Search PubMed⌕ Search

Biomedical subjects

R Spector

Publications and source records attributed to R Spector.

At least 145 records · Page 8Linked to original sources
PubMed1980

Diphenhydramine in Orientals and Caucasians.

The kinetics and psychomotor effects of diphenhydramine were investigated in Orientals and Caucasians. Each of 5 Oriental and 5 Caucasian young adults received on 1 of 3 occasions diphenhydramine 50 mg/70 kg body weight either intravenously or orally, or placebo. Plasma levels of diphenhydramine were measured hourly for 8 hr at each session. Tests of subjective sedation and psychomotor performance were performed at hourly intervals. The results showed that after both intravenous and oral diphenhydramine, at all times Orientals had plasma levels approximately half those of Caucasians. With the assumption of linear kinetics and a 1-compartment open model, analysis of the data showed that the volume of distribution (VD) and plasma clearance (Cl) but not plasma half-life (t 1/2) were higher in Orientals than Caucasians: [VD = 480 +/- 24 (SEM) and 292 +/- 36 1/70 kg; Cl = 79 +/- 7 and 51 +/- 7 1/70 kg/hr; t 1/2 = 4.1 +/- 0.4 and 4.3 +/- 0.4 hr]. Unbound diphenhydramine in fresh plasma was higher in Orientals than Caucasians [24.0 +/- 1.9% (SEM) and 14.8 +/- 1.5%] and probably explains the increased VD in Orientals. Orientals had significantly less sedation and deterioration in psychomotor performance.

Adult↗
PubMed1980

Transport of lignocaine by rabbit choroid plexus in vitro.

1. Lignocaine readily passes from blood into cerebrospinal fluid. The isolated rabbit choroid plexus, a locus of the blood-cerebrospinal fluid barrier, accumulated [14C]lignocaine by two processess: an active, saturable transport process and a non-saturable process. 2. The accumulation of [14C]lignocaine by choroid plexus was not due to non-specific binding or metabolism of lignocaine within or on the choriod plexus. 3. These results suggest that the choroid plexus may transport lignocaine between blood and cerebrospinal fluid in vivo by a specific carrier-mediated process.

Animals↗
PubMed1980

Methionine recycling in brain: a role for folates and vitamin B-12.

The recycling of methionine via homocysteine was measured in vivo in brain. After constant intravenous infusions (5 h) of both [3H-methyl]methionine and [35S]methionine into rats, the ratios of [3H-methyl]methionine to [35S]methionine in liver, brain, and plasma were determined. Similar experiments were performed in rabbits, except that the [3H-methyl]- and [35S]methionine were injected intraventricularly. If the methyl group of methionine was removed with the formation of homocysteine and then replaced by another (unlabeled) methyl group, the specific activity of the [3H-methyl]methionine would decrease more than that of [35S]methionine; i.e., the ratio of [3H-methyl]- to [35S]methionine in the tissue would decline. The results showed that the ratios of [3H-methyl]- to [35S]methionine in liver and brain were less than the same ratio in plasma in the rats. The comparable ratios in the brain and CSF of rabbits were less than the ratio in the injectate. Since brain contains only one enzyme capable of remethylating homocysteine to methionine, the vitamin B-12-dependent methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13), our results for methionine recycling via homocysteine in brain strongly support the activity of this enzyme in brain in vivo.

Animals↗
PubMed1980

Thymidine transport in the central nervous system.

