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M J Halsey

Publications and source records attributed to M J Halsey.

At least 73 records · Page 4Linked to original sources
PubMed1986

Sperm maturation associated with subfertility following hyperbaric exposure of mice.

Mice exposed to 50 ATA heliox pressure during one spermatogenic cycle subsequently exhibit subfertility which can recover over an 8-wk period. This study was designed to investigate the changes in spermatid and testicular histology associated with these phenomena. Electron microscopy of testicular tissue from hyperbaric-exposed animals revealed a significant effect on spermatogenesis including disorganization and patchy necrosis of the epithelium. Two weeks after exposure to pressure, abnormalities were more difficult to find and tissues taken from animals 8 wk after exposure were indistinguishable from normal. These data directly confirm our earlier hypothesis that chronic hyperbaric exposure has a deleterious effect on sperm maturation, which is subsequently manifest as a failure in fertilizing capacity.

Animals↗
PubMed1985

General and local anaesthetics perturb the fusion of phospholipid vesicles.

The effects of general and local anaesthetics on Ca2+-induced fusion of negatively charged lipid vesicles have been investigated. Vesicles composed of phosphatidylcholine and phosphatidic acid (2:1 molar ratio) were induced to fuse using 5 mM free Ca2+. Fusion, assessed by an increase in size using gel filtration techniques and confirmed by electron microscopy, displayed a dependence on Ca2+ and Mg2+ concentration and on temperature. The inhalational anaesthetics halothane, methoxyflurane and diethyl ether enhanced fusion as did the uncharged local anaesthetic benzocaine. In contrast, the charged local anaesthetics lignocaine and bupivacaine inhibited the fusion process. It is suggested that the enhancement observed with the inhalational anaesthetics and benzocaine was mediated by an effect on lipid fluidity and the inhibition observed with the charged tertiary amine anaesthetics was due to an antagonism towards Ca2+.

Anesthetics↗
PubMed1985

Mixtures of inhalation and i.v. anaesthetics at high pressure. A test of the multi-site hypothesis of general anaesthesia.

We have tested the hypothesis that anaesthetics having different pressure reversal characteristics act at different molecular sites with finite capacities and, therefore, do not necessarily have additive potencies when used in mixtures of varying composition. The additivity of the anaesthetic potencies has been tested at normal pressures and at pressures up to 100 ATA for eight combinations of the following mixtures: Althesin plus nitrous oxide; methohexitone plus nitrous oxide; thiopentone plus nitrous oxide; thiopentone plus propanidid. The anaesthetic potencies of the first two mixtures were not additive at increased pressures, whereas those of the latter two mixtures were additive. These data support the multi-site hypothesis of general anaesthesia.

Alfaxalone Alfadolone Mixture↗
PubMed1984

The high pressure neurological syndrome and 2-amino-7-phosphonoheptanoic acid: differences between fed and fasted rats.

The elevated atmospheric pressure at which the main features of the high pressure neurological syndrome (HPNS), i.e. tremor, myoclonus and convulsions, successively appear, have been studied in fed and fasted rats with and without pretreatment with 2-amino-7-phosphonoheptanoic acid (180 mg/kg). The onset pressure for tremor is lower in fasted rats. 2-Amino-7-phosphonoheptanoic acid raises the onset pressure for all three phases of HPNS in fed rats, but only for tremor and convulsions in fasted rats. The results are interpreted in terms of changes in aspartergic and related excitatory neurotransmission.

2-Amino-5-phosphonovalerate↗
PubMed1984

Specific effects of drugs at pressure: animal investigations.

The interactions of anaesthetics and other drugs with high pressure suggest that protection against the high pressure neurological syndrome (h.p.n.s.) can no longer be considered in terms of generalized non-specific mechanisms. The evidence from our work shows that anaesthetics may either protect, have no effect, or potentiate h.p.n.s. Structural analogues of the steroid anaesthetic Althesin have a protective effect against high pressure tremors in spite of the fact that they have no anaesthetic effects. Low doses of flurazepam are effective against tremor but can be antagonized by Ro 15-1788, which implies in this case a role for the benzodiazepine receptor complex. Pressure interactions with other drugs have included the classic anticonvulsants--which, in general, were relatively ineffective--and various agents perturbing the balance of specific neurotransmitter systems. Representative examples from different studies include 6-hydroxydopamine, muscimol, and sodium valproate. Finally, the potent protection against h.p.n.s. by 2-amino-phosphonoheptanoic acid, an antagonist with preferential action against excitation produced by aspartate and N-methyl-D-aspartate, provides the first evidence that enhanced excitatory amino acid neurotransmission may have an important role in the h.p.n.s.

