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Biomedical subjects

S E Freeman

Publications and source records attributed to S E Freeman.

66 records · Page 4Linked to original sources

Ionic interactions in acetylcholine contraction of the denervated rat diaphragm.

1. The nature of the drug-receptor interaction in the acetylcholine-induced contraction of the denervated rat diaphragm was studied both by altering the external ionic environment and by determining its drug sensitivity.2. The response to acetylcholine was insensitive to tetrodotoxin or saxitoxin, but was abolished by procaine.3. It was unaffected by levels of MnCl(2) sufficient to block the response of the innervated diaphragm to electrical stimulation, although higher levels reduced the response. The effect of Mn(++) on the innervated diaphragm was overcome by raising the external Ca(++) level; this was ineffective in the denervated preparation.4. In spite of its insensitivity to tetrodotoxin the acetylcholine contraction was reduced and prolonged by low external Na(+) levels. This prolongation was not found when Li(+) substituted for Na(+).5. Increasing the external level of Ca(++) or Mg(++) 3 to 5-fold reduced the acetylcholine contraction; high Ca(++) also prolonged it. Reduction in the divalent cation level was without effect.6. Procaine inhibition of the acetylcholine response was largely competitive, as was inhibition due to (+)-tubocurarine. This was shown by probit analysis and the dose-ratio test.7. Thiocyanate (12 mM) augmented and prolonged the contraction; this action was modified by altering the Ca(++) or Mg(++) level of the solution.8. The acetylcholine receptor resembles that of the innervated postsynaptic membrane.

Acetylcholine↗

A pharmacological study of the toxin in a Cnidarian, Chironex fleckeri Southcott.

1. A study has been made of the pharmacological actions of toxic preparations obtained from the box jellyfish Chironex fleckeri Southcott. Two toxin preparations were used. One was a tentacle extract which was partially purified by Sephadex gel filtration; the second was obtained by a process analogous to snake milking, and is probably similar in composition to the material injected into victims.2. All preparations were extremely toxic; death in animals, following minimally lethal doses, occurred in minutes. Respiratory arrest of central origin appeared to be the terminal event in all species tested. This was accompanied by marked signs of cardiotoxicity. The heart was slowed, irregular, and showed varying degrees of conduction delay. Terminally it showed atrioventricular block.3. Blood pressure changes were biphasic. An initial rise in carotid pressure was followed by a profound fall; a second rise to an above normal level frequently followed this. These blood pressure oscillations were damped down by prior treatment with hexamethonium but the hypertensive response remained.4. Blood samples taken before terminal apnoea showed a variable degree of haemolysis and a raised K(+) level.5. Experiments with isolated organ preparations suggested that the toxin had a non-specific lytic effect on cells, but did not contain pharmacologically active substances of small molecular weight such as 5-hydroxytryptamine.6. It is suggested that the toxin(s) act by altering membrane permeability; the signs at death may reflect the sensitivity of the target organs to such a change.

Animals↗

Serum effects on DNA repair in human cells.

Freshly isolated human lymphocytes were used to determine how serum supplements affect cellular capacity to repair UV damage. Repair capacity was always found to be greatest in medium supplemented with autologous plasma. Variability in repair capacity among individuals was greater in serum supplemented medium than in unsupplemented medium. Thus, in vitro cellular responses will most accurately represent in vivo responses if autologous serum factors are present in the culture medium. This is of particular importance in studies attempting to correlate DNA repair capacity with age or susceptibility to carcinogenesis.

Adult↗

Present state of control of chemical and biological weapons.

The use of chemical and biological weapons in war is prohibited by the Geneva Protocol of 1925 and the Biological Weapons Convention of 1972. Currently a new Chemical Weapons Convention is being negotiated in the UN Conference on Disarmament in Geneva. When this Convention enters into force the production, stockpiling and retention of chemical weapons will be prohibited. The development of a body of international law will enable the verifiable destruction of weapons such as these, and should lead to a more general programme of disarmament.

Biological Warfare↗

The biological hazards of plutonium.

The health hazards associated with exposure to low levels of plutonium are reviewed since, though the world may escape a nuclear war, there may be virtually permanent contamination of the biosphere by plutonium from a number of sources. It would seem that it is possible to offer workers in the nuclear industry an acceptable level of protection but that low levels of pollution around such sites may build up until there is a hazard for people in the vicinity. The cases of childhood leukaemia found in the vicinity of the Sellafield facility may or may not be related to contamination in the area; however, plutonium is a potent carcinogen, and the foetus seems to be particularly vulnerable to it. The disposal of nuclear waste must be monitored more closely, and it is suggested that the International Atomic Energy Agency should take on this added responsibility.

Adolescent↗