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Biomedical subjects

R Spector

Publications and source records attributed to R Spector.

At least 109 records · Page 6Linked to original sources
PubMed1982

Diphenhydramine: kinetics and psychomotor effects in elderly women.

Kinetics and sedative and psychomotor effects of diphenhydramine were investigated in elderly Caucasian women (greater than 64 yr. old). In a double-blind trial, each of 12 healthy subjects received on one of three occasions 50 mg/70 kg IV or oral diphenhydramine HCl or oral placebo. Plasma levels of diphenhydramine were measured in six subjects and tests of sedation and psychomotor performance were performed hourly for 8 hr in all subjects. Kinetic analysis showed that the volume of distribution (295 +/- 50 [SEM] l/70 kg), clearance (42 +/- 5 l/70 kg/hr), and plasma t1/2 (4.9 +/- 0.7 hr) were of the same order as in young adults. As in young adults, there was minimal psychomotor impairment after oral and after intravenous diphenhydramine. In contrast to young adults, however, elderly women did not report significant sedation after diphenhydramine. These results suggest that diphenhydramine may not be an effective sedative/hypnotic in elderly women.

Administration, Oral↗
PubMed1982

Metabolism of deoxyuridine in rabbit brain.

The metabolism of [3H]deoxyuridine by rabbit brain was investigated in vitro and in vivo. In vitro, brain slices from various regions of brain and from all age groups accumulated [3H]deoxyuridine from artificial CSF. Within the slices, a portion of the accumulated [3H]deoxyuridine was metabolized to [3H]deoxyuridine phosphate, with subsequent conversion to [3H]thymidine phosphate, and ultimately [3H]DNA. The percentage of the [3H]deoxyuridine phosphorylated and subsequently converted into [3H]DNA was highest at birth and declined to adult levels in 3-month-old rabbits. Thymidine, when added to the incubation medium with the [3H]deoxyuridine, was approximately 10 times as potent as unlabeled deoxyuridine in inhibiting the intracellular phosphorylation and conversion of [3H]deoxyuridine to [3H]thymidine phosphate in brain slices. In vivo, 2.5 h after intraventricular injection of [3H]deoxyuridine, over 90% of the [3H]deoxyuridine was cleared from the central nervous system at all ages. However, in both newborn and 3-month-old rabbits, approximately 40 and 12%, respectively, of the 3H remaining in brain was phosphorylated and converted to [3H]thymidine phosphates; and 11 and 4%, respectively, of the 3H remaining in brain was converted to [3H]DNA. These results show that both immature and mature rabbit brain is able to incorporate deoxyuridine into DNA. Thus, all the enzymes involved in this conversion, including thymidylate synthetase (EC 2.1.1.45), are present and active in brain throughout life.

Aging↗
PubMed1982

Localization and mechanism of thymidine transport in the central nervous system.

The localization and mechanism of thymidine and deoxyuridine transport in the central nervous system were studied in vivo and in vitro. Previous studies have shown that thymidine enters brain from blood in part via the CSF. In vitro, isolated adult bovine cerebral microvessels, which readily concentrated and phosphorylated deoxyglucose, were unable to concentrate thymidine and deoxyuridine. In vivo, [3H]thymidine (0.2 microM) and [3H]deoxyuridine (0.4 microM) were not extracted more readily than [14C]sucrose in a single pass through the cerebral circulation of rats. In vivo, [3H]thymidine retention in CSF and brain after entry from blood was increased when the efflux of [3H]thymidine from CSF and the phosphorylation of [3H]thymidine in brain were depressed by the intraventricular injection of unlabeled thymidine. These studies and previous work suggest that the transfer of thymidine (and deoxyuridine) through the blood-brain barrier in either direction must be extremely low. The present studies are consistent with the postulate that thymidine is transported by an active transport system in the choroid plexus that transfers thymidine from blood into the CSF; from the CSF, the thymidine enters brain cells and is phosphorylated.

Animals↗
PubMed1982

Identification, development, and regional distribution of thymidylate synthetase in adult rabbit brain.

The development and regional distribution of thymidylate synthetase (TS) (EC 2.1.1.45) in rabbit brain were determined. After optimization of the assay for brain, TS activity in brain was measured by a nonspecific (3H2O release) and specific method. The specific method involved the conversion of [6-3H]deoxyuridine monophosphate (dUMP) to [3H]thymidine phosphate and the subsequent identification of [3H]thymidine.l The specific activity of the enzyme in whole brain of newborn rabbits declined from 10.35 +/- 1.17 units/mg protein to 0.71 +/- 0.09 units/mg protein at 10-12 weeks of age. Two=year-old rabbits had 0.81 +/- 0.04 units/mg protein. The decline in specific activity with age was not due to an inhibitor of TS activity or a change in the Km for dUMP. The Km for dUMP of the unpurified enzyme in the brains of both 19-day-old and young adult rabbits was 0.8 microM. In young adult rabbits (3 months) the specific activity of TS was similar in the various regions of the brain tested except for the cerebellum, which had 40% higher specific activity than the whole brain. The results show that TS is widely distributed in adult rabbit brain, and, although the activity declines with age, it stabilizes at adult levels at 3 months of age.

