Effects of carvacrol and physical exercise on motor and memory impairments associated with Parkinson's disease / Efeitos do carvacrol e do exercício físico sobre o comprometimento motor e de memória associados à doença de Parkinson

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.

Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease / O tratamento com carvacrol melhora a memória de esquiva passiva em um modelo da doença de Parkinson em ratos

ABSTRACT The present study investigated the effects of carvacrol on motor and memory deficits as well as hyperalgesia in the 6-OHDA-lesioned rat model of Parkinson's disease. The animals were subjected to unilateral microinjection of 6-OHDA into the medial forebrain bundle and treated with carvacrol (25, 50 and 100 mg/kg, ip) for six weeks after surgery. The 6-OHDA-lesioned rats showed contralateral rotations towards the lesion side, which was accompanied by learning and memory deficits in a passive avoidance test and a decrease in tail withdrawal latency in a tail flick test at the end of week 6. The results also showed that treatment with carvacrol at a dose of 25 mg/kg ameliorated memory deficits, with no effect on rotations and hyperalgesia in lesioned rats. In conclusion, carvacrol improves memory impairments in rats with Parkinson's disease; therefore, it may serve as an adjunct therapy for the alleviation of memory deficits in Parkinson's disease patients.

RESUMO O presente estudo investigou os efeitos do carvacrol nos déficits motores e de memória, bem como na hiperalgesia, em um modelo da doença de Parkinson (DP) em ratos com lesões 6-OHDA. Os animais foram submetidos a microinjeção unilateral de 6-OHDA no feixe mediano do prosencéfalo e tratados com carvacrol (25, 50 e 100 mg / kg, ip) durante 6 semanas após a cirurgia. Os ratos com lesões 6-OHDA mostraram rotações contralaterais para o lado da lesão, que foram acompanhadas de déficits de aprendizagem e de memória em um teste de evitação passiva, e de uma diminuição da latência de retirada da cauda em um teste de cauda no final da semana 6. Os resultados também mostraram que o tratamento crônico com carvacrol a uma dose de 25 mg / kg aliviou os déficits de memória, sem efeito sobre rotações e hiperalgesia em ratos lesados. Em conclusão, o carvacrol melhora a deficiência de memória em ratos com DP e, portanto, pode servir como uma terapia complementar para aliviar os déficits de memória em pacientes com DP.

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats / Timoquinona protegeu contra deficiências de aprendizagem e memória e danos nos tecidos cerebrais em ratos hipotireoidais juvenis

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

Chronic administration of rosa canina hydro-alcoholic extract attenuates depressive-like behavior and recognition memory impairment in diabetic mice: a possible role of oxidative stress

Objective: This study was designed to evaluate whether chronic Rosa canina [RC] extract administration could improve recognition memory and depressive-like behavior in diabetic mice

Materials and Methods: Seventy-five male albino mice [25-30 g] were randomly divided into 5 groups [15 in each group]

A single intraperitoneal injection of 200 nng/ kg streptozotocin [STZ] was administered to the mice to induce diabetes

The control group received normal saline, and the diabetic groups received normal saline or 50, 250, and 500 mg/kg of RC extract for 28 days

The mice were weighed each week

Recognition memory and depressive-like behavior were assessed using forced swimming and novel object recognition [NOR] tests, respectively. Malondi-aldehyde [MDA] levels and total antioxidant capacity [TAG]were measured in the mouse brain homogenate to evaluate oxidative stress. Statistical analysis was conducted using SPSS, version 22

Results: The groups receiving 250 or 500 mg/kg RC had significantly lower immobility time [159.4 +/- 4.7 and 150.1 +/- 3.1 s] compared to the sham control group [192.1 +/- 7.8 s] in the forced swimming test, and a higher discrimination index [0.39 +/- 0.02 and 0.48 +/- 0.03] was seen in diabetic animals in the NOR task compared to the sham control group [0.2 +/- 0.01]

