PubMed Health⌕ Search

Biomedical subjects

R Spector

Publications and source records attributed to R Spector.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of leukotriene C4 on the cerebral microvasculature.

Leukotriene C4, which is synthesized during cerebral ischemia, may contribute to disruption of the blood-brain barrier. The purpose of this study was to determine whether leukotriene C4 constricts cerebral arterioles and disrupts the blood-brain barrier. We used intravital fluorescent microscopy in hamsters and compared responses of vessels in the cerebrum with vessels in the cheek pouch. Increases in permeability of the cheek pouch and disruption of the blood-brain barrier were quantitated after superfusion with leukotriene C4 (0.3, 3.0, and 30 nM) by the formation of microvascular leaky sites. Changes in diameter of arterioles in the cheek pouch and cerebrum also were examined. In the cheek pouch, leukotriene C4 produced a dose-related decrease in diameter of arterioles (maximum = 40 +/- 8%; mean +/- SE) and an increase in microvascular permeability (maximum = 16 +/- 2 leaky sites). In contrast, in the cerebrum, leukotriene C4 produced only modest constriction of arterioles (maximum = 12 +/- 5%) and minimal disruption of the blood-brain barrier (maximum = 2 +/- 1 leaky sites). Thus the findings indicate that leukotriene C4, in contrast to its potent vasoconstrictor effects and increase in permeability in the hamster cheek pouch, produces only modest cerebral vasoconstriction and minimal disruption of the blood-brain barrier.

Animals↗
PubMed1986

Pantothenic acid transport and metabolism in the central nervous system.

The mechanisms by which pantothenic acid (PA) enters and leaves brain, choroid plexus, and cerebrospinal fluid (CSF) were investigated by injecting [3H]PA either intravenously or intraventricularly into adult rabbits. [3H]PA, either alone or together with unlabeled PA, was infused at a constant rate into conscious rabbits. At 180 min, [3H]PA readily entered CSF, choroid plexus, and brain. In brain, CSF, and plasma, greater than 90% of the 3H was associated with [3H]PA. The addition of 200 mumol/kg PA to the infusion syringe decreased the penetration of [3H]PA into brain and CSF by approximately 70%. Two hours after the intraventricular injection of [3H]PA, [3H]PA was rapidly cleared from the CSF by a probenecid-sensitive mechanism. No metabolism of the [3H]PA occurred in brain. However, 18 h after the intraventricular injection of 37 microCi (34 nmol) of [3H]PA, approximately 40% of the 3H remaining in forebrain was converted to [3H]CoA. These results show that PA enters and leaves CSF and brain by saturable transport systems. However, [3H]PA is very slowly converted to [3H]CoA in brain in vivo.

Animals↗
PubMed1986

Phenobarbital improves survival in theophylline-intoxicated rabbits.

As in humans, theophylline intoxication in rabbits causes seizures and death. We studied whether the administration of phenobarbital or phenytoin following a toxic dose of theophylline would improve survival in rabbits. New Zealand white rabbits were infused intravenously with theophylline, 115 mg/kg over 50 minutes. Upon completion of the infusion, rabbits were randomized to receive either saline (control) (N = 60) or saline containing phenobarbital 20 mg/kg (N = 60), or phenytoin 12 mg/kg (N = 30), infused over 30 minutes. The number (and percentage) of rabbits surviving 24 hours in each group was: control 12 (20%), phenobarbital 30 (50%), and phenytoin 7 (23%) [X2; p less than 0.005; two-tailed]. In all fatal cases, death was preceded by a seizure; rabbits that survived did not seize. These results show that phenobarbital administered intravenously to theophylline-intoxicated rabbits prevented seizures and improved survival whereas phenytoin administration had no significant effect.

Animals↗
PubMed1986

The nerve cell.

Explore the source record for details and available documents.

Animals↗
PubMed1986

Transport and metabolism of vitamins.

Although the biochemical roles of most vitamins in the body are reasonably well understood, our knowledge of how the body transports and metabolizes the vitamins is incomplete. This paper summarizes the information available on riboflavin, vitamin B-6, biotin, vitamin D, vitamin C, and pantothenic acid. As might be expected on the basis of the diverse chemistry and biology of these substrates, the body has quite unique mechanisms for handling each of them.

Animals↗
PubMed1986

Ceftriaxone pharmacokinetics in the central nervous system.

The transport and metabolism of ceftriaxone was studied in vitro in the isolated choroid plexus and in vivo in New Zealand White rabbits. In vitro, [14C]ceftriaxone was accumulated by a saturable, probenecid-sensitive system in choroid plexus, although much less readily than [14C]penicillin G. Ceftriaxone was also a much less potent inhibitor of [14C]penicillin G accumulation by the isolated choroid plexus than penicillin G itself (IC50 = 1.6 vs. 0.07 mM, respectively). In vivo, 2 hr after intraventricular injection, [14C]ceftriaxone was not metabolized or cleared from the cerebrospinal fluid more rapidly than [3H]mannitol, a molecule transported in the central nervous system by simple diffusion. These in vitro and in vivo results show that ceftriaxone, unlike penicillin G, has minimal affinity for the choroid plexus active transport system that transfers most penicillins and cephalosporins from cerebrospinal fluid to blood.

Animals↗
PubMed1986

Expanded role of charcoal therapy in the poisoned and overdosed patient.

