ABSTRACT
Introduction It is well known that Parkinson’s disease is related to a deficit of dopamine (DA) in the region of the brain called the corpus striatum. The aim of this work is to demonstrate the possibility of in vitro closed-loop control of the DA concentration levels. Methods By applying the electrochemical technique of fast scan cyclic voltammetry (FSCV), the measured values were compared with previously selected ones, and the system made decisions to control infusion pumps by dynamically adjusting the DA concentration in a continuous flow injection cell. Low-cost hardware was used for the acquisition and control signals (Arduino board), whereas for processing the collected data, graphical programming software (LabView) was used. Results The resolution of the system was approximately 0.4 µmol/L, with a time correction of the concentration adjustable between 1 and 90 seconds. The system allowed control of the DA concentration between 1 and 10 µmol/L with an error of approximately +/– 0.8 µmol/L. Conclusion Although designed to control the DA concentration, the system could be used to control, within the range of the developed FSCV, the concentration of other substances or to turn on brain stimulators. These results encourage the possibility of using the system in clinical studies (in vivo).
ABSTRACT
PURPOSE: To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). METHODS: This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. RESULTS: Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3) patients in the felodipine group and in 38/51 (74.5) in the nifedipine group (NS). Side effects, occured in approximately 15 of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. CONCLUSION: Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.
Objetivo - Comparar a eficácia e a tolerabilidade da felodipina-ER com a nifedipina-OROS, ambas em dose diária única, no tratamento da hipertensão arterial (HA) leve e moderada, não complicada. Métodos - Estudo multicêntrico, aberto, randomizado e paralelo, incluindo 121 pacientes com HA essencial e nível de pressão arterial diastólica (PAD) >95 e <110mmHg, sem medicação anti-hipertensiva. Após período de 2 semanas de placebo, os pacientes foram randomizados para receber felodipina-ER, 5mg uma vez ao dia, ou nifedipina-OROS, 30mg uma vez ao dia, durante 4 semanas. As medidas da freqüência cardíaca e da pressão arterial (PA) foram sempre registradas cerca de 24h após a última dose. Exames laboratoriais e eletrocardiograma (ECG) foram realizados ao início e ao final do tratamento. Resultados - Completaram o estudo 111 pacientes, 60 no grupo felodipina e 51 no grupo nifedipina. Em comparação com os valores basais, as médias da PA sistólica e da PAD reduziram-se de 162,5±14,3mmHg e de 102,2±5,1mmHg para 143,3±14,6 e 87,9±7,2mmHg, respectivamente, ao final do tratamento, no grupo felodipina; e de 160,5±16,3mmHg e 902,5±6,2mmHg para 136,1±14,2 e 86,7±7,0mmHg, respectivamente, no grupo nifedipina (p< 0,001 para todas as diferenças). Resposta adequada da PA ao tratamento (normalização da PAD ou redução >10mmHg) ocorreu em 47/60 (78,3%) pacientes do grupo felodipina e em 38/51 (74,5%) do grupo nifedipina (NS). Efeitos colaterais, ocorreram em aproximadamente 15% dos casos, com padrão similar em ambos os grupos. Foram em geral moderados e transitórios, porém responsáveis pelo abandono do tratamento em 2 casos do grupo felodipina e em 3 do grupo nifedipina. Conclusão - Felodipina-ER e nifedipina-OROS, foram igualmente eficazes no tratamento da HA leve e moderada, com bom e similar perfil de tolerabilidade
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Nifedipine , Felodipine , Hypertension/drug therapy , Nifedipine , Felodipine , Drug Tolerance , Analysis of Variance , Chi-Square Distribution , Heart Rate/drug effectsABSTRACT
The effects of the ethanolic extract from the Brazilian toxic plant Pseudocalymma elegans (Veil.) Kuhlm. upon the behavior of mice were studied. Mice that received 1.6 to 3 g/kg of body weight extract presented seizure-like signs dying with a mean latency of 8 min. The LD50 in this situation was estimated in 1.8 g/kg. Mice that received extract 1 g/kg i.p. were observed in an open field 30 min later, presented a decrease in the number of rearings and an increase in the freezing time, without significant differences in the number of crossings, grooming time or number of fecal boluses compared to the control group. Mice submitted to the same treatment and tested on the elevated plus-maze presented a reduction in the percentage of entries and in the time spent in the open arms of the maze. These animals reduced the locomotor activity measured automatically and presented no difference in the muscular tonus, measured by the time of permanence hanging from a wire. These data suggest that the plant extract has compounds with stimulant effects upon the central nervous system: In a lower dose (1 g/kg) we observed behavioral effects that suggest an anxiogenic action of the extract without affecting the muscular tonus, and higher doses resulted in convulsions and death.
Os efeitos do extrato etanólico da planta tóxica Pseudocalymma elegans (Vell.) Kuhlm. sobre o comportamento de camundongos foi estudado. Camundongos que receberam injeções intraperitoneais (i.p.), nas doses de 1.6 a 3 g/kg de peso corporal, apresentaram convulsões e morreram com uma latência média de 8 min. A LD50 foi estimada em 1.8 g/kg. Os camundongos que receberam 1 g/kg (i.p.) do extrato apresentaram um maior número de rearings e um maior tempo de freezing do que o grupo controle, quando observados em um campo aberto 30 min após a injeção. Durante o tempo em que esses animais foram observados no campo aberto não ocorreram alterações significativas no número de cruzamentos, tempo de grooming e número de bolos fecais. Quando esses animais foram colocados em um labirinto em cruz elevado exploraram menos os braços abertos do labirinto que os animais controle; apresentaram uma menor porcentagem de entradas e uma menor porcentagem de tempo de permanência nos braços abertos do labirinto. Esses animais apresentaram também uma menor atividade locomotora medida de forma automatizada e nenhuma alteração no tônus muscular, avaliado pelo tempo de permanência em um arame esticado. Os três primeiros testes sugerem que a administração de doses moderadas do extrato desencadeia um efeito ansiogênico contrário ao observado com a administração de ansiolíticos depressores do sistema ne