PubMed Health⌕ Search

Biomedical subjects

R A Yokel

Publications and source records attributed to R A Yokel.

14 recordsLinked to original sources
PubMed1992

Antipyrine as a dialyzable reference to correct differences in efficiency among and within sampling devices during in vivo microdialysis.

Antipyrine was investigated as a dialyzable substance that could be used to quantitate relative differences in the efficiency of dialysis among multiple microdialysis probes and by a single probe over time. The contribution of effective membrane surface area to recovery variability was tested by the introduction of air into microdialysis probes. Reduction of effective membrane surface area reduced antipyrine recovery. Dialysates from probes implanted in the jugular vein, brain, and liver of rats receiving antipyrine demonstrated differences in antipyrine concentration among probes within the same rat. These results suggest dissimilar efficiencies of the probes to recover antipyrine, which should be uniformly distributed throughout body water. Dialysates from blood, brain, and liver probes in rats that received both antipyrine and tritiated water (3H2O) showed differences in antipyrine and 3H2O concentrations among probes. Variability of antipyrine and 3H2O concentrations over time within a probe were positively correlated, suggesting that the cause(s) of temporal variability affected both of these markers of body water. Correction of antipyrine tissue/blood ratios, using 3H2O blood/tissue ratios from the same sampling period, reduced the variability in antipyrine tissue/blood ratios, producing ratios closer to the expected value of 1. Differences in probe efficiency contributing to the variability of antipyrine and 3H2O recovery would also be expected to influence the recovery of other substances during microdialysis. The administration of antipyrine during microdialysis experiments is suggested to enable reduction of temporal and site-related differences in substance recovery that are due to differences in probe efficiency. Other methods are necessary to determine the actual extracellular concentration of dialyzed substances and the integrity of the blood-brain barrier.

Animals↗
PubMed1992

4-Trimethylammonium antipyrine: a quaternary ammonium nonradionuclide marker for blood-brain barrier integrity during in vivo microdialysis.

The well-controlled microdialysis (MD) study of substance permeation into brain extracellular fluid (ECF) and cerebrospinal fluid requires consideration of blood-brain barrier (BBB) integrity, which might be compromised by microdialysis probe implantation. Others have assessed BBB integrity with radionuclide markers. A nonradionuclide marker may be desirable in many studies. A charged antipyrine analogue may be useful to determine BBB integrity with concomitant antipyrine characterization of probe efficiency (Yokel et al., 1992, J Pharmacol Toxicol Methods 27:135-142), and may not require another analytical technique. We synthesized, validated, and evaluated 4-trimethylammonium antipyrine (4TMA-AP) as a BBB integrity marker. BBB permeation was determined by calculation of a BBB integrity percentage (Pi) from brain/blood concentrations. The PiS of Evan's blue, which does not permeate the intact BBB, and 4TMA-AP were not significantly different in rats without known BBB disruption, suggesting a lack of 4TMA-AP permeation through the intact BBB. When MD probes were slowly implanted into the frontal cortex, 4TMA-AP PiS were usually zero. Intracarotid oleic acid injection to open the BBB significantly increased 4TMA-AP PiS, suggesting that 4TMA-AP entered brain ECF when the BBB was compromised. Rapid probe implantation produced increased 4TMA-AP PiS, suggesting BBB disruption. The predicted appearance of 4TMA-AP in brain ECF suggests that it is a BBB integrity marker.

Animals↗
PubMed1992

Aluminum inhibits glutamate release from transverse rat hippocampal slices: role of G proteins, Ca channels and protein kinase C.

Aluminum (Al) has been shown to produce deficits in learning and memory. The present experiments tested the hypothesis that Al-induced inhibition of learning may be due to its effect on glutamate release secondary to changes in calcium channel function and/or intracellular events triggering glutamate release. Calcium-dependent potassium (K)-evoked [14C]-glutamate release from 400 microns transverse rat hippocampal slices was inhibited by Al in a concentration dependent manner (IC50 = 40 microM). Aluminum (30, 100 microM) noncompetitively inhibited Bay K 8644-evoked glutamate release. 4-Aminopyridine (30, 1000 microM) noncompetitively attenuated the Al inhibition of glutamate release, suggesting an Al-induced alteration of Ca channel function. Activation of the Gi protein by R(-)phenylisopropyladenosine (PIA; 1 microM) reduced K-evoked glutamate release 69%, whereas 300 microM Al produced an 84% reduction. These effects were prevented by the Gi protein inhibitor N-ethylmaleimide (NEM; 100 microM), suggesting an effect of Al on the Gi protein to inhibit glutamate release. Phorbol myristate acetate (0.16 microM)-induced glutamate release was inhibited by 300 microM Al and 80 microM polymyxin B, suggesting an Al modulation of protein kinase C (PKC)-evoked glutamate release. These results demonstrate an Al inhibition of glutamate release that may be mediated by multiple, but interconnected mechanisms (e.g., via interactions with Ca systems), providing multiple targets for an Al-induced alteration of neuronal function.

4-Aminopyridine↗
PubMed1979

Abuse and pulmonary complications of injecting pentazocine and tripelennamine tablets.

