Demethylenetetrahydroberberine protects dopaminergic neurons in a mouse model of Parkinson's disease / 中国天然药物

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1β and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.

Between the foreign and the local: French midwifery, traditional practitioners, and vernacular medical knowledge about childbirth in Lima, Peru / Entre o estrangeiro e o local: obstetrizes francesas, médicos tradicionais e conhecimento médico vernáculo sobre partos em Lima, Peru

This article examines the politics of midwifery and the persecution of untitled female assistants in childbirth in early republican Peru. A close reading of late colonial publications and the works of Benita Paulina Cadeau Fessel, a French obstetriz director of a midwifery school in Lima, demonstrates both trans-Atlantic and local influences in the campaign against untitled midwives. Cadeau Fessel's efforts to promote midwifery built upon debates among writers in Peru's enlightened press, who vilified untrained midwives' and wet nurses' vernacular medical knowledge and associated them with Lima's underclass. One cannot understand the transfer of French knowledge about professional midwifery to Peru without reference to the social, political, and cultural context.

Este artigo analisa as políticas de práticas de parteiras profissionais e a condenação de parteiras leigas nos primórdios do Peru republicano. A leitura atenta de publicações de fins do período colonial e dos trabalhos de Benita Paulina Cadeau Fessel, obstetriz francesa diretora de uma escola de parteiras em Lima, revela influência tanto transatlântica como local na campanha contra as parteiras sem titulação. Cadeau Fessel promovia seu ofício com base em debates veiculados na imprensa peruana ilustrada, que aviltavam o conhecimento tradicional de amas de leite e parteiras leigas e as associavam às classes desfavorecidas. Só é possível compreender a transferência do conhecimento francês sobre trabalho de parteiras profissionais para o Peru relacionando-a ao contexto social, político e cultural.

Heptachlor induced nigral dopaminergic neuronal loss and Parkinsonism-like movement deficits in mice

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo.

Síndrome de opsoclonia-mioclonia-ataxia em paciente com AIDS / Opsoclonus-myoclonus-ataxia syndrome in an AIDS patient

É relatado aqui o caso de uma mulher de 38 anos com AIDS que desenvolveu a síndrome de opsoclonia-mioclonia-ataxia em um período diferente dos outros casos já relatados na literatura. A síndrome de opsoclonia-mioclonia-ataxia já tinha sido relatada como manifestação inicial de AIDS, assim como no momento da soroconversão de HIV e na síndrome de reconstituição imune. Este caso é único, uma vez que a paciente tinha contagem elevada de CD4 e carga viral negativa no momento em que a síndrome de opsoclonia-mioclonia-ataxia ocorreu.

We report the case of a 38-year-old woman with AIDS who developed opsoclonus-myoclonus-ataxia syndrome during a period different from other cases reported in literature. Opsoclonus-myoclonus-ataxia syndrome had already been reported as the initial neurological presentation of AIDS, as well as at the time of HIV-seroconversion and immune reconstitution syndrome. Our case is unique since the patient had an elevated CD4 count and negative viral load in the period when the opsoclonus-myoclonus-ataxia syndrome occurred.

Effect of epigallocatechin-3-gallate on inflammatory mediators release in LPS-induced Parkinson's disease in rats.

Degeneration of dopamine (DA)-containing neurons in the substantia nigra of the midbrain causes Parkinson's disease (PD). Although neuroinflammatory response of the brain has long been speculated to play a role in the pathogenesis of this neurological disorder, the mechanism is still poorly understood. The aim of the present study was to examine the effect of epigallocatechin-3-gallate (EGCG) in prevention of inflammatory mediators release and protection of dopaminergic neurons from lipopolysaccharide (LPS)-induced neurotoxicity. A single intraperitoneal injection of LPS (15 mg/kg) in male Sprague Dawley rats resulted in an increase of midbrain content of TNF-α, NO and a decrease of DA level at 4, 24 h, 3 and 7 days compared to the control. In addition, LPS reduced the number and the density of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the midbrain at 7 days. Pretreatment with EGCG (10 mg/kg) 24 h before LPS for 7 days decreased TNF-α and NO compared to LPS-treated rats. Moreover, it increased DA level and preserved the number and the density of TH-ir neurons compared to LPS group. In conclusion, EGCG was found to have a potential therapeutic effect against LPS-induced neurotoxicity via reducing TNF-α and NO inflammatory mediators and preserving DA level in midbrain.

Occupational Neurological Disorders in Korea

The purpose of this article was to provide a literature review of occupational neurological disorders and related research in Korea, focusing on chemical hazards. We reviewed occupational neurological disorders investigated by the Occupational Safety and Health Research Institute of Korean Occupational Safety and Health Agency between 1992 and 2009, categorizing them as neurological disorders of the central nervous system (CNS), of the peripheral nervous system (PNS) or as neurodegenerative disorders. We also examined peer-reviewed journal articles related to neurotoxicology, published from 1984 to 2009. Outbreaks of occupational neurological disorder of the CNS due to inorganic mercury and carbon disulfide poisoning had helped prompt the development of the occupational safety and health system of Korea. Other major neurological disorders of the CNS included methyl bromide intoxication and chronic toxic encephalopathy. Most of the PNS disorders were n-hexane-induced peripheral neuritis, reported from the electronics industry. Reports of manganese-induced Parkinsonism resulted in the introduction of neuroimaging techniques to occupational medicine. Since the late 1990s, the direction of research has been moving toward degenerative disorder and early effect of neurotoxicity. To understand the early effects of neurotoxic chemicals in the preclinical stage, more follow-up studies of a longer duration are necessary.

Evaluation of the role of striatal cannabinoid CB[1] receptors on movement activity of parkinsonian rats induced by reserpine

It has been observed cannabinoid CB[1] receptor signaling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson's disease [PD] patients. These evidences suggest that the blocking of cannabinoid CB[1] receptors might be beneficial to improve movement disorders as a sign of PD. In this study, a dose-response study of the effects of intrastriatal injection of a cannabinoid CB[1] receptor antagonist, AM251 and agonist, ACPA, on movement activity was performed by measuring the catalepsy of reserpinized and non-PD [normal] rats with bar test. Also the effect of co-administration the most effective dose of AM251 and several doses of ACPA were assessed. AM251 decreases the reserpine induced catalepsy in dose dependent manner and ACPA causes catalepsy in normal rats in dose dependant manner as well. AM251 significantly reverse the cataleptic effect in all three groups [1, 10, 100ng/rat] that received ACPA. These results support this theory that cannabinoid CB[1] receptor antagonists might be useful to alleviate movement disorder in PD. Also continuance of ACPA induced catalepsy in induced catalepsy. Based on the present finding there is an incomplete overlapping between cannabinoid CB[1] receptor agonist and antagonist effects

Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in mice.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons, however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs for Parkinsonism. Administration of haloperidol (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced catalepsy. The results indicate that BR-16A or ashwagandha has protective effect against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A could be used in preventing the drug-induced extrapyramidal side effects and may offer a new therapeutic approach to the treatment of Parkinson's disease.

¿Es el reflejo glabelar un componente del parkinsonismo nducido por neurolépticos? / Is the glabellar reflex a component of neuroleptic-induced parkinsonism?

Introducción. La evidencia disponible sugiere que algunos signos neurológicos atribuidos al uso de neurolépticos son realmente manifestaciones secundarias de trastornos psicóticos. Objetivo. Se efectuó el presente estudio con el objetivo de evaluar el papel del signo glabelar como componente clínico del parkinsonismo secundario inducido por neurolépticos. Materiales y métodos. Se evaluó un grupo de pacientes con parkinsonismo secundario inducido por neurolépticos, utilizando la escala de Simpson y Angus para efectos colaterales extrapiramidales. La contribución del signo glabelar en el síndrome global se evaluó mediante técnicas de análisis factorial. Resultados. Se evaluaron 103 pacientes, de los cuales, 52 por ciento correspondía a mujeres, con parkinsonismo secundario inducido por neurolépticos. La mayoría de pacientes recibieron haloperidol como tratamiento antipsicótico. Los diagnósticos más frecuentes fueron los trastornos afectivos y los esquizofrénicos. El ítem correspondiente al reflejo glabelar mostró el promedio de covarianza interítem más alto y el mayor valor de unicidad. Los puntajes de alfa de Cronbach de la escala aumentaron al retirar de ésta el ítem correspondiente al signo glabelar. Conclusión. Nuestros hallazgos sugieren que el signo glabelar mide una condición diferente del parkinsonismo secundario inducido por neurolépticos. Sugerimos que este hallazgo clínico no sea utilizado para medir la evolución de la respuesta neurológica a los antipsicóticos

Parkinsonism and other movement disorders in outpatients in chronic use of cinnarizine and flunarizine

O objetivo deste estudo foi determinar a prevalência e os padrões de distúrbios do movimento (DM) em pacientes ambulatoriais sob uso crônico de cinarizina (cz) ou flunarizina (fz), além de estabelecer os principais fatores de risco para o seu aparecimento. Durante três meses foram coletados dados de pacientes ambulatoriais em uso de cz ou fz. Todos esses pacientes foram submetidos a protocolo pré-estabelecido que incluía critérios diagnósticos do DSM-IV para distúrbios do movimento induzido por drogas e critérios para diagnostico de depressão maior. Parkinsonismo (PK) puro foi diagnosticado em 34% dos pacientes, PK com acatisia, PK com acatisia e síndrome mastigatória bucolingual (SMBL), SMBL isoladamente e distonia, foram encontrados em 4% dos pacientes. Os pacientes com SMBL apresentavam a média de idade mais avançada, o maior tempo médio de uso das drogas, configurando-se o grupo de maior risco ao aparecimento dos DM. O grupo dos pacientes com DM apresentou maior incidência de depressão quando comparados com os não afetados. O estudo demonstra uma relação direta entre o tempo de uso da droga, a idade avançada do paciente e o surgimento dos DM. Os resultados também sugerem que estas drogas aumentam a incidência de depressão.

effect of khat on chlorpromazine-induced parkinsonian like movements with some concomitant biochemical changes in rabbits

The aim of the study was to examine the effect of khat on parkinsonian movements induced by a dopamine antagonist chlorpromazine and the effect on some biochemical parameters in rabbits, since chlorpromazine blocks dopamine receptors while khat is known to release catecholamines specially dopamine. Rabbits were divided into five groups. The first group as a control, the second group received only diazepam, the third group received only chlorpromazine, the fourth group received khat orally for three weeks and then injected with diazepam; the fifth and last group received khat orally for three weeks and then injected with chlorpromazine. Parkinsonian-like movements: bradykinesia, rigidity and tremor were observed in all groups. Serum triglyceride and fasting blood sugar were measured as indicators for sympathetic activity. Khat has shown to aggravate Parkinsonian movements induced by chlorpromazine. Diazepam administered to a khat-fed rabbits produced Parkinsonian movements lesser than the group that received chlorpromazine and khat. The serum triglyceride and fasting blood sugar were also measured, and the khat-fed rabbits showed lower levels of serum triglyceride and higher leve1s of fasting blood sugar comparing to the khat-free groups