To determine whether plasma lactate can be a significant fuel for human brain energy metabolism, infusions of [3-(13)C]lactate and (1)H-(13)C polarization transfer spectroscopy were used to detect the entry and utilization of lactate. During the 2 h infusion study, (13)C incorporation in the amino acid pools of glutamate and glutamine were measured with a 5 min time resolution. With a plasma co...

Species differences occur in the brain concentrations of drugs, but the reasons for these differences are not yet apparent. This study was designed to compare brain uptake of three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain concentrations and brain-to-plasma ratios were compared; [(11)C]verapamil in rats, guinea pigs, and monkeys; [(11...

The comparative accumulation of C(4)-C(15) perfluorinated sulfonates (PFSAs) and carboxylates (PFCAs), and several precursors (e.g., perfluorooctane sulfonamide, N-methyl-FOSA, and fluorotelomer unsaturated acids and alcohols) was examined in tissues (liver, brain, muscle, and adipose), plasma/red blood cells (RBCs) and whole egg clutches (yolk and albumen) of female herring gulls collected in ...

It may be inferred from the presence of P-glycoprotein (Pgp) in brain capillaries that this drug efflux pump is a factor in limiting the penetration of certain agents into brain tumors. However, by contrast with normal brain capillaries which constitute the blood-brain barrier, brain tumor capillaries are compromised or "leaky," and the extent to which Pgp expression in brain tumor neovasculatu...

-Concentrations of the hypoxic cell radiosensitizer misonidazole (MIS) and its 0 -demethylated metabolite Ro 05 -9963 were determined in plasma (or blood), brain and tumour after injection of I g/kg MIS i.p. to control mice or mice pretreated with 4-6 daily injections of phenobarbitone or phenytoin. Analysis was by highperformance liquid chromatography (HPLC). Phenobarbitone and phenytoin did n...

AIMS In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS Patients with traumat...

BACKGROUND We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats. METHODS Lidocaine (0.5 mg x kg x min), bupivacaine (0.1 mg x kg x min), or levobupivacaine (0.1 mg x kg x min) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dia...

thrombotic thrombocytopenic purpura is the result of multiple thrombus disseminated in small arterioles throughout the body. principle damage is in the endothelium of small vessels and capillaries. from 1982 to 1999, 28 patients (16 female and 12 male) have been treated for ttp. the outcome was evaluated for risk factors and prognosis. these patients were 18 to 69 years old. all had neurologica...

A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emiss...

The study objectives were 1) to test the hypothesis that the lack of P-glycoprotein (P-gp) and the inhibition of breast cancer resistance protein (Bcrp) at the blood-brain barrier after cassette dosing of potent P-gp and Bcrp inhibitors were due to low plasma concentrations of those inhibitors and 2) to examine the effects of P-gp on the unbound brain (Cu,brain) and cerebrospinal fluid (CSF) co...