RESUMO
Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve which leads to retinal ganglion cell (RGC) loss, and visual dysfunction. We investigated the ability of a single microinjection of bacterial lipopolysaccharide (LPS) directly into the optic nerve to induce functional and structural alterations compatible with ON. For this purpose, optic nerves from male Wistar rats remained intact or were injected with vehicle or LPS. The effect of LPS was evaluated at several time points post-injection in terms of: i) visual pathway and retinal function (visual evoked potentials (VEPs) and electroretinograms, (ERGs), respectively), ii) anterograde transport from the retina to its projection areas, iii) consensual pupil light reflex (PLR), iv) optic nerve histology, v) microglia/macrophage reactivity (by Iba-1- and ED1-immunostaining), vi) astrocyte reactivity (by glial fibrillary acid protein-immunostaining), vii) axon number (by toluidine blue staining), vii) demyelination (by myelin basic protein immunoreactivity and luxol fast blue staining), viii) optic nerve ultrastructure, and ix) RGC number (by Brn3a immunoreactivity). LPS induced a significant and persistent decrease in VEP amplitude and PLR, without changes in the ERG. In addition, LPS induced a deficit in anterograde transport, and an early inflammatory response consisting in an increased cellularity, and Iba-1 and ED1-immunoreactivity in the optic nerve, which were followed by changes in axonal density, astrocytosis, demyelination, and axon and RGC loss. These results suggest that the microinjection of LPS into the optic nerve may serve as a new experimental model of primary ON.
Assuntos
Lipopolissacarídeos , Nervo Óptico/patologia , Neurite Óptica/induzido quimicamente , Neurite Óptica/patologia , Animais , Toxina da Cólera/metabolismo , Modelos Animais de Doenças , Eletrorretinografia , Potenciais Evocados Visuais/efeitos dos fármacos , Contagem de Leucócitos , Lipopolissacarídeos/administração & dosagem , Masculino , Microinjeções , Neurite Óptica/líquido cefalorraquidiano , Ratos , Ratos Wistar , Reflexo Pupilar/efeitos dos fármacos , Retina/patologiaRESUMO
The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18-22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26-0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79-0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09-0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lactente , México , GravidezRESUMO
In rats, iron deficiency produces an alteration in myelin formation. However, there is limited information on the effects of this condition on oligodendroglial cell (OLGc) proliferation and maturation. In the present study, we further analyzed the hypomyelination associated with iron deficiency by studying the dynamics of oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron-deficient (4 mg Fe/kg) diets from gestation day 5 until postnatal day 3 (P3) or 11 (P11). OLGc proliferation, migration and differentiation were investigated before and after an intracranial injection of apotransferrin at 3 days of age (P3). The proliferating cell population was evaluated at P3. Iron-deficient (ID) animals showed an increase in the oligodendrocyte precursors cell (OPC) population in comparison with controls. The overall pattern of migration of cells labeled with BrdU was investigated at P11. Iron deficiency increased the amount of BrdU(+) cells in the corpus callosum (CC) and decreased OLGc maturation and myelin formation. Changes in nerve conduction were analyzed by measuring visual evoked potentials. Latency and amplitude were significantly disturbed in ID rats compared with controls. Both parameters were substantially normalized when animals were treated with a single intracranial injection of 350 ng apotransferrin (aTf). The current results give support to the idea that iron deficiency increases the number of proliferating and undifferentiated cells in the CC compared with the control. Treatment with aTf almost completely reverted the effects of iron deficiency, both changing the migration pattern and increasing the number of mature cells in the CC and myelin formation.
Assuntos
Apoproteínas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Deficiências de Ferro , Oligodendroglia/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Transferrina/uso terapêutico , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Apoproteínas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Peso Corporal/fisiologia , Encéfalo , Bromodesoxiuridina/metabolismo , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Corpo Caloso/metabolismo , Corpo Caloso/patologia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/fisiopatologia , Eletroencefalografia/métodos , Potenciais Evocados Visuais/efeitos dos fármacos , Potenciais Evocados Visuais/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hematócrito/métodos , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Oligodendroglia/fisiologia , Estimulação Luminosa/métodos , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ácidos Siálicos/metabolismo , Transferrina/metabolismoRESUMO
Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20% to 25% of the world's infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow-up studies point to long-lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep-waking states and several differences in sleep states organization were reported. Persistent sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA.