Also, the groups receiving treatment with RC [250 and 500 mg/kg] had significantly higher TAG [0.92 +/- 0.04 and 0.96 +/- 0.05 mmol/L] and lower MDA [0.76 +/- 0.02 and 0.67 +/- 0.03 nmol/mg protein] levels in the brains in comparison to the model group. In the 3rd and 4th weeks of study, the RC-treated mice [250 and 500 mg/kg] gained more weight [31.2 +/- 0.3 and 32.4 +/- 0.3 g, and 31.3 +/- 0.2 and 33.7 +/- 0.3 g, respectively] than the diabetic group [30 +/- 0.2 and 29.6 +/- 0.3 g]

Conc/us/on:This study showed that RG attenuated impairment of recognition memory and depressive-like behavior probably through modulation of oxidative stress in an STZ model of diabetes in mouse brains

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

PURPOSE: To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35-treated mice. METHODS: PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method. RESULTS: Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function. CONCLUSION: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response in Alzheimer's disease in animals.

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Effect of human chorionic gonadotropin and vitamine E on cellular density of CA1 hippocampal area, learning ability and memory, following ischemia - reperfusion injury in mice

Reduction in cerebral blood flow following cereblal ischemia cause the production of oxygen free radicals and finally leads to brain tissue destruction. Pyramidal cells of the CA1 region of hippocampus are highly sensitive to hypoxic condition. This study was done to determine the effect of human chorionic gonadotropin [hCG] and vitamine E on cellular density of CA1 hippocampal area, learning ability and memory, following ischemia - reperfusion injury in mice. This experimental study was done on 40 male mice in 5 groups as follow: sham control, ischemia, hCG treated, vitamine E treated and hCG + vitamine E treated groups. Single dose of vitamin E was injected intraperitonaly during the establishment of reperfusion and hCG was injected from 48h after ischemia for 5 days. Folowing the treatment period, mice brains were fixated by transcardial perfusion and stained by nissle method. The shuttle box was used to evaluate the learning memory. Co-administartion of vitamine E and hCG, significantly increased the cell numbers in hippocampus compared to the ischemic group [P<0.001]. Also learning and memory improved in treatment group in comparison with ischemia group [P<0.05]. Co-administration of vitamin E and hCG improved ischemia-induced neurodegenration and memory impairment

[Protective effect of Co-enzyme Q10 on seizure, short term spatial memory and oxidative stress in induced-epileptic rats]

Temporal lobe epilepsy is the most common type of epilepsy in human. Patients suffer from spontaneous seizures and memory deficiency. This study was done to assess the effect of Co-enzyme Q10 [CoQ10] administration on seizure, short-term spatial memory and stress oxidative indices in hippocampus of kainic acid-induced epilepsy. In this experimental study, 48 male rats were randomly allocated into six groups: shamoperated; CoQ10 [10 mg/kg/bw]-treated SH; kainate; CoQ10 [2, 5 and 10 mg/kg/bw] treated kainic acid. CoQ10 was intraperitoneally administered daily for one week before intra-hippocampal injection of kainic acid [4microg/kg/bw] in animals. Kainic acid induced chronic and acute spontaneous seizures in animals. Also, kainic acid administration caused a reduction in alternational behavior rate [consecutive or serially entrance into all of arms in triplet set], increasing of malondialdehide, nitrite level and decreasing of superoxide dismutase activity compared to sham group [P<0.05]. Pre-treatment of kainate rats with CoQ10 decreased rate of spontaneous seizures [P<0.05]. CoQ10 increased alternational behavior rate, decreased malondialdehide and nitrite serum level [P<0.05]. But it had no significant effect on superoxide dismutase activity. Pre-treatment of kainic acid exposed rats with CoQ10 reduced rate of seizures and improved short-term spatial memory and oxidative stress indices in rats

Phytoestrogen -zearalanol ameliorates memory impairment and neuronal DNA oxidation in ovariectomized mice

OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency. .