The mechanisms by which thymidine enters and leaves brain, choroid plexus, and CSF were investigated by injecting [3H]thymidine intravenously and intraventricularly. [3H]thymidine, with and without unlabeled thymidine, was infused at a constant rate into conscious adult rabbits. At 150 min, [3H]thymidine readily entered CSF, choroid plexus, and brain. In brain, approximately 45% of the nonvolatile radioactivity was [3H]thymidine phosphates. The addition of 0.21 mmol/kg unlabeled thymidine to the infusion syringe decreased the phosphorylation of [3H]thymidine in brain by approximately 85%; the addition of 2.1 mmol/kg of unlabeled thymidine to the infusion syringe decreased the relative entry of [3H]thymidine into CSF and brain by 40 and 78%, respectively. Two h after intraventricular injection of [3H]thymidine, [3H]thymidine was rapidly cleared from CSF, in part, to brain, where approximately 40% of the [3H]thymidine was converted to [3H]thymidine phosphates. The intraventricular injection of unlabeled thymidine (21 mumol) with the [3H]thymidine abolished the phosphorylation of [3H]thymidine in brain and significantly decreased the clearance of [3H]thymidine from the CSF. Rabbit brain slices accumulated [3H]thymidine by an energy-dependent, saturable high-affinity system that depended, in part, on intracellular phosphorylation of the [3H]thymidine. These results were interpreted as showing that the entry of thymidine from blood into CSF and presumably the extracellular space of brain and then into brain cells involves one or more saturable transport and/or metabolic steps.

Animals↗
PubMed1980

Development and regional distribution of methionine synthetase in rabbit brain.

The development and regional distribution of methionine synthetase (EC 2.1.1.13) in rabbit brain was determined. In adult rabbits, the specific activity (units per milligram protein) of methionine synthetase in cortex, cerebellum, brain stem, and corpus striatum was comparable to the specific activity in whole brain (0.5 units/mg). In the first few weeks of life, the specific activity of methionine synthetase in whole rabbit brain declined from a value of 1.1 units/mg at 1 day of age to 0.5 units/mg at 6-10 weeks. Two-year-old rabbits had 0.6 units/mg in whole brain. These results show that: (a) methionine synthetase is distributed widely in mammalian brain and (b) methionine synthetase activity in brain declines relatively little with development.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1980

Riboflavin homeostasis in the central nervous system.

The mechanisms by which riboflavin, which is not synthesized in mammals, enters and leaves brain, CSF, and choroid plexus were investigated by injecting [14C]riboflavin intravenously or intraventricularly. Tracer amounts of [14C]riboflavin with or without FMN were infused intravenously at a constant rate into normal, starved, or probenecid-pretreated rabbits. AT 3 h, [14C]riboflavin readily entered choroid plexus and brain, and, to a much lesser extent, CSF. Over 85% of the [14C]riboflavin in brain and choroid plexus was present as [14C]FMN and [14C]FAD. The addition of 0.2 mmol/kg FMN to the infusate markedly depressed the relative entry of [14C]riboflavin into brain, choroid plexus, and, less so, CSF, whereas starvation increased the relative entry of [14C]riboflavin into brain and choroid plexus. After intraventricular injection (2 h), most of the [14C]riboflavin was extremely rapidly cleared from CSF into blood. Some of the [14C]riboflavin entered brain, where over 85% of the 14C was present as [14C]FMN plus [14C]FAD. The addition of 1.23 mumol FAD (which was rapidly hydrolyzed to riboflavin) to the injectate decreased the clearance of [14C]riboflavin from CSF and the phosphorylation of [14C]riboflavin in brain. Probenecid in the injectate also decreased the clearance of [14C]riboflavin from CSF. These results show that the control of entry and exit of riboflavin is the mechanism, at least in part, by which total riboflavin levels in brain cells and CSF are regulated. Penetration of riboflavin through the blood-brain barrier, saturable efflux of riboflavin from CSF, and saturable entry of riboflavin into brain cells are three distinct parts of the homeostatic system for total riboflavin in the central nervous system.

Animals↗
PubMed1980

Riboflavin transport in the central nervous system. Characterization and effects of drugs.