Assuntos
Anemia Ferropriva/fisiopatologia , Desenvolvimento Infantil/fisiologia , Deficiências de Ferro , Ferro da Dieta/farmacologia , Fenômenos Fisiológicos do Sistema Nervoso , Estado Nutricional , Anemia Ferropriva/sangue , Pré-Escolar , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/efeitos dos fármacos , Potenciais Evocados Visuais/fisiologia , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Ferro/sangue , Ferro da Dieta/uso terapêutico , Fenômenos Fisiológicos do Sistema Nervoso/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Transtornos do Sono-VigíliaRESUMO
Contrast sensitivity (CS) was evaluated in 41 former workers from a lamp manufacturing plant who were on disability retirement due to exposure to mercury and 14 age-matched controls. The CS was measured monocularly using the sweep visual evoked potential (sVEP) paradigm at 6 spatial frequencies (0.2, 0.8, 2.0, 4.0, 15.0, and 30 cpd). Statistical difference (p<0.05) was found between the controls and the patient right and left eyes for 2.0 and 4.0 cpd. According the results in those spatial frequencies the eyes were classified in best and worst. Statistical differences were found between the controls and the best eyes for 2.0 and 4.0 cpd and for 0.8, 2.0, and 4.0 cpd for their worst eyes. No correlation was found between CS results and the time of exposure (mean=8.9 yr+/-4.1), time away from the mercury source (mean=6.0 yr+/-3.9), urinary mercury level at the time of work (mean=40.6 microg/g+/-36.3) or with the mercury level at the CS measurement time (mean=1.6 microg/g+/-1.1). We show the first evidence of a permanent impairment in CS measured objectively with the sVEP. Our data complement the previous psychophysical works reporting a diffuse impairment in the CS function showing a CS reduction in the low to middle spatial frequencies. In conclusion, non-reversible CS impairment was found in occupational exposure to mercury vapor. We suggest that CS measurement should be included in studies of the mercury effects of occupational exposure.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Sensibilidades de Contraste/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Intoxicação por Mercúrio/diagnóstico , Mercúrio/toxicidade , Adulto , Estudos de Casos e Controles , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição OcupacionalRESUMO
The early stages of visual information processing, involving the detection and perception of simple visual stimuli, have been demonstrated to be sensitive to psychotropic agents. The present study investigated the effects of an acute dose of bromazepam (3 mg), compared with placebo, on the P100 component of the visual evoked potential and reaction time. The sample, consisting of 14 healthy subjects (6 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs the initial stage of visual information processing, as observed by an increase in P100 latency.
Assuntos
Ansiolíticos/farmacologia , Bromazepam/farmacologia , Potenciais Evocados Visuais/efeitos dos fármacos , Adulto , Análise de Variância , Eletrofisiologia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Placebos , Tempo de Reação/efeitos dos fármacosRESUMO
The early stages of visual information processing, involving the detection and perception of simple visual stimuli, have been demonstrated to be sensitive to psychotropic agents. The present study investigated the effects of an acute dose of bromazepam (3 mg), compared with placebo, on the P100 component of the visual evoked potential and reaction time. The sample, consisting of 14 healthy subjects (6 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs the initial stage of visual information processing, as observed by an increase in P100 latency.
Os estágios iniciais do processamento da informação visual, envolvendo a percepção e detecção de um estímulo visual simples, tem demonstrado serem sensíveis a agentes psicotrópicos. O presente estudo investigou os efeitos de uma dose aguda de bromazepam (3 mg), comparado com placebo, no componente P100 do potencial evocado visual e no tempo de reação. A mostra consistiu de 14 sujeitos sadios (6 homens e 8 mulheres), submetidos a uma tarefa de discriminação visual, a qual empregou o paradigma "oddball". Os resultados sugerem que o bromazepam (3 mg) prejudica o estágio inicial do processamento da informação visual, como observado pelo aumento da latência do P100.
Assuntos
Adulto , Feminino , Humanos , Masculino , Ansiolíticos/farmacologia , Bromazepam/farmacologia , Potenciais Evocados Visuais/efeitos dos fármacos , Análise de Variância , Eletrofisiologia , Potenciais Evocados Visuais/fisiologia , Placebos , Tempo de Reação/efeitos dos fármacosRESUMO
The aim of this study was to compare the effects of barbiturate, benzodiazepine and ketamine on flash-evoked potentials (F-VEP) in adult rabbits. A total of 36 animals were studied, 16 after pentobarbital endovenous (EV) infusion, 10 after midazolam EV administration, and 10 after ketamine EV infusion. Pentobarbital induced triphasic F-VEP, first negative (N1), second positive (P1), third negative (N2) waves, all with large amplitudes and P1 with well-defined morphology. Mean P1 latency was 33ms. Midazolam induced similar but less defined triphasic waves, with mean latency of 27ms. Ketamine induced poliphasic and poorly defined F-VEP, with mean first positive (P1) latency of 27ms. Statistical analysis showed more elongated latency for the pentobarbital group than the midazolam and ketamine groups. The results of this study suggest that the pharmacological effects of pentobarbital and midazolam on GABA neurotransmission in rabbit visual cortex may be different; another neurotransmission system, possibly cholinergic, may be involved. The ketamine effect seen in rabbit visual cortex seems to be different from pentobarbital and midazolam.
