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Many therapeutic drugs are excluded from entering the brain, due to their lack of transport through the blood-brain barrier (BBB). To overcome this problem, we have developed a novel method in which short, naturally derived peptides (16-18 amino acids) cross the cellular membranes of the BBB with high efficiency and without compromising its integrity. The(More)
Transport of a polyamine (PA), spermidine (SPMD) into rat brain at various early postischemic periods was studied. Rats underwent 20 min of four-vessel occlusion (4VO) followed by 5, 10, 30 and 60 min of recirculation (RC) periods with natural brain temperature. 3H-aminoisobutyricacid (AIB) and 14C-SPMD were utilised to search dual functions of the(More)
Studies of drug distribution to brain should be controlled for the experimental method used. Numerous methods have been employed to ascertain brain distribution and many of these approaches use anesthetic agents. The in situ rat brain perfusion method is one of the most sensitive and widely used methods for evaluating brain distribution profiles. There has(More)
Doxorubicin delivery to the brain is often restricted because of the poor transport of this therapeutic molecule through the blood-brain barrier (BBB). To overcome this problem, we have recently developed a technology, Pep:trans, based on short natural-derived peptides that are able to cross efficiently the BBB without compromising its integrity. In this(More)
Exposure of immature rats to lead acetate results in hemorrhagic encephalopathy of variable evolution. As the maintenance of adequate protection against peroxides may be critical in this condition, the activities of selenium-glutathione peroxidase and catalase in cerebrum and cerebellum of suckling rats poisoned with lead acetate were studied from day six(More)
Brain capillaries isolated from 2-month-old male and female Sprague-Dawley rats were used to study the transport of neutral amino acids. The uptake of alanine, leucine, and alpha-methylaminoisobutyric acid (MeAIB) was a linear function of time for the first minute of incubation. Based on these observations, an incubation time of 1 min was used to measure(More)
Classically, drug penetration through the blood-brain barrier depends on the lipid solubility of the substance, except for some highly lipophilic drugs, like colchicine and vinblastine, both substrates of P-glycoprotein, a drug efflux pump present at the luminal surface of the brain capillary endothelial cells. Colchicine and vinblastine uptake into the(More)
Transport of L-glutamate from blood to brain in equithesin-anesthetized rats was examined using in situ brain perfusion combined with multiple-time/graphical analysis. In situ perfusion allowed precise control of the composition of the perfusate, which was necessary for a detailed investigation of glutamate transport, while multiple time/graphical analysis(More)
Transport of taurine has been demonstrated in capillary preparations from adult rat brains using [3H]taurine. Taurine transport is mediated by a saturable high-affinity system which is entirely dependent on sodium ions. The apparent maximal influx (Vmax) and half-saturation concentration (Km) corresponded to 1.06.10(-4) mumol/min per mg protein and 27.5(More)
Taurine transport into six brain regions of equithesin-anesthetized rats was studied by the in situ brain perfusion technique. This technique gives both accurate measurements of cerebrovascular amino acid transport and allows complete control of the perfusate amino acid composition. Final wash procedure showed that taurine efflux occurred rapidly from(More)