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Biomedical subjects

J Church

Publications and source records attributed to J Church.

At least 91 records · Page 5Linked to original sources
PubMed1989

Electrophysiological properties of rat CA1 pyramidal neurones in vitro modified by changes in extracellular bicarbonate.

1. Intracellular recordings were made from the somata of CA1b hippocampal pyramidal neurones in vitro and the concentration of bicarbonate ion ([HCO3-]o) in the artificial cerebrospinal fluid (ACSF) was varied by substitution for Cl-. 2. Reducing [HCO3-]o from 26 mM (standard ACSF) to 8.6 mM or raising it to 72 mM had only minor effects on resting membrane potential but input resistance was reduced and increased, respectively. Threshold for Na(+)-dependent action potential generation was raised during the perfusion with low-HCO3- ACSF and lowered during perfusion with high-HCO3- ACSF. In tetrodotoxin-poisoned neurones where presumed Ca2(+)-dependent potentials could be elicited in standard ACSF, perfusion with high-HCO3- ACSF lowered the activation threshold. Where no Ca2(+)-dependent spikes could be elicited in standard ACSF, perfusion with high-HCO3- ACSF caused their appearance. Ca2(+)-dependent spikes could not be evoked during perfusion with low-HCO3- ACSF. 3. Depolarizing current pulses evoked two basic patterns of action potential discharge under standard [HCO3-]o conditions. Conversion between the two types was possible by varying [HCO3-]o. In those neurones which fired a train of fast Na(+)-dependent spikes in standard ACSF, perfusion with high-HCO3- ACSF usually led to the development of burst discharges. A smaller number of neurones responded to depolarizing current with an initial burst of three to six action potentials; the bursts were attenuated in low-HCO3- ACSF and replaced by a repetitive spike discharge. Frequency accommodation of spike discharge in response to depolarizing current pulses and the after-hyperpolarization following a current-evoked discharge were usually both attenuated in low-HCO3- ACSF and enhanced in high-HCO3- ACSF. 4. Orthodromically evoked excitatory postsynaptic potentials (EPSPs) and early and late inhibitory postsynaptic potentials (IPSPs) were reduced in amplitude during perfusion with low-HCO3- ACSF. In high-HCO3- ACSF, EPSP amplitude and duration increased, the latter reflecting a positive shift in the reversal potential of the early IPSP consequent upon reduced [Cl-] in high-HCO3- ACSF. The late IPSP was, however, unaffected. 5. Responses to ionophoretically applied excitatory amino acids were enhanced in high-HCO3- ACSF and depressed in low-HCO3- ACSF. 6. Perfusion with high-HCO3- ACSF was associated with the development of epileptiform activity. Spontaneous or synaptically evoked bursts of action potentials were indistinguishable and could be blocked by N-methyl-D-aspartate antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Antitussive agents as N-methylaspartate antagonists: further studies.

The relative potencies of ketamine and the morphinan derivatives dextrorphan, dextromethorphan, and levorphanol as antagonists of the excitatory actions of N-methylaspartate on rat spinal neurones in vivo were examined, both following their microelectrophoretic administration and, with the exception of levorphanol, after intravenous injection. Applied microelectrophoretically, dextrorphan was a more potent N-methylaspartate antagonist than ketamine, levorphanol, or dextromethorphan. After systemic administration, however, dextrorphan was rather less potent than ketamine in this respect, whereas dextromethorphan remained less potent than either ketamine or dextrorphan. Noscapine, an antitussive that lacks anticonvulsant activity, failed to reduce selectively responses to N-methylaspartate as did papaverine, an isoquinoline structurally related to noscapine, and triprolidine, an antihistamine commonly found in proprietary cough medicines. The results are discussed with particular reference to the potential of the compounds tested as anticonvulsant and neuroprotective agents in vivo.

Animals↗
PubMed1988

Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands.

We have used microelectrophoretic and intravenous administration of drugs to rat spinal cord neurones in vivo and bath application to rat cortical wedges in vitro to evaluate MK-801 and other phencyclidine (PCP) receptor ligands as N-methylaspartate (NMA) antagonists, paying particular regard to the possible use-dependent nature of their action. MK-801, 0.1-0.5 mg/kg, was a selective and long-lasting NMA antagonist. We were unable to demonstrate significant use-dependent onset of antagonism of NMA by any of the drugs in vivo. Recovery, however, for MK-801 was use-dependent. In vitro there was a gradation with MK-801 being very use-dependent, followed by (PCP), cyclazocine and ketamine, the last showing little or no use-dependence. Results of experiments modulating the in vitro environment suggest that a significant difference between the in vitro and in vivo systems was temperature. Raising the temperature of the wedge chamber from 23 to 33 degrees C reduced the use-dependence of MK-801, and lowering the temperature to 13 degrees C increased the use-dependence of PCP. The mechanism of action of PCP receptor ligands is discussed in the light of these results.