Assuntos
Anestésicos Dissociativos/farmacologia , Potenciais Evocados Visuais/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Midazolam/farmacologia , Fenobarbital/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Feminino , Coelhos , Córtex Visual/efeitos dos fármacosRESUMO
Benzodiazepines have been used in the pharmacological treatment of anxiety for over four decades. However, very few studies have combined bromazepam and event-related potentials (ERP). The present study aimed at investigating the modulatory effects of this drug on brain dynamics. Specifically, the effects of bromazepam (3 mg) on the P300 component of the ERP were tested in a double-blind experiment. The sample, consisting of 15 healthy subjects (7 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Electrophysiological (P300) and behavioral measures (stroop, digit span, and reaction time) were analyzed across three experimental conditions: placebo 1, placebo 2, and bromazepam. Results suggest that the effects of bromazepam (3 mg) on cognitive processes are not apparent. In spite of what seems irrefutable in current literature, bromazepam did not produce evident effects on the behavioral and electrophysiological variables analyzed.
Assuntos
Ansiolíticos/farmacologia , Bromazepam/farmacologia , Cognição/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Método Duplo-Cego , Eletrofisiologia , Feminino , Humanos , Masculino , Tempo de Reação/efeitos dos fármacosRESUMO
UNLABELLED: The P300 component of the event-related potential (ERP) is a general measurement of "cognitive efficiency". It is an index of the ability of an individual's central nervous system (CNS) to process incoming information. OBJECTIVE: To compare the neuromodulatory effects of caffeine and bromazepam on the visual ERP (P300), in relation to a P300 normative database. METHOD: 15 right-handed individuals (7 male and 8 female), between 20 and 30 years of age, healthy, free of any cognitive impairment and not making use of psychoactive substances were studied. Participants were submitted to a visual discrimination task, which employed the "oddball" paradigm, after the administration of caffeine and bromazepam, in a randomized, double-blind design. RESULTS: Statistically significant differences were observed when the caffeine and bromazepam conditions were compared to the normative database. CONCLUSION: The present results suggest that caffeine and bromazepam have distinct modulatory effects on CNS functioning.
Assuntos
Bromazepam/farmacologia , Cafeína/farmacologia , Fármacos do Sistema Nervoso Central/farmacologia , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Neurotransmissores/farmacologia , Adulto , Ansiolíticos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
Benzodiazepínicos têm sido utilizados no tratamento farmacológico da ansiedade há mais de quatro décadas. No entanto, poucos estudos têm combinado bromazepam e potencial evocado relacionado a evento (PRE). O presente estudo teve por objetivo investigar os efeitos modulatórios desta droga na dinâmica cerebral. Especificamente, os efeitos de 3mg de bromazepam no componente P300 do PRE foram analisados em um experimento duplo-cego. A amostra consistiu de 15 sujeitos sadios (7 homens e 8 mulheres), submetidos a uma tarefa de discriminação visual utilizando o paradigma "oddball". Medidas eletrofisiológicas (P300) e comportamentais (stroop, digit span, e tempo de reação) foram analisadas em três condições experimentais: placebo 1, placebo 2 e bromazepam. Os resultados sugerem que os efeitos de 3mg de bromazepam em processos cognitivos não são aparentes. Apesar do que parece irrefutável na literatura, o bromazepam não produziu efeitos evidentes nas variáveis comportamentais e eletrofisiológicas analisadas.
