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Biomedical subjects

E J White

Publications and source records attributed to E J White.

13 recordsLinked to original sources
PubMed1991

Protection of ischaemic synaptosomes from calcium overload by addition of exogenous lactate.

In depolarised anoxic synaptosomes, in which lactate production was significantly raised compared with normoxic conditions, calcium uptake, net acetylcholine release, and the intrasynaptosomal calcium concentration were all significantly lowered. In contrast, lactate production in synaptosomes incubated under aglycaemic- and ischaemic-type conditions was significantly lower and basal calcium uptake, acetylcholine release, and intrasynaptosomal calcium concentration were elevated compared with normoxia. In addition, the increase in intrasynaptosomal calcium concentration under the ischaemic-type condition appeared to be greater than could be accounted for by the rise in calcium uptake alone. Intrasynaptosomal pH reflected the lactate production under each condition investigated. Addition of exogenous lactate to normoxic synaptosomes mimicked the effects observed in anoxia, suggesting that lactate itself may have blocked the calcium uptake, inhibiting the rise in intrasynaptosomal calcium and acetylcholine release occurring in depolarised anoxic synaptosomes. When lactate was added to ischaemic synaptosomes, the large rise in intrasynaptosomal calcium concentration, calcium uptake, and acetylcholine release were decreased, suggesting that lactate may have a protective role in preventing cell death by calcium overload under ischaemic-type conditions. Evidence is presented to suggest that the effect of L-lactate was due to the lactate moiety itself rather than the associated acidosis.

Acetylcholine↗
PubMed1990

Involvement of lactic acidosis in anoxia-induced perturbations of synaptosomal function.

L-Lactate (4-32 mM) added exogenously to resting or depolarised rat forebrain synaptosomes led to a significant decrease in intrasynaptosomal pH. Similarly depolarisation-induced increases in intrasynaptosomal calcium, calcium uptake, and acetylcholine release were all inhibited. These effects mimicked those previously observed in synaptosomes under anoxic conditions and suggest that lactate may be involved in limiting the damage due to calcium accumulation occurring during ischaemia. D-Lactate (added exogenously up to 32 mM) did not produce similar effects on these parameters even though the concentrations of intrasynaptosomal D-lactate reached levels comparable to those obtained with L-lactate (at 8-16 mM exogenous concentration). The results suggest that the mechanism of action of lactate on these parameters is stereospecific for the L-enantiomer. The effect of glucose availability on lactate production was assessed to explore the role of substrate availability on ischaemia/anoxic events. When exogenous glucose was increased (10-60 mM), there was no further increase in lactate production in normoxic synaptosomes, which suggests that glucose is not limiting under these conditions. When glucose was removed, as may occur in complete ischaemia, there was a significant decrease in lactate production after 60 min under anoxic or normoxic conditions. It would seem likely therefore that the mechanism underlying the changes observed in synaptosomes incubated under conditions reflecting complete ischaemia does not involve lactate.

Acidosis, Lactic↗
PubMed1989

Effects of lactic acidosis on the function of cerebral cortical synaptosomes.

Synaptosomes exposed to anoxic insult produce lactate at a slow rate (measured over 60 min). No measurable damaging effects were produced by prolonged depolarisation, anoxic insult, or exogenous lactate (2-32 mM) either on the synaptic plasma membrane (as judged by release of lactate dehydrogenase and soluble proteins), or on synaptosomal phospholipases (as judged by choline release from membrane phospholipids). Potassium-stimulated acetylcholine release was decreased by incubation in the presence of lactate (2-32 mM), as was potassium- and veratrine-stimulated calcium uptake and the calcium content of depolarised synaptosomes. The intrasynaptosomal pH was also reduced but there was no stimulation of oxygen radical production (as judged by H2O2 generation) by exogenous lactate. The role that lactic acidosis may play in giving rise to the altered calcium homeostasis and decreased acetylcholine release from synaptosomes exposed to anoxic insult is discussed.

Acetylcholine↗
PubMed1988

Menadione-treated synaptosomes as a model for post-ischaemic neuronal damage.