The relationship of riboflavin transport to the transport of other substances including drugs in rabbit choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, and brain cells were studied in vivo and in vitro. In vitro, the ability of rabbit choroid plexus to transport riboflavin from the medium (cerebrospinal fluid surface) through the choroid plexus epithelial cells into the extracellular and vascular spaces of the choroid plexus was documented using fluorescence microscopy. These studies provided further evidence that riboflavin is transported from cerebrospinal fluid to blood via the choroid plexus. The transport of [14C]riboflavin by the isolated choroid plexus was inhibited by thiol agents, ouabain, theophylline, various flavins (lumiflavin and lumichrome > sugar containing flavins), and cyclic organic acids including penicillin and fluorescein. Riboflavin inhibited [14C]penicillin transport competitively and the inhibition constant (K1) for riboflavin equaled the concentration of riboflavin at which the saturable transport system for riboflavin is 50% saturated (KT). These and other data suggest that riboflavin, penicillin, and possibly fluorescein are transported by the same transport system in choroid plexus. In vivo, the intra-ventricular injection or riboflavin and [14C]penicillin inhibited [14C]penicillin transport from cerebrospinal fluid. In vitro, various flavins (riboflavin > other sugar-containing flavins > lumiflavin > lumichrome) inhibited [14C]riboflavin accumulation by brain slices. These studies support the notions that: (a) riboflavin accumulation by choroid plexus (active transport) is quite different from that in brain cells (facilitated diffusion and intracellular trapping), and (b) therapeutically important cyclic organic acids (e.g., penicillin) are transported fom cerebrospinal fluid by the riboflavin transport system in choroid plexus.

Animals↗
PubMed1980

Effect of sodium chloride on gentamicin accumulation by Escherichia coli: correlation with bacterial growth and viability.

The kinetics of gentamicin accumulation by a sensitive strain of Escherichia coli were investigated at gentamicin concentrations from 0.02 to 200 microgram/ml. Accumulation with time shows two energy-dependent phases and is saturable. Sodium chloride delays the onset of the second more rapid energy-dependent phase and decreases the magnitude of gentamicin accumulation for incubations up to 60 minutes at all gentamicin concentrations tested. Simultaneous determinations of accumulation, cell viability, and growth inhibition indicate that antimicrobial activity is correlated with the magnitude of gentamicin accumulation. These observations suggest that altered bacterial accumulation of gentamicin explains the effect of sodium chloride on the antimicrobial activity of gentamicin.

Escherichia coli↗
PubMed1979

Active transport of riboflavin by the isolated choroid plexus in vitro.

In vitro, the transport of [14C]riboflavin into and from the isolated choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, was studied. With concentrations of [14C]riboflavin of 0.7 microM (or greater) in the incubation medium, the choroid plexus accumulated [14C]riboflavin against a large concentration gradient by a process that did not depend on binding or intracellular metabolism of the [14C]riboflavin. The [14C]riboflavin accumulation process in isolated choroid plexus could be described by Michaelis-Menten transport kinetics (kt = 78 microM and Ymax = 1.65 mmol kg-1 (15 min)-1) and was inhibited by other flavins and probenecid but not by ribose, weak bases, or other B vitamins. The accumulation process was markedly depressed by iodoacetate and low temperatures. With a concentration of 0.08 microM [14C]riboflavin in the incubation medium, 28% of the [14C]riboflavin within the choroid plexus was converted to [14C]FAD or [14C]FMN intracellularly. Unlike the active transport of [14C]riboflavin into choroid plexus, accumulated [14C]riboflavin departed choroid plexus by a process independent of intracellular concentration or temperature. The efflux of [14C]riboflavin from choroid plexus could be described by first oder kinetics with a rate constant of -0.08 min-1.

Animals↗
PubMed1979

Is idiopathic dementia a regional vitamin deficiency state?

We hypothesize that some cases of idiopathic dementia are due to a gradual undernourishment of the brain with water-soluble vitamins. This occurs because the choroid plexus and possibly other transport loci in the central nervous system become unable to transport water-soluble vitamins from blood into the central nervous system in adequate amounts. If this testable hypothesis is correct, direct injections of vitamins into the ventricular cerebrospinal fluid should ameliorate the development of dementia.

Ascorbic Acid↗