A current practice among drug abusers in certain Midwestern and Eastern cities is the intravenous injection of aqueous mixtures prepared from tablets of pentazocine and tripelennamine. Patients present with acute hypoxic episodes and symptoms suggesting physical dependence to pentazocine. Two cases are presented illustrating acute respiratory distress with hypoxia. Available evidence indicates that the respiratory syndrome is produced by talc from the injected tablets. Respiratory support and short-term oxygen therapy have been effective in managing this syndrome. Approaches to the treatment of pentazocine dependence and the role of the antihistamine in potentiating the narcotic activity are also discussed. Physicians, drug abuse counselors, and others should be aware of the abuse potential and pulmonary damage which can result from the intravenous use of this drug combination.

Adult↗
PubMed1979

Repeated naloxone administration for morphine overdose in a 1-month-old infant.

Repeated injections of naloxone by hydrochloride, a pure narcotic antagonist, were administered to a 3,320-gm 4-week-old boy for treatment of an accidental morphine overdose. The infant received frequent naloxone hydrochloride injections (0.2 mg per injection) during the first 12 hours of therapy to reverse morphine-induced apnea, hypothermia, and flaccidity. A cumulative dose of 2.73 mg of naloxone hydrochloride (0.822 mg/kg) was administered over 27 hours without apparent adverse effect or evidence of toxicity.

Humans↗
PubMed1978

Amphetamine- type reinforcement by dopaminergic agonists in the rat.

Intravenous self-administration of d-amphetamine (0.25 mg/kg/injection) decreased in a dose-related fashion after injections of the dopaminergic agonists apomorphine and piribedil. The dopaminergic agonists appear to suppress amphetamine intake in the same way as do 'free' amphetamine injections, by extending drug satiation in a given interresponse period. Clonidine, an alpha noradrenergic agonist, did not have similar effects. Apomorphine and piribedil did not increase 14C-amphetamine levels in rat brains, nor did they retard disappearance of 14C-amphetamine; thus their amphetamine-like effects are not due to alterations of amphetamine metabolism. Rats responding for amphetamine continued to respond for apomorphine or peribedil when the latter drugs were substituted for the former. Rats experienced in amphetamine self-administration readily initiated and maintained responding for apomorphine and piribedil. The dopaminergic blocker (+)-butaclamol disrupted responding for apomorphine and piribedil, although it produced no marked increase in responding for the dopaminergic agonists, as it does for amphetamine. These data add to the evidence that actions in the dopaminergic synapse account for amphetamine's reinforcing properties.

Amphetamine↗
PubMed1978

A comparison of four toxicology resources in respect to rates of retrieval and time required.

An evaluation was conducted fo four periodically updated poison control resources widely used by pediatricians, emergency room personnel, and poison information/control centers; i.e., Poisindex, ToxiFile, Clinical Toxicology of Commercial Products, and the National Clearinghouse for Poison Control Centers' cards. The frequency of finding entries for substances known to be involved in accidental pediatric ingestions, the extent of the content and management information, and the time required to obtain the information were determined for the four resources. Poisindex was more complete than the other resources. ToxiFile was more useful than the remaining two resources, although the latter should be useful in over 70% of accidental toxic ingestions by children.

Humans↗
PubMed1977

Concurrent intracranial self-stimulation and amphetamine self-administration in rats.

In a two-lever testing chamber, rats had concurrent access to intravenous amphetamine and brain stimulation reinforcers. Responding for each reinforcer was generally increased above baseline rates taken when only one reinforcer was available. Amphetamine stereotypy was observed, but did not interfere with rapid lever-pressing for brain stimulation.

Amphetamine↗
PubMed1977

Sodium and potassium levels in antacids.

The current sodium and potassium levels of commercial antacid products is reported; many of these products have been reformulated recently. The clinical importance of sodium and potassium content of antacids is discussed.

Antacids↗
PubMed1976

Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats.

Norepinephrine (NE) and dopamine (DA) receptor blockade differentially affected amphetamine self-administration. DA blockade (pimozide, 0.0625 to 0.5 mg/kg, or (+)-butaclamol, 0.0125 to 0.1 mg/kg) caused periods of increased rate of responding for amphetamine which were followed, in the case of higher doses, by response cessation. The response cessation produced by 0.5 mg/kg pimozide was not reversed by non-contingent amphetamine injections until well after the peak effect of the pimozide was over. When access to amphetamine injections was delayed until 4 h after animals received 0.5 mg/kg pimozide, rate of responding was elevated. Thus DA seems to be critically involved in mediation of the reinforcing effects of amphetamine. Alpha-NE blockade with phentolamine (2.5-10 mg/kg) produced dose-related decreases in responding; blockade with phenoxybenzamine (1.25-10 mg/kg) had no effect. Beta-NE blockade with l-propranolol (2.5-10 mg/kg) decreased responding, although probably not through a beta-blocking action. The effects of phentolamine and propranolol do not appear to result from attenuation of the reinforcing effects of amphetamine.

Animals↗
PubMed1976

Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats.

Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties.

Administration, Oral↗