de las terapias establecidas, a fin de proporcionar una referencia actualizada basada en la evidencia para los médicos que tratan la EP temprana, con medicamentos que puedan usarse como alternativa a la levodopa. El enfoque de los médicos para el tratamiento de la enfermedad de Parkinson (EP) temprana debe tener en cuenta numerosos aspectos, entre ellos, cómo informar al paciente sobre el diagnóstico y la decisión crítica de qué terapia adoptar y cuándo iniciarla. El tratamiento del trastorno motor asociado con la EP temprana debe considerar varios factores cruciales, como la edad de inicio, las comorbilidades y los requisitos funcionales del paciente, y no se puede resumir en una fórmula simple. En pacientes más jóvenes (es decir, antes de la edad de 70 años) y en aquellos sin altos requisitos funcionales, el tratamiento generalmente se inicia con agonistas de dopamina y / o inhibidores de la enzima monoaminooxidasa-B (MAO- B I). En pacientes más jóvenes, la levodopa se debe agregar a los agonistas de la dopamina y / o MAO-B I, según lo requiera la progresión de la enfermedad, mientras que en los pacientes mayores, cuando la respuesta a la levodopa sola no es satisfactoria, los agonistas de la dopamina o los inhibidores de la catecol-O- metiltransferasa pueden posteriormente ser agregados.

SUMMARY Parkinson's disease (PD) is primarily a disease of elderly patients. Is a multifaceted disorder comprised of both motor and non-motor symptoms at all stages of the disease. This review seeks to integrate data from the newest treatment options with data from established therapies, so as to provide an up-to- date evidence-based reference for clinicians treating early PD, with medications that can be used as an alternative to levodopa. The clinicians' approach to the treatment of early Parkinson's disease (PD) should take into account numerous aspects, including how to inform a patient upon diagnosis and the critical decision of what therapy to adopt and when to start it. The treatment of the motor disorder associated with early PD needs to consider several crucial factors, such as age at onset, comorbidities, and the patient's functional requirements, and cannot be summarized in a simple formula. In younger patients (i.e., before the age of 70) and in those without high functional requirements, treatment is usually initiated with dopamine agonists and/or monoamine oxidase-B enzyme inhibitors (MAO-B I). In younger patients, levodopa should be added to dopamine agonists and/or MAO-B I, as required by disease progression, whereas in older patients, when response to levodopa alone is not satisfactory, dopamine agonists or catechol-O- methyltransferase inhibitors may subsequently be added.

Manejo perioperatorio de pacientes usuarios de antidepresivos / Perioperative management of patients using antidepressants

El uso de antidepresivos en el perioperatorio es muy frecuente, y la práctica clínica indica que los pacientes usuarios de antidepresivos que son sometidos a cirugía tienen un riesgo perioperatorio aumentado. No existen en la actualidad guías clínicas basadas en la evidencia que orienten el manejo de este tipo de pacientes, por lo que las recomendaciones se basan en las escasas revisiones sistemáticas y metaanálisis disponibles, reportes de casos y opinión de expertos, que en muchos casos resultan controversiales. La decisión de mantener o suspender la medicación antidepresiva implica considerar los riesgos tanto desde el punto de vista fisiológico (características generales del paciente, riesgos asociados al antidepresivo utilizado, la cirugía propiamente como tal, la interacción con fármacos frecuentemente utilizados en el perioperatorio, entre otros) como desde el punto de vista psiquiátrico (riesgo de síndrome de retirada, recaída de la enfermedad psiquiátrica, intentos suicidas), por lo que la decisión debe ser tomada idealmente de forma multidisciplinaria entre cirujanos, anestesiólogos y psiquiatras, con la idea de confeccionar un plan quirúrgico, anestésico y de manejo perioperatorio seguro para el paciente.

Antidepressant use in the perioperative is a common practice, and clinical evidence shows that surgical patients using antidepressants have an increased perioperative risk. There are not evidence-based guidelines for the perioperative management of these patients, and recommendations are based on few systematic reviews and meta-analysis, case reports and expert opinion, which in many cases are controversial. The decision to continue or discontinue the medication involves considering general patient characteristics, risks associated with the antidepressant used, type of surgery, interaction with drugs commonly used in the perioperative, risk of withdrawal symptoms, relapse of psychiatric disease and suicide risk, so decision should be made between surgeons, anesthesiologists and psychiatrists, in order to design a safe management plan for the patient who undergo surgery.

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder. .

Effects of Eldepryl on TH and GDNF expressions in substantia nigra and striatum in Parkinson’s disease model in rat / 天津医药

Objective To observe the effects of Eldepryl on expressions of tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) in substantia nigra and striatum in Parkinson’s disease (PD) and to explore the protective mechanism of Eldepryl on dopaminergic neuron . Methods Healthy male Sprague-Dawley (SD) rats (n=72) were randomly divided into control group, model group and Eldepryl group (n=24 in each group). Each group was divided random?ly into 2 subgroups as 4 day treatment group and 8 day treatment group (n=12 in each subgrop). Pakinson’s disease model was established by injecting rotenone subcutaneously back the neck, rats in the control group were injected with an equal vol?ume of sunflower oil subcutaneously at the same location. Rats in the Eldepryl group were then given Eldepryl 0.5 mg·kg-1 in?tragastrically every day for 4 or 8 consecutive days and rats in model group and control group were given an equal volume of saline instead. The expression of TH and GDNF in substantia nigra and striatum were detected by immunohistochemistry and Western blotting. Results Immunohistochemistry and Western blotting showed that strong expression of TH positive cells with little expression of GDNF positive cells were seen in substantia nigra and striatum in rats of control group, and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within control group. The expression of TH cells and GDNF were both significantly reduced in model group compared with those in control group (both P<0.05), and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within each group. The ex?pression of TH positive cells were significantly reduced in Eldepryl group compared with those in control group, and were sig?nificantly increased compared with those in model group. The expression of GDNF positive cells were significantly increased in Eldepryl group compared with those in control group and model group (all P<0.05). And there were significantly more ex?pression of TH positive cells and GDNF positive cells at subgroup of 8 day treatment compared with those at subgroup of 4 day treatment within Eldepryl group with (all P<0.05). Conclusion These data suggest that Eldepryl can protect the dam?age of dopaminergic neurons in substantia nigra and striatum of PD rats. And its therapeutic mechanism may be associated with increased expression of GDNF.

Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1, 5-a][1, 3, 5]triazine

This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.

Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfil neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI50: 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B.

Monoamine Oxidase Inhibitors Attenuate Cytotoxicity of 1-Methyl-4-phenylpyridinium by Suppressing Mitochondrial Permeability Transition

Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (non-selective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with 500 micrometer MPP+. The MAO inhibitors at 10 micrometer revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of MPP+ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.