Aging↗
PubMed1982

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

In vitro, the transport of [14C]nicotine into the isolated choroid plexus, the anatomical locus of the blood--CSF barrier, was studied. The isolated rabbit choroid plexus accumulated [14C]nicotine by two processes: an active saturable transport process and a nonsaturable process. The [14C]nicotine accumulation process by choroid plexus was not due to binding or intracellular metabolism of the [14C]nicotine. The [14C]nicotine accumulation process in isolated choroid plexus was inhibited by weak bases, including tolazoline and lidocaine, but not by the weak acid probenecid. The accumulation process was decreased 60% by iodoacetate and dinitrophenol and by low temperatures. These results are consistent with previous autoradiographic evidence showing the choroid plexus concentrated [14C]nicotine in vivo, and suggest that the choroid plexus may transfer nicotine between blood and CSF in vivo.

Animals↗
PubMed1982

Serious adverse reactions associated with sulindac.

Sulindac is a nonsteroidal anti-inflammatory agent that has been associated with serious adverse reactions. We saw four patients with reactions associated with sulindac. Our patients, one of whom died, had high temperatures and involvement of one or more organs, including the skin, liver, CNS, lymph nodes, bone marrow, and lungs. Eight similar previously reported cases also are summarized. In view of these cases of sulindac-induced toxicity, six of which were proved unequivocally by drug rechallenge, we suggest that physicians be cautious in prescribing this agent.

Adult↗
PubMed1982

Riboflavin transport by rabbit kidney slices: characterization and relation to cyclic organic acid transport.

The transport of riboflavin and the relationship of riboflavin transport to the transport of the cyclic organic acids, aminohippurate and penicillin, were investigated in small renal slices in vitro. Riboflavin was accumulated by rabbit renal slices by a transport system that was inhibited by sugar-containing and sugarless flavins, cyclic organic acids including aminohippurate and penicillin, dinitrophenol and cold temperatures, but not by D-ribose or the weak base tolazoline. The transport of riboflavin into renal slices was not solely due to intracellular binding or metabolism of the riboflavin. Aminohippurate, penicillin and riboflavin inhibited the active accumulation of [14C] aminohippurate and [14C]penicillin by kidney slices. These studies support the notions that: 1) riboflavin is accumulated in kidney cortex slices by an energy-dependent saturable transport system; 2) riboflavin accumulation by kidney slices is inhibited by cyclic organic acids and sulfhydryl reagents, but not weak bases; and 3) riboflavin is a competitive inhibitor of aminohippurate as well as an inhibitor of penicillin G accumulation by kidney slices.

Aminohippuric Acids↗
PubMed1982

Pharmacokinetics and metabolism of cytosine arabinoside in the central nervous system.

The pharmacokinetics and metabolism of [3H] cytosine arabinoside in the central nervous system were investigated. In vitro, the ability of rabbit brain slices and the isolated choroid plexus to accumulate [3H] cytosine arabinoside from artificial cerebrospinal fluid (CSF) containing 5 nM [3H] cytosine arabinoside was studied. Although in both tissues the uptake of [3H] cytosine arabinoside was saturable, neither brain slices nor the isolated choroid plexus achieved tissue/medium ratios greater than 1.0 in 30 min. After 15-min incubations iin artificial CSF containing 5 nM [3H] cytosine arabinoside, 8 +/- 2 (S.E.M.;N = 3)% of the 3H within the choroid plexuses was [3H] cytosine arabinoside phosphates; after comparable 30-min incubations, 4 +/- 1 (N = 4)% of the 3H within brain slices was [3H] cytosine arabinoside phosphates. In vivo, 2 hr after the i.c.v. injection into rabbits of [3H] cytosine arabinoside and 0, 2 ro 20 mumol of unlabeled cytosine arabinoside, it was shown that: 1) high concentrations of cytosine arabinoside in the CSF decreased the clearance of cytosine arabinoside from the CSF; 2) cytosine arabinoside was taken up and phosphorylated by brain cells in all regions tested; and 3) although the phosphorylation of [3H] cytosine arabinoside in brain cells was saturable, a portion of the [3H] cytosine arabinoside in brain was phosphorylated to [3H] cytosine arabinoside triphosphate even when the i.c.v. injectate contained 20 mumol of unlabeled cytosine arabinoside.

Animals↗
PubMed1982

Verapamil.

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Humans↗