Efeito hipotensor de três formulações diferentes do tartarato de brimonidina em olhos normais / Hypotensive effect of three different formulations of brimonidine tartrate in normal eyes

OBJETIVO: Comparar o efeito hipotensor a curto prazo das três formulações de colírio de tartarato de brimonidina, Alphagan®, Alphagan® P e Alphagan® Z em olhos normais. MÉTODO: Estudo prospectivo, randomizado, duplo-cego que contou com 60 voluntários, os quais foram submetidos a exame oftalmológico inicial e aferição da pressão intraocular (PIO). Os participantes foram distribuídos em três grupos: 1 tartarato de brimonidina 0,15%, 2 tartarato de brimonidina 0,2% e 3 tartarato de brimonidina 0,1%, aleatoriamente, cada um recebeu uma gota de colírio em cada olho e a pressão intraocular foi aferida após 30 minutos, 1 hora e 2 horas. RESULTADOS: Observou-se que todas as concentrações de tartarato de reduziram significativamente a pressão intraocular durante o tempo estudado, com p<0,05. Ao ser analisada a diferença percentual do efeito hipotensor de cada grupo, verificou-se que não há diferença significativa entre os colírios estudados: (1) -13,50%, (2) -11,50%, (3) -11,90% após 30 minutos (p=0,650); (1) -24,30%, (2) -18,60%, (3) -18,30% após 1 hora (p=0,324); (1) -29,14% (2) -21,20%, (3) -25,60% após 2 horas (p=0,068). CONCLUSÃO: Não há diferença estatisticamente significativa para redução da pressão intraocular (no período de pico) entre as três formulações de brimonidina.

PURPOSE: To compare the hypotensive effect in normal eyes of three formulations with different concentrations of brimonidine tartrate: 0.2%; 0.15% and 0.1%. METHODS: Prospective, randomized, double-blind study included 60 volunteers, who underwent initial ophthalmologic examination and measurement of intraocular pressure (IOP). Individuals were divided into three groups: (1) brimonidine tartrate 0.15%, (2) brimonidine tartrate 0.2% and (3) brimonidine tartrate 0.1% and randomly received one drop each of drops in each eye. The IOP was measured after 30 minutes, 1 hour and 2 hours. RESULTS: We found that all concentrations of brimonidine tartrate significantly reduced intraocular pressure during the study period, with p<0.05. When analyzing the percentage difference of the hypotensive effect of each group, we found no significant difference between the studied groups: (1) -13.50%, (2) -11.50%, (3) -11.90% after 30 minutes (p=0.650); (1) -24.30%, (2) -18.60%, (3) -18.30% after 1 hour (p=0.324); (1) -29.14%, (2) -21.20%, (3) -25.60% after 2 hours (p=0.068). CONCLUSION: There is no statistically significant difference in intraocular pressure reduction (peak period) between the three formulations of brimonidine.

The efficacy of topical administration of brimonidine to reduce ischaemia in the very early stage of diabetic retinopathy in good controlled type-2 diabetes mellitus.

It is now proved that diabetic micro-angiopathy is caused by ischaemia at the capillary bed of retina due to reduced capillary blood flow in long standing type-2 diabetes mellitus. Deranged metabolic process due to chronic hypoxia at the tissue level produces visual and vascular dysfunction. Brimonidine tartrate, an alpha-2 agonist which is commonly used in glaucoma to protect retinal ganglion cells from pressure related ischaemia induced cell apoptosis, is administered in very early stage of non-proliferative diabetic retinopathy to reduce ischaemia at the capillary bed of retina. Improved visual acuity and decreased micro-aneurysm formation, which indicate elimination of ischaemic stimulus at the tissue level, are seen in long standing type-2 diabetes mellitus.

Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression

1. Experiments using localized microinfusions of specific agonists and antagonists of neurotransmitter receptors have shown that the amygdala, hippocampus, medial septum and entorhinal cortex are involved in memory consolidation, storage and expression. The data are consistent with observations derived from lesion studies suggesting a role for these structures in memory processes, but permit many additional conclusions concerning the mechanisms involved and their timing. 2. Memories are initially processed by glutamatergic N-methyl-D-aspartate (NMDA) receptors in amygdala, hippocampus and medial septum, which are sensitive to amino-phosphono valerate (AP5). Memory of inhibitory avoidance is processed by the three structures; memory of habituation to a novel environment is processed only by the hippocampus. At the time of consolidation, immediately after training, gamma-aminobutyrate type A (GABA-A) receptors, modulated by endogenous benzodiazepines, play an inhibitory role, and cholinergic muscarinic and beta-noradrenergic transmission play a modulatory role. 3. From 90 to 180 min after training, memories are blocked by cyano-nitro-quinoxalinedione (CNQX) given into the amygdala, septum and hippocampus. CNQX blocks non-NMDA glutamatergic receptors. Also between 90 and 180 min after training, memory of the habituation and inhibitory avoidance tasks is blocked by the infusion of AP5 or of the GABA-A agonist, muscimol, into the entorhinal cortex. This late post-training intervention of the entorhinal cortex is essential for the integration of successively acquired memories, and occurs in response to the simultaneous activation of CNQX-sensitive synapses in amygdala and hippocampus. 4. The expression of memory is blocked by the infusion of CNQX, at the time of testing, into the amygdala and hippocampus (inhibitory avoidance), into the hippocampus but not the amygdala (habituation), or into the entorhinal cortex (for the two tasks). Since consolidation is blocked by AP5 infused into these structures (see above), the data agree with the hypothesis that memories are mediated by (or actually consist of) long-term potentiation (LTP) in these areas of the brain. LTP induction is blocked by AP5 and LTP expression is blocked by CNQX. It is possible that, at the time of memory expression, the entorhinal cortex is an output of the amygdala and hippocampus