Ginkgo biloba e memória: revisão sistemática / Ginkgo biloba and memory: systematic review

Com o envelhecimento da população, os distúrbios de memória têm-se tornado patologias cada vez mais frequentes. Com exceção de uma minoria dos casos cujas causas são reversíveis, estas doenças possuem prognóstico desanimador, curso inexorável e opções terapêuticas muito limitadas. O medicamento fitoterápico mais frequentemente utilizado para distúrbios de memória é o extrato seco de ginkgo biloba (GB). Suas ações antioxidantes, antiagregantes e vasodilatadoras têm encorajado diversos profissionais a utilizarem-no neste tratamento, porém não há registros convincentes que comprovem a eficácia do uso desta substância para tal fim. Objetivos: Avaliar a eficácia do GB na prevenção e no tratamento de distúrbios de memória. Métodos: Revisão sistemática da literatura dos últimos dez anos dos estudos clínicos duplo-cegos, randomizados, placebo-controlados, publicados na língua inglesa. Resultados e Conclusões: Embora tenhamos obtido poucos ensaios controlados sobre o tema, não há evidências suficientes para se indicar o uso da droga com a finalidade de tratar e/ou prevenir distúrbios de memória.

Comporación de dos formulaciones de nimodipina en pacientes de edad avanzada con deterioro cognitivo estudio multicéntrico nacional aleatorizado doble ciego / Comporación two nimodipine formulations in elderly patients with cognitive impairment randomized national multicentre double-blind

Evaluar la seguridad y la efectividad en deterioro cognitivo de pacientes con edades entre 55 a 80 años de dos formulaciones de nimodipina: 120 mg de liberación programada (LP) una toma diaria y nimodipina 30 mg de liberación inmediata (LI), 4 tomas diarias. Estudio doble ciego, doble simulado, aleatorio, con pacientes con MMST entre 15 y 24. Estos recibieron las 4 semanas iniciales placebo, luego 12 semanas doble ciego, nimodipina LI activo cuatro tomas diaria, o nimodipina LP activo en una toma diaria. Fueron evaluados a las 12 semanas de tratamiento mediante MMST, escala de Barthel, impresión clínica de cambio" por el médico y el paciente. Ingresaron 69 pacientes, finalizaron el 95.6 por ciento. Treinta y tres con nimodipina LP y treinta y tres con nimodipina LI. Con nimodipina LI, 79 por ciento mejoraron el score de MMST; 78 por ciento notaron mejoría y en 84 por ciento la mejoría fue observada por el médico. Cinco pacientes presentaron reacciones adversas (lipotimia, dos con erupción cutánea, cefalea y epigastralgia), dos suspendieron el tratamiento. En nimodipina LP, 94 por ciento mejoraron el MMST, 94 por ciento dijeron sentirse mejor y en el 91 por ciento, la mejoría fue observada por el médico. Tres (3) pacientes presentaron reacciones adversas (acidez gástrica, hipotensión y mareos), uno suspendió el tratamiento. La nimodipina 120 mg. LP administrada una vez al día y la nimodipina LI 30 mg. administrada cuatro veces al día mejoran el deterioro cognitivo en la edad avanzada, siendo bien toleradas.

Efectividad y tolerabilidad de la citicolina (somazina®): en el tratameinto de pacientes con deterioro cognitivo tipo demencia / Effectiveness and tolerabilidad of the citicolina (somazina®) in the treatment of patient with deterioration cognitivo type insanity

Evaluar la citicolina administrada a dosis de 1000 mg diarios durante 12 semanas en pacientes con criterios de demencia según Mini Mental State Test. (MMST) < 24 puntos, con el fin de observar los cambios en el MMST y en la calidad de vida. Se realizó un estudio, fase IV, prospectivo, abierto, multicéntrico, donde incluyeron pacientes de ambos sexos con edades comprendidas entre 45 y 85 años con deterioro de la función mental por: deterioro mental del anciano o trastornos vasculares crónicos, con un Score en MMST entre 12 y 23, a los cuales se suministró Citicolina (CDP.colina) en gotas a una dosis de 1000 mg., 10 cc (2 cucharaditas) diarias durante 3 meses. La efectividad fue evaluada mediante los cambios en los scores de: Mini Mental State Test, Escala de Calidad de Vida de Barthel, opinión del paciente o cuidador, opinión del médico a los tiempos: 0 días; 1,5 y 3 meses de tratamiento. Ingresaron al estudio 55 pacientes. La mayoría tomaban otro tipo de medicamentos y estos se mantuvieron sin cambios desde el inicio hasta el final del estudio. Se presentó un descenso discreto en las presiones arteriales sistólicas en ambas posiciones y en la presión arterial diastólica en la posición sentada entre el inicio y la 6ta semana sin modificaciones posteriores. Hubo un incremento importante en los promedios del MMST, el 92 por ciento de los pacientes mejoraron los resultados, en el 32 por ciento el cambio fue mayor de 5 puntos y el 18 por ciento tuvo resultados normales al final. Dos de tres pacientes con demencia severa pasaron a demencia moderada (10 a 16 ptos y 10 a 15 ptos). Diez de diecinueve pasaron de demencia moderada a leve y nueve pacientes pasaron de demencia moderada a un puntaje normal. Siete pacientes presentaron efectos adversos: mareos, inquietud, náuseas, diarrea, insomnio, epigastralgia, empeoramiento motor, ira, dos pacientes suspendieron (mareos, ataques de ira) y dos necesitaron tratamiento (mareos: cimnarizina; ira: alprazolan).