Amino Acids↗
PubMed1984

A reassessment of the molecular structure-functional relationships of the inhaled general anaesthetics.

The importance of structure-activity relationships in the inhaled general anaesthetic agents may have been underestimated in the elucidation of the central and peripheral mechanisms of general anaesthesia. It is true that there is no single spatial arrangement of atoms in a molecule that is essential for anaesthetic activity; the "anesthesiophore", as it was termed, is a myth. However, the chemical structure of a compound is directly related to its physical properties which in turn are one of the major determinants in the molecular mechanisms. Second, chemical structures are the major factors in the physical, chemical and biological stability of the anaesthetics; in particular the electron distributions, bond densities and net atomic charges determine the extent and mode of biotransformation. Some of the evidence for the importance of structure in the anesthetic "side effects" on circulation, respiration and neuroelectric irritability is presented. An example of the detailed structural-molecular studies is provided by the nuclear magnetic resonance investigations of anaesthetic conformational perturbations of haemoglobin which we have used as a model system for elucidating the ground rules of anaesthetic-protein interactions.

Anesthesia, Inhalation↗
PubMed1983

Non-anesthetic steroids ameliorate the high pressure neurological syndrome in rats.

The hypothesis that non-anaesthetic compounds, structurally related to specific anaesthetics, can protect against the high pressure neurological syndrome was tested. Infusion of two structural analogues of alphaxalone (3 alpha-hydroxy-5 alpha pregnane-11,20 dione) during pressurisation of rats with helium and oxygen gas mixtures (total pressure 80-100 ATA; inspired oxygen partial pressure 0.5 ATA) ameliorated the severe tremors associated with the high pressure neurological syndrome without any shift in tremor frequency (11-14 Hz). The steroid analogues which were selected (delta 16 and 3 beta-hydroxy-alphaxalone) have no known general anaesthetic effects and present an unexpected structural approach to the pharmacology of the syndrome. It may now be possible to investigate, treat or prevent the syndrome by the use of selective drugs without more generalised anaesthetic effects.

Alfaxalone Alfadolone Mixture↗
PubMed1983

Interactions of gamma-aminobutyric acid and noradrenaline in the high pressure neurological syndrome.

The effects on the high pressure neurological syndrome (HPNS) of reducing brain noradrenaline (NA) levels were studied in adult rats. The onset of tremors and convulsions, which occur as pressure is increased, were used as endpoints for assessing the onset and severity of the HPNS. Neonatal treatment with 6-hydroxydopamine (6-OHDA; 100 mg kg-1 i.p. alternate days from birth for 2 weeks) which depleted brain NA, produced no change in the HPNS as assessed by the appearance of tremors and convulsions. A second series of NA-depleted rats and equivalent controls were treated with a GABA agonist, muscimol, 0.1 microgram intracerebroventricularly. Subsequently the rats were exposed to pressure and the onset and severity of the HPNS was assessed by observation of tremors and convulsions. A combination of NA depletion and intracerebroventricular injection of muscimol significantly raised the onset pressures for tremors and convulsions, i.e. delayed the appearance of the HPNS. These results are consistent with the HPNS being associated with a disturbance in the balance of two or more neurotransmitter systems, rather than simply an increase or reduction in levels of a single transmitter.

Aminobutyrates↗
PubMed1983

Assessment of recovery from hyperbaric-induced subfertility in male mice.