Activated charcoal is widely used as an adsorbent for the management of patients with drug overdoses and poisonings. Activated charcoal can be used orally to prevent drug and poison absorption in cases of overdose and poisoning. Multiple oral doses of charcoal increase the elimination of several, but not all, drugs and poisons. The effectiveness of multiple oral doses of charcoal in accelerating drug clearance is dependent primarily on the endogenous clearance of the drug or poison and its volume of distribution. Multiple doses of charcoal are used to shorten the period of supportive care in certain patients or to more rapidly remove drugs or poisons that may cause tissue damage, eg, theophylline. Charcoal is a safe, effective, and inexpensive alternative to more invasive treatments for some cases of drug overdose and poisoning.

Administration, Oral↗
PubMed1986

An approach to the management of the poisoned patient.

Our systematic approach to the evaluation and treatment of the acutely poisoned patient involves establishing an accurate diagnosis and prognosis that often may be based on quantitation of the blood concentration of the toxic substance. The major feature of this approach is the proper selection of treatment(s) for the poisoned patient, ie, decontamination and supportive care and, in some cases, antidotal therapy and/or active removal of the toxic substance. Invasive, expensive methods of active removal (eg, hemodialysis or hemoperfusion) are generally recommended only if specific criteria are satisfied. Noninvasive, inexpensive methods of active removal (eg, manipulation of urinary pH or the oral administration of multiple doses of activated charcoal) may have significant utility in the treatment of poisoned patients not requiring invasive methods. This systematic approach to the poisoned patient should lead to an effective use of treatment modalities with minimal risks and optimal clinical results.

Acute Disease↗
PubMed1985

The effect of dietary protein on the clearance of allopurinol and oxypurinol.

A decrease in dietary protein is known to depress renal plasma flow and creatinine clearance. Using a randomized crossover design, we investigated the pharmacokinetics of allopurinol and its principal metabolite, oxypurinol, after oral administration of 600 mg of allopurinol in six normal subjects receiving a high-protein (268 g per day) or low-protein (19 g per day) diet. For allopurinol, the area under the curve of plasma concentration versus time increased by a factor of 1.45 (P less than 0.02), the renal clearance decreased by 28 per cent (P less than 0.02), and the ratio of the clearance of allopurinol to that of creatinine (fractional excretion) was unchanged between the low-protein and high-protein diets. For oxypurinol, the area under the curve increased nearly three-fold (P less than 0.02), the renal clearance decreased by 64 per cent (P less than 0.02), the fractional excretion decreased by 49 per cent (P less than 0.02), and the plasma oxypurinol half-life increased nearly threefold from 17.3 +/- 1.5 (mean +/- S.E.M.) to 49.9 +/- 2.9 hours (P less than 0.02) during the low-protein diet, as compared with the high-protein diet. We conclude that with the low-protein diet, the absorption, metabolism, and excretion of allopurinol were minimally altered but the total-body clearance of oxypurinol was greatly reduced because of a large increase in the net renal tubular reabsorption of oxypurinol.

Adult↗
PubMed1985

Leukotriene C4 transport by the choroid plexus in vitro.

Nanomolar concentrations of peptidoleukotrienes evoke sustained cerebral edema and arterial constriction. Peptidoleukotrienes are thus considered to play an important role in eliciting cerebral edema after cerebral ischemia and vasospasm after subarachnoid hemorrhage. It was hypothesized that the choroid plexus, the locus of the blood-cerebrospinal fluid barrier, might minimize the vasoactivity of locally generated or systemically derived leukotrienes by transporting leukotrienes from cerebrospinal fluid into the blood. Consistent with this hypothesis, leukotriene C4 in vitro was transported into and released from isolated rabbit choroid plexus by a system that was specific, energy-dependent, probenecid-sensitive, and depressed by cold temperatures. The accumulation of leukotriene C4 in the choroid plexus was not dependent on tissue binding or metabolism of leukotriene C4.

Animals↗
PubMed1985

Search for DNA alterations in Alzheimer's disease.

The DNA of brain cortex obtained from autopsy specimens of eight patients with Alzheimer's disease and eight controls was examined for content of normal and abnormal bases. DNA, purified by hydroxyapatite chromatography, was hydrolyzed under mild conditions and the deoxynucleosides were measured by high performance liquid chromatography (HPLC). No differences in the mole percentages of deoxynucleosides in DNA were detected in patients with Alzheimer's disease compared to controls, nor were abnormal deoxynucleosides found. Restriction-nuclease digests examined by agarose gel electrophoresis also showed no changes. Thus, diffuse and persistent damage to the DNA in brain in Alzheimer's disease was not detected by these methods.

Aged↗
PubMed1985

Lack of effect of oral activated charcoal on imipramine clearance.

The effect of oral activated charcoal on the pharmacokinetics of intravenous imipramine was studied in a randomized, crossover trial. Four normal men received intravenous imipramine (12.5 mg/70 kg) on two separate occasions, followed by either water or water plus high-surface-area activated charcoal (180 gm) in divided doses over 24 hours. Serum imipramine concentrations were measured from 0 to 24 hours after the imipramine infusion. There was no difference in the mean (+/- SE) t1/2 (9.0 +/- 0.8 vs. 10.9 +/- 1.6 hours), apparent volume of distribution (11.2 +/- 2.1 vs. 12.4 +/- 2.1 L/kg), or systemic clearance (992.2 +/- 138.3 vs. 930.3 +/- 101.9 ml/min/70 kg) of imipramine after dosing without and with oral activated charcoal, respectively (P greater than 0.05; paired t test). These results suggest that multiple oral doses of activated charcoal do not increase the clearance of imipramine in man.

Absorption↗