Assuntos
Adulto , Feminino , Humanos , Masculino , Ansiolíticos/farmacologia , Bromazepam/farmacologia , Cognição/efeitos dos fármacos , /efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Método Duplo-Cego , Eletrofisiologia , Tempo de Reação/efeitos dos fármacosRESUMO
O componente P300 do potencial evocado relacionado a evento é uma medida geral de "eficiência cognitiva" e um índice da qualidade do processamento e armazenamento de informações pelo sistema nervoso central (SNC). OBJETIVO: Comparar os efeitos neuromoduladores da cafeína e do bromazepam a partir do banco normativo do potencial evocado visual (P300). MÉTODO: 15 sujeitos destros (7 homens e 8 mulheres), entre 20 e 30 anos de idade, sadios, livres de qualquer déficit cognitivo e sem uso de substâncias psicotrópicas ou psicoativas foram estudados. Os sujeitos foram submetidos a uma tarefa de discriminação visual utilizando o paradigma "oddball", após a administração de uma cápsula de cafeína ou de bromazepam, em um desenho duplo-cego randomizado. RESULTADOS: Foram observadas diferenças estatisticamente significativas quando as condições cafeína e bromazepam foram comparadas com o banco normativo. CONCLUSÃO: Os resultados sugerem que a cafeína e o bromazepam têm efeitos moduladores específicos no SNC.
Assuntos
Adulto , Feminino , Humanos , Masculino , Bromazepam/farmacologia , Cafeína/farmacologia , Fármacos do Sistema Nervoso Central/farmacologia , /efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Neurotransmissores/farmacologia , Ansiolíticos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Método Duplo-CegoRESUMO
OBJECTIVE: A decrease in iron concentration is accompanied by alterations in catecholaminergic and GABAergic neurotransmission systems, important in learning, memory and attention. It was hypothesized that iron deficient children would present attention deficits. A visual-event related potentials (ERPs) study is presented using an oddball paradigm in order to determine the P300 in ID children. METHODS: After medical examination, blood was obtained from 201 children for a complete hematological study. Two groups were selected, iron deficient (ID) (serum iron <60 microg/dl) and control (C) (serum iron >60 microg/dl). In both groups ERPs were recorded while executing a continuous performance task (oddball paradigm). Afterwards iron levels were restored in ID children by iron supplementation (ID-IS group) and all tests reapplied. RESULTS: ID children almost lacked a P300 in central and parietal regions. After iron supplementation, P300 clearly became evident although its Pz amplitude remained smaller compared to C children. CONCLUSIONS: A clear and strong correlation was found between ID and attention alterations in children. Iron supplementation nearly brings the P300 to normal levels although it is not known if the P300 difference in Pz is due to other nutritional/environmental deficits or to developmental psychomotor impairments in ID children. SIGNIFICANCE: It has been long known that iron deficient children have cognitive impairments but there is an insufficient number of electrophysiological works allowing to identify the source of this problem. In this work an attention deficit is demonstrated in ID children through a severely reduced P300, which recovers substantially after iron supplementation.
Assuntos
Potenciais Evocados P300/efeitos dos fármacos , Deficiências de Ferro , Ferro da Dieta/uso terapêutico , Comportamento , Contagem de Células Sanguíneas , Criança , Deficiências Nutricionais/sangue , Deficiências Nutricionais/psicologia , Suplementos Nutricionais , Potenciais Evocados Visuais/efeitos dos fármacos , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologiaRESUMO
The stimulant effects of caffeine on cognitive performance have been widely investigated. The visual evoked potential, specially the P300 component, has been used in studies that explain the stimulant mechanisms of caffeine through neurophysiological methods. In this context, the present study aimed to investigate electrophysiological changes (P300 latency) and modification of cognitive and motor performance produced by caffeine. Fifteen healthy volunteers, 9 women and 6 men (26 +/- 5 years, 67 +/- 12.5 kg) were submitted three times to the following procedure: electroencefalographic recording, Word Color Stroop Test, and visual discrimination task. Subjects took a gelatin caffeine capsule (400 mg) or a placebo (P1 and P2), in a randomized, crossover, double-blind design. A one-factor ANOVA and Tukey post hoc test were used to compare dependent variables on the C, P1 and P2 moments. The statistical analyses indicated a non-significant decrease in reaction time, Stroop execution time and latency at Cz on the caffeine moment when compared to the others. Moreover, a non-significant increase in Stroop raw score and latency at Pz could be observed. The only significant result was found at Fz. These findings suggest that the positive tendency of caffeine to improve cognitive performance is probably associated with changes in the frontal cortex, a widely recognized attention area.
Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Análise de Variância , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia , Feminino , Humanos , Masculino , Tempo de Reação/efeitos dos fármacosRESUMO
Os efeitos estimulantes da cafeína no desempenho cognitivo vêm sendo amplamente investigados. O potencial evocado visual (P300) tem sido empregado em estudos recentes que buscam elucidar os mecanismos excitatórios da cafeína através de métodos neurofisiológicos. Neste contexto, o presente estudo objetivou examinar as variações geradas pela cafeína em respostas eletrofisiológicas (latência do P300) e determinar modificações no desempenho cognitivo e motor. Para tanto, 15 indivíduos hígidos, sendo 9 mulheres e 6 homens (26 ± 5 anos, 67 ± 12,5 kg) foram submetidos por três vezes à seguinte rotina: aquisição de sinais eletroencefalográficos, Word Color Stroop Test e tarefa de discriminação visual. Foi administrada uma cápsula gelatinosa de 400 mg de cafeína ou de placebo (P1 e P2) em um desenho randomizado duplo-cego cruzado. Foi empregada a ANOVA com um fator e post hoc de Tukey - HSD para a comparação das variáveis nos momentos C, P1 e P2. O momento cafeína apresentou redução não significativa no tempo de reação, no tempo de execução do Stroop e na latência em Cz. Observou-se também aumento não significativo no escore bruto do Stroop e na latência em Pz. O único resultado significativo encontrado foi na latência em Fz. Assim, pode-se concluir que a tendência favorável à ingestão de cafeína na melhora das respostas cognitivas pode estar relacionada a mudanças em regiões específicas do cérebro, como o córtex frontal, área amplamente relacionada com os processos de atenção.
Assuntos
Humanos , Masculino , Feminino , Adulto , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , /efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia , Tempo de Reação/efeitos dos fármacosRESUMO
Lorazepam has been reported to atypically disrupt visual processing compared to other benzodiazepines (BZs), but it is not known to what extent this effect extends to impairment in other modalities. Our objective was to compare the effects of lorazepam with those of flunitrazepam, a BZ with standard effects, on visual and auditory event-related potentials (ERPs) using the same paradigm. The study followed a placebo-controlled, double-blind, parallel group-design and involved single oral doses of lorazepam (2.0 mg), flunitrazepam (1.2 mg) and placebo. Thirty-six young, healthy subjects completed a test battery before and after treatment including classic behavioural tests, visual and auditory ERPs. Both drugs led to comparable alterations on behavioural tests and double-dissociations were found, indicating that the doses used were equipotent: lorazepam was more deleterious than flunitrazepam and placebo in fragmented shape identification, while simple reaction times were prolonged for flunitrazepam in comparison to lorazepam and placebo. Effects on P3 latencies were also distinct: alterations in both modalities for flunitrazepam were equivalent and greater than placebo's. In contrast, lorazepam at the frontal and central electrode sites led to greater changes in visual than in auditory latency, and also to longer visual latencies than flunitrazepam and placebo, but lorazepam's auditory latency effects were only different to placebo's at the parietal electrode site. Peripheral visual changes were not responsible for these effects. Differences in the impairment profile between equipotent doses of lorazepam and flunitrazepam suggests that lorazepam induces atypical central visual processing changes.
Assuntos
Ansiolíticos/efeitos adversos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Flunitrazepam/efeitos adversos , Lorazepam/efeitos adversos , Adolescente , Adulto , Análise de Variância , Cognição/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Fatores de TempoRESUMO
Evoked potentials provide noninvasive measures of nerve transmission and CNS functioning. Auditory brainstem responses (ABR) and visual evoked potentials (VEP) show dramatic changes in infancy, largely as a result of progressive myelination. Because iron is required for normal myelination, pathway transmission in these sensory systems might be affected by early iron deficiency. We previously reported evidence to that effect: infants with iron-deficiency anemia (IDA) had slower transmission through the auditory brainstem pathway, uncorrected by iron therapy. To determine long-term effects, ABR and/or VEP of healthy Chilean children who were treated for IDA or were nonanemic in infancy were compared at approximately 4 y of age. Absolute latencies for all ABR waves and interpeak latencies (except I-III interval) were significantly longer in former IDA children. Longer latency was also observed for the P100 wave on VEP. The magnitude of differences was large-about 1 SD. These findings, with differences in latencies but not amplitudes, further support the hypothesis that IDA in infancy alters myelination and provide evidence that effects on transmission through the auditory and visual systems can be long lasting. Subtle changes in sensory pathway transmission might be an underlying mechanism for the derailment of other developmental aspects in early IDA.
Assuntos
Anemia Ferropriva/fisiopatologia , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/prevenção & controle , Criança , Pré-Escolar , Eletroencefalografia , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Potenciais Evocados Visuais/efeitos dos fármacos , Potenciais Evocados Visuais/fisiologia , Feminino , Compostos Ferrosos/uso terapêutico , Seguimentos , Idade Gestacional , Humanos , Lactente , Masculino , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Valores de ReferênciaRESUMO
OBJECTIVES: To determine the effect of alpha-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants. STUDY DESIGN: Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life. RESULTS: Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less (p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants. CONCLUSIONS: The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely.