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Biomedical subjects

M R Vasko

Publications and source records attributed to M R Vasko.

6 recordsLinked to original sources
PubMed1992

Prostaglandin E2 increases calcium conductance and stimulates release of substance P in avian sensory neurons.

Prostaglandins are known to lower activation threshold to thermal, mechanical, and chemical stimulation in small-diameter sensory neurons. Although the mechanism of prostaglandin action is unknown, agents known to elevate intracellular calcium produce a sensitization that is similar to that produced by prostaglandins. Consistent with the idea of prostaglandin-induced elevations in calcium, prostaglandins might also stimulate the release of neurotransmitter from sensory neurons. We therefore examined whether prostaglandin E2 (PGE2) could enhance the release of the putative sensory transmitter substance P (SP) from isolated neurons of the avian dorsal root ganglion grown in culture. Utilizing the whole-cell patch-clamp recording technique, we also examined whether PGE2 could alter calcium currents in these cells. Exposure of sensory neurons to PGE2 produced a dose-dependent increase in the release of SP. One micromolar PGE2 increased release approximately twofold above basal release, whereas 5 and 10 microM PGE2 increased release by about fourfold. The release evoked by these higher concentrations of PGE2 was similar in magnitude to the release induced by 50 mM KCl. Neither arachidonic acid (10 microM), prostaglandin F2 alpha (10 microM), nor the lipoxygenase product leukotriene B4 (1 microM) significantly altered SP release. The addition of 1 microM PGE2 increased the peak calcium currents by 1.8-fold and 1.4-fold for neurons held at potentials of -60 and -90 mV, respectively. The action of PGE2 was rapid with facilitation occurring within 2 min. As with release studies, arachidonic acid, prostaglandin F2 alpha, and leukotriene B4 had no significant effect on the amplitude of the calcium current. These results suggest that PGE2 can stimulate the release of SP through the activation or facilitation of an inward calcium current. The capacity of PGE2 to facilitate the calcium current in these sensory neurons may be one mechanism to account for the ability of prostaglandins to sensitize sensory neurons to physical or chemical stimuli.

Animals↗
PubMed1979

Lorazepam in status epilepticus.

Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.

Adolescent↗
PubMed1979

Barbitone-induced tolerance to the effects of sedative-hypnotics and related compounds on operant behaviour in the rat.

1 Pretreatment doses of barbitone, pentobarbitone, ethanol, and phenytoin (diphenylhydantoin) in non-tolerant rats produced increases in operant responding at low doses and at higher doses resulted in decreases in responding.2 Daily barbitone injections (100 mg/kg, i.p.) resulted in the development of functional tolerance to both the stimulant and depressant effects of barbitone on responding.3 Barbitone tolerance development did not result in any change in the brain or plasma pharmacokinetics of barbitone.4 Barbitone-tolerant rats were cross-tolerant to the behavioural effects of pentobarbitone, ethanol, and phenytoin. The dose-effect curves for all of these drugs were shifted to the right in tolerant rats, compared to non-tolerant rats.5 Comparison of the brain and plasma levels of these drugs in non-tolerant and tolerant rats provided a means of separating functional cross-tolerance from dispositional cross-tolerance. Barbitone-tolerant rats appeared to be functionally cross-tolerant to ethanol in that there was no change in the brain and blood ethanol levels at times when the degree of behavioural impairment was substantially reduced. In contrast to ethanol, cross-tolerance to phenytoin appeared to be due to a decrease in the brain and plasma levels (dispositional tolerance). Cross-tolerance to pentobarbitone appeared to be comprised of both functional and dispositional cross-tolerance.6 The usefulness of a multidisciplinary approach in the analysis of sedative hypnotic tolerance and cross-tolerance is discussed. It is concluded that without the concurrent determination of both brain and plasma drug levels it would not be possible to distinguish between functional and dispositional tolerance.

Animals↗
PubMed1978

Tolerance development to the biphasic effects of morphine on locomotor activity and brain acetylcholine in the rat.

The development of tolerance to the depressant and stimulant actions of morphine on locomotor activity and brain acetylcholine (ACh) utilization (indirect turnover) was investigated in the rat. When administered to nontolerant rats, 1.0 mg/ kg s.c. of morphine produced an increase in locomotor activity and a concomitant increase in ACh utilization. Larger doses produced biphasic effects on locomotor activity, but only 10 mg/kg s.c. resulted in both an initial decrease and subsequent increase in ACh utilization in whole rat brain. The depressant and stimulant actions of morphine on both endpoints were antagonized by 1.0 mg/kg i.p. of naloxone administered 30 min before the maximum effect. Tolerance to morphine was produced by t.i.d. injections of increasing doses. Rapid tolerance developed to the locomotor depressant actions of morphine and to the decrease in brain ACh utilization. Tolerance to the depressant effects resulted in an enhanced stimulant action. Tolerance also developed to the stimulant actions of morphine but only when large doses of drug were administered daily. Biphasic effects of 10 mg/kg of morphine on brain ACh utilization were also observed in the hippocampus, thalamus and hypothalamus. Only a decrease in ACh utilization was observed in the caudate nucleus. Tolerance developed to the decreases and increases in ACh utilization in these discrete brain regions. This study demonstrates that tolerance development to the depressant and stimulant actions of morphine is complex and involves different dose and time schedules. It is not possible therefore to study tolerance to the actions or morphine without specifying the precise endpoint studied and the tolerance schedule utilized.

Acetylcholine↗
PubMed1977

The use of filtration techniques for the lysis and study of red blood cells.

A filtration technique for the gentle lysis of erythrocytes has been developed using cellulose triacetate membranes. When cell suspensions are filtered under nitrogen pressure, lysis occurs at the surface of the filter in such a way that the cell ghosts are retained on the filter. The contents of the cell are extruded through the pores of the filter without mixing with the cell suspension. Cell ghosts and intact erythrocytes have been collected on membranes and examined by electron microscopy. These preparations have the advantage of being free of the structural artifacts that result from centrifugation. In addition, the filter facilitates preparation for electron microscopy by providing a support for the sample during fixation and then dissolving during the dehydration of the sample.

Animals↗