Menadione bisulphite increased endogenous oxygen-radical production by rat brain synaptosomes, as indicated by H2O2 generation. Increased oxygen-radical production was also demonstrated in synaptosomes prepared from menadione-treated rats and synaptosomes reoxygenated after an anoxic insult. Acetylcholine synthesis de novo was inhibited in synaptosomes incubated with menadione in vitro, in synaptosomes prepared from menadione-treated animals in vivo, and in depolarized post-anoxic synaptosomes. Intrasynaptosomal free Ca2+ was increased by menadione in vitro (50 microM), but this increase was not due to stimulation of Ca2+ entry into the nerve terminals. Acetylcholine release was stimulated by menadione in vitro, possibly as a consequence of the elevated intrasynaptosomal Ca2+ content. The Ca2+ contents of synaptosomes prepared from menadione (10 mg/kg)-treated animals in vivo and synaptosomes reoxygenated after anoxia were unchanged. In synaptosomes prepared from menadione-treated animals, acetylcholine release was no longer significantly stimulated by K+, whereas it was unchanged from control (normoxic) values in synaptosomes reoxygenated after anoxia. None of these treatments caused any measurable damage to the synaptic plasma membrane (as judged by the release of lactate dehydrogenase), or to synaptosomal phospholipases (as judged by choline release from membrane phospholipids). Synaptosomes prepared from menadione-treated rats were found to be a good model for the study of post-anoxic damage to nerve-terminal function.

Acetylcholine↗
PubMed1988

Streamlining operation of an admitting service for interventional radiology.

The authors describe how operations of an inpatient admitting service for interventional radiology were improved by developing a clinic and hiring a physician's assistant. The service, begun in 1982, was managed by a senior radiologist and fellows. Because of increasing admissions (from a mean of 52 per year in 1982-1985 to 110 per year in 1985-1987), a 1/2-day, twice-weekly clinic was created in 1985 to evaluate new patients and perform follow-up examinations. In 1986 a physician's assistant was hired to assist in the clinic and during patient admissions. Use of the clinic and physician's assistant streamlined patient flow and management during hospitalization. This resulted in a decrease in mean length of stay for patients undergoing angioplasty (from 3.74 days in 1982-1983 to 2.41 days in 1986-1987). This decrease means cost savings for the hospital under the prospective payment system. Other benefits include improved physician-patient relationships and follow-up, new patients for colleagues (15% of patients had anatomy unsuitable for interventional procedures and were referred to staff surgeons), and increased professional fees.

Angioplasty, Balloon↗
PubMed1986

Participation of intracellular sites in the action of Ca2+ channel blockers.

The action of phenylalkylamine Ca2+ channel blockers D890 and D888 on Ca2+ uptake and neurotransmitter amino acid release were studied. D890, the quaternary derivative of D600, did not inhibit veratrine-induced 45Ca2+ uptake or the release of neurotransmitter amino acids from rat cerebrocortical synaptosomes, except at high concentrations (200 microM) when it was probably acting extracellularly in a non-specific manner. This contrasted with the more potent (10-50 microM) inhibitory actions of D600 and D888, and may be due to the inability of D890 to cross the synaptic plasma membrane. (-)D888 was shown to cross cell membranes and accumulate in the intracellular compartment of cerebrocortical slices and synaptosomes, where it was associated predominantly with the soluble cytoplasmic fraction.

Amino Acids↗
PubMed1986

Enhancement of depolarization-induced synaptosomal calcium uptake and neurotransmitter release by Bay K8644.

Ca2+ uptake into submaximally stimulated synaptosomes was augmented by low concentrations of BAY K8644 (0.1-100 nM). Use of either veratrine or potassium as the depolarizing agent produced similar effects. Stimulated release of aspartate, glutamate and GABA was enhanced over a similar concentration range of BAY K8644. The extent of synaptosomal depolarization induced by veratrine was not enhanced by BAY K8644. The results are discussed in relation to BAY K8644 activation of voltage-dependent Ca2+ channels in neural tissue. This is the first report of BAY K8644 acting on synaptosomes at concentrations that correlate to dihydropyridine binding studies.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Inhibitory actions of opioid compounds on calcium fluxes and neurotransmitter release from mammalian cerebral cortical slices.

The effects of opioid agonists on veratrine-stimulated Ca2+ influx and amino acid neurotransmitter release in rat cerebrocortical brain slices were studied. Inhibitory effects were seen on both of these parameters with all of the opioid agonists used. None of the drugs used affected basal 45Ca2+ uptake, basal K+ content or basal amino acid release from the slices. At high concentrations (100 microM) fentanyl, tifluadom, U50,488H, butorphanol and bremazocine greatly inhibited the depolarization of the slices by veratrine as determined by the reduced release of K+. The opioid receptor subtypes at which the drugs were acting were characterized by the antagonistic effects of naloxone and WIN44441-3. The opioid-induced inhibition of stimulated Ca2+ uptake and amino acid release were not antagonized by WIN44441-2, the inactive enantiomer of WIN44441-3. It is concluded that opioid agonists acting through mu- and kappa-receptors and probably through delta- and sigma-receptors, have an inhibitory effect on Ca2+ uptake into cerebrocortical brain slices and the subsequent release of aspartate, glutamate and gamma-aminobutyric acid (GABA).

Amino Acids↗