Animals↗
PubMed1988

The neuroprotective action of ketamine and MK-801 after transient cerebral ischemia in rats.

The neuroprotective activity of two systemically administered N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine and MK-801, were investigated in a long-term recovery model of near-complete forebrain ischemia in the rat. Doses of each drug were chosen on the basis of the known degree and time course of NMDA antagonism seen in vivo after their systemic administration. Ketamine, administered at a dose of 20 mg.kg-1 iv, either immediately before or shortly after the 10-min ischemic period, failed to lessen neuronal damage in the selectively vulnerable hippocampal CA1 region. Increasing doses of ketamine administered over an increasing length of time in the postischemic period, however, did provide significant protection. MK-801 0.25 or 0.5 mg.kg-1 iv administered before ischemia also resulted in significant protection. The results support the proposal that NMDA receptor-mediated events may contribute to neuronal damage in selectively vulnerable regions of the central nervous system after ischemia.

Animals↗
PubMed1987

Non-pharmacological effects of the use of microelectrophoresis and pressure ejection of drugs in combination.

Pressure ejection of physiological saline from multibarrel micropipette assemblies has been shown to selectively reduce responses of rat spinal cord neurones to electrophoretic ejection of kainate, N-methyl-aspartate and 4-methyl-homoibotenate, but not of quisqualate or L-glutamate. Reduction of response to an excitatory amino acid therefore appears to be correlated with the absence of an active transport system for that amino acid.

Amino Acids↗
PubMed1987

Transplacental stimulation of fetal lung maturation: effect of triiodothyronine in the female and male rabbit fetus.

We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.

Animals↗
PubMed1986

Is Metaphit a phencyclidine antagonist? Studies with ketamine, phencyclidine and N-methylaspartate.

The dissociative anaesthetics, phencyclidine and ketamine, block excitation of central neurones by N-methylaspartate. Using the technique of microelectrophoresis on rat spinal neurones in vivo Metaphit, a phencyclidine receptor acylating agent, was tested to see whether it would antagonise this effect of dissociative anaesthetics. The predominant effect of Metaphit was, however, to reduce N-methylaspartate induced excitation. It is concluded that Metaphit has mixed agonist/antagonist effects at the phencyclidine receptor.

Action Potentials↗
PubMed1986

Effects of low fat diets varying in P/S ratio on nutrient intakes, fecal excretion, blood chemistry profiles, and fatty acids of adult men.

Twenty-three apparently healthy volunteers aged 35 to 60 years consumed closely monitored self-selected (SS) diets for five weeks followed by two low fat controlled diets (25% energy) for two six-week periods followed by another five-week SS diet. The two low fat diets, fed in a crossover design to one-half of the subjects per controlled diet period, had a polyunsaturated/saturated (P/S) fat ratio of either 0.3 or 1.0. Results are reported for bi-weekly measurements of energy and nutrients; blood profiles and plasma fatty acids; and for end-of-period values for stool characteristics. Blood chemistry profiles differed in the two groups. The low P/S diet produced significant increases not only in cholesterol, but in 16:0, 16:1, and percent saturated fatty acids and decreases in 18:2 and omega 6 fatty acids. The reverse was seen with the high P/S diet. The essential fatty acid (EFA) linoleic acid returned in the poststudy period to prestudy levels (all subjects), but arachidonic acid did not. The explanation for negative correlation between magnesium intake or excretion and percent plasma linoleic acid must await further research.

Adult↗
PubMed1985

Differential effects of dextrorphan and levorphanol on the excitation of rat spinal neurons by amino acids.

The effects of the stereoisomers dextrorphan and levorphanol on the excitation of spinal neurons by electrophoretically administered excitatory amino acids were studied in pentobarbitone-anaesthetised rats. Both isomers reduced responses to N-methyl-DL-aspartate (NMA), dextrorphan being both more selective and more potent than levorphanol in this respect. This observation supports the proposal that the NMA-blocking activity of a variety of drugs with psychotomimetic properties is subserved by actions at phencyclidine (PCP)/sigma opiate receptors.

Acetylcholine↗