This study was designed to investigate whether subfertility in male mice produced by exposure to high pressures of heliox showed any recovery. Male mice were exposed to 50 ATA heliox (controls exposed to 1 ATA air) during one spermatogenic cycle; subsequently each male was housed with 10 untreated females. After 14 days males were removed and housed with 10 more females. This was repeated four times. Male libido, pregnancy rate, pre- or early implantation loss, and fetal survival were determined for each mating. Results showed that all variables were significantly reduced in the pressure group during the first mating, but there were differing rates of recovery. Male libido was consistently reduced (12%) and showed no recovery trend. Pregnancy rate showed continuing improvement throughout all matings but did not reach control levels after 8 wk. Pre/early implantation loss and fetal survival had returned to control values by the fourth mating. These data suggest that pressure-induced subfertility is largely reversible, and at least two separate events contribute to it.

Animals↗
PubMed1982

Chronic exposure of rats to enflurane 200 p.p.m.: no evidence of toxicity or teratogenicity.

Adult male or female rats were exposed either to enflurane 200 p.p.m. or to air for up to 63 days before mating and subsequently throughout the pregnancy of the females. The treated animals were exposed for 8 h per day, 5 days per week for a maximum total of 100 days. The parents and progeny-were studied. Additional positive controls with vitamin A palmitate demonstrated that the strain of animals was susceptible to a known teratogen. No abortifacient effect was observed with these conditions of exposure to enflurane. Skeletal examination of the fetuses failed to reveal any major teratogenic effect. The parents remained healthy clinically, whilst autopsy and histopathological examination failed to reveal any consistent organ injuries which could be blamed on exposure to enflurane. In rats at least, environmental pollution with enflurane appears not to be associated with significant toxicity or teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1982

Hydrogen bonding in mechanisms of anaesthesia tested with chloroform and deuterated chloroform.

There has been recent speculation about the role of hydrogen bonding in molecular mechanisms of anaesthesia. We have tested this hypothesis by comparing the potencies of chloroform and deuterated chloroform in mice, using loss of righting reflex as the endpoint for anaesthesia. We found that the ED50 for chloroform was 0.297 +/- 0.03% (SD) and for deuterated chloroform 0.318 +/- 0.02% (SD). These values are not significantly different. However, there were some differences in toxicity with deuterated chloroform having less "acute" toxicity. This is compatible with an isotope effect in which deuterium interferes with the formation of reactive free radicals. We conclude from the potency data that hydrogen bonding can be excluded as the major mechanism of chloroform anaesthesia.

Anesthesia, Inhalation↗
PubMed1982

Reduction in fertility of male mice after exposure to high environmental pressure.

Male mice were exposed to 50 ATA heliox pressure to study whether their functional fertility was affected. In series I, control mice were exposed to 1 ATA air; in series II controls were exposed to 5 ATA heliox, which enabled the PO2 and environmental temperature to be maintained at equivalent levels to the pressure group. After exposure during one spermatogenic cycle, the mice were mated with untreated females. There was a dramatic reduction in fertility in the pressure groups, with males in both series I and II showing a 65% reduction in fertility. Overall results were as follows: 19.5% pregnant females mated with the pressure groups compared with 55% pregnant in the control groups. Litter sizes in the pressure groups were reduced by 44%, but there was no evidence of any pressure-related teratological effect. This reduction in fertility appears to be due to high pressure per se and not to the high environmental temperature and PO2 associated with heliox atmospheres.

Animals↗
PubMed1981

Applied physical chemistry for clinical anaesthetists.

Physical chemistry is applicable to many aspects of both clinical anaesthesia and research. This review includes applications in: (a) the supply of gases and vapours; (b) some drug interactions, particularly at the site of absorption; (c) the uptake and distribution of the agents; and (d) mechanisms of anaesthesia based on correlations with physical properties.

Anesthesiology↗
PubMed1981

Molecular mechanisms of anaesthesia: do they matter?

The study of the critical molecular changes in general anaesthesia is one of the alternative approaches to the central mechanisms. It complements the neurophysiological studies and the work on isolated nerves or subcellular synaptic components. The current concept of molecular actions of anaesthetics is that the agents are present in both the lipid and protein components of the neural membranes. The proteins control the various functions of the membranes and the lipid environments indirectly affect the proteins. Different anaesthetics have different critical sites of action. The basic studies have resulted in a number of clinical applications, including the additivity of potencies and drug interactions.

Acetylcholine↗