Insulin therapy--role beyond glucose control.

Larger studies had shown improved patient outcome and lower probability of coronary artery disease in insulin treated groups. The classical lipid abnormalities associated with type 2 diabetes are low HDL-cholesterol concentration and high triglyceride concentration. Insulin usage leads to a decrease in triglyceride concentration, primarily by its effect on the enzyme adipose tissue lipoprotein lipase. Insulin suppresses the enzyme, thereby controlling lipolysis in uncontrolled diabetes. Insulins therapy also improves the endothelial dysfunction especially in people with evident macrovascular complications. Though insulin is noted to increase adrenergic tone and may cause elevation of blood pressure, still patients with insulinoma do not have high blood pressure. Some studies suggest weight gain with insulin therapy, others contradict it. One study suggests that insulin does not affect treatment satisfaction. Insulin is known to improve the glycaemic scenario and also the insulin secretory pattern by reducing the glucotoxicity.

Treatment of memory impairment, vertigo and tinnitus in the elderly with piribedil in an Indian general practice setting.

Age-related dopamine decline leads to memory impairment, vertigo or tinnitus leading to a reduced quality of life in the elderly. This study demonstrates the efficacy and acceptability of piribedil, a dopamine agonist, in improving these conditions. Of the 515 patients included in the study, there was complete resolution of memory impairment, vertigo and tinnitus in 103 patients (20%), improvement in 374 cases (72.6%), with 38 cases (7.4%) showing no change after one month's treatment with piribedil. The treatment was well accepted with a low frequency of side-effects and full compliance with daily medication.

Ginkgo biloba e memória: mito ou realidade? / Ginkgo biloba and memory: myth or reality?

O uso dos extratos de Ginkgo biloba para tratamento e prevençãode afecções relacionadas ao envelhecimento e, particularmente, de transtornos da memória baseia-se em práticas médicas ancestrais e estende-se largamente nos dias de hoje. Contudo, a literatura médica carece de estudos sistemáticos sobre a eficácia de seus princípios ativos no tratamento das demências e da doença de Alzheimer. Em virtude do uso muitas vezes indiscriminado desses produtos, além da falta de um controle adequado sobre sua produção e comercialização, a prescrição da Ginkgo biloba nos transtornos de memória foi questionada nos últimos anos pelos seguidores da boa prática clínica. O presente estudo revê criticamente a literatura médica relevante ao emprego dessas substâncias na doença de Alzheimer e outros transtornos da memória, bem como os subsídios científicos para os supostos efeitos neuroprotetores da Ginkgo biloba.

Manejo farmacológico de algunos problemas asociados al trauma craneo-encefálico / Pharmacological management of several dysfunctions related to traumatic brain injury

El presente trabajo constituye una recopilación de los avances en el manejo farmacológico de varias disfunciones asociadas al traumatismo cerebral, en la fase sub-aguda de recuperación. Se ofrecen varias alternativas de tratamiento, debiendo considerarse una guía para el manejo terapéutico de pacientes con secuelas de trauma cráneo-encefálico en la etapa subaguda de rehabilitación

Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-_-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor

Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.