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Biomedical subjects

M G Simpson

Publications and source records attributed to M G Simpson.

16 recordsLinked to original sources

Mechanism of action of triethyltin on identified leech neurons.

The effects of triethyltin (TET) have been examined using intracellular electrophysiological recording techniques from identified neurons of the leech (Hirudo medicinalis) CNS and from salivary glands of the giant Amazon leech (Haementeria ghilianii). TET, at concentrations as low as 10(-5) M, caused a reversible neuronal membrane depolarisation accompanied by an increase in firing frequency of action potentials (which could lead to conduction block at 10(-4) M) and a concomitant decrease in membrane resistance. TET-induced membrane depolarisation still occurred in saline where Na+, K+ and Ca2+ had been replaced by choline. TET decreased the rate of the depolarising and repolarising phases of the action potential. This also occurred in Haementeria salivary gland cells, in which the only inward cation channel is a calcium channel. The calcium channel blocker, manganese, did not block the effects of TET. TET counteracted the effects on the action potential of the potassium channel blocker, tetraethylammonium chloride (TEA). TET-induced neurotoxicity occurred independently of any resultant toxic effects on the myelin sheath. The action of TET is consistent with our view that it causes an increase of intracellular free Ca2+ probably via release from intracellular stores and inhibition of Ca2+ reuptake. A resulting inhibition of the Na+/K+ and Ca2+ pumps may also occur.

Action Potentials

Alpha 2U-globulin: measurement in rat kidney and relationship to hyaline droplets.

The concentration of renal alpha 2U-globulin increased in a dose-dependent manner in adult male but not female rats which received a single dose of 2,2,4-trimethylpentane (TMP). After administration of a single dose of 12 mmol TMP/kg to adult male rats, the renal concentration of alpha 2U-globulin reached a peak at 48 hours and returned to near background level after 7 days. These changes in renal alpha 2U-globulin concentration were closely paralleled by changes in renal hyaline droplet formation. Renal alpha 2U-globulin and hyaline droplets were absent in normal pre-puberty male rats, and neither could be stimulated by a single dose of TMP. alpha 2U-Globulin was localised in the renal cortex of adult male rats, in particular the S2 segment of the proximal tubule. A greater staining intensity due to alpha 2U-globulin was seen in the S2 and adjacent segments after a single dose of TMP. A strong association is suggested between the presence of renal hyaline droplets and the occurrence of alpha 2U-globulin.

Alpha-Globulins

Alpha 2U-globulin: measurement in rat kidney following administration of 2,2,4-trimethylpentane.

Hyaline droplet formation was stimulated markedly in the kidneys of post-puberty male rats 24-48 h after a single oral dose of 12/24 mmol/kg 2,2,4-trimethylpentane [TMP]. Renal hyaline droplet formation could not be detected in female rats or in pre-puberty male rats following similar doses of TMP. A dose-dependent increase in the renal concentration of the androgen-dependent low molecular weight protein, alpha 2U-globulin was observed in post-puberty male rats 24 h after a single oral dose of TMP, over the range 0.3-12.0 mmol/kg. After administration of a single dose of 12 mmol/kg TMP to male rats, the renal concentration of alpha 2U-globulin rose steadily up to a peak after 48 h and then returned slowly to near normal after 7 days. Renal alpha 2U-globulin could not be detected in female rats and in pre-puberty male rats. An immunocytochemical assay was developed to examine the distribution of alpha 2U-globulin within the kidney. alpha 2U-Globulin was localised primarily in the S2 segment of renal proximal tubules in untreated male rats. Rats which received a single dose of 12 mmol TMP/kg showed not only a greater staining intensity, due to the presence of a higher concentration of alpha 2U-globulin, but also staining in adjacent segments of the renal cortex. Several urinary biochemical indicators of nephrotoxicity were measured daily in male rats for up to 72 h following a single dose of 12 mmol TMP/kg. Renal proximal tubular function was unimpaired by TMP treatment. On the basis of studies in untreated and TMP-treated rats, a strong association has been found between the presence of renal hyaline droplets and the occurrence of renal alpha 2U-globulin. The findings in the present study provide an explanation for the occurrence of renal hyaline droplets only in adult male rats, but do not, as yet, establish the toxicological significance of increases in renal hyaline droplet formation.

Alpha-Globulins

Incorporation of radioactive precursors into filarial larvae of Brugia developing in susceptible and refractory mosquitoes.

The incorporation of tritiated precursors injected into mosquito hosts parasitized by developing filarial larvae of Brugia patei has been studied by autoradiography in 2 species of mosquito, Aedes togoi in which filarial development was normal and Anopheles labranchiae atroparvus in which filarial development was abnormal. In both mosquito hosts there was significant incorporation into 4--5-day-old developing larvae of uridine and amino acids (isoleucine, leucine, valine, arginine, lysine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, and proline), although lower incorporation of methionine, tyrosine, and tryptophan was found during abnormal development. No incorporation of thymidine, hydroxytryptophan, dopa, or carbohydrate was found at this stage of larval development. Some incorporation of glucose and dopa was found in or around earlier stages of development in An. l. atroparvus. Mosquito flight muscle showed lower incorporation of glucose, but not of amino acids, around the site of filarial parasite development. The flight muscle of An. l. atroparvus showed a higher level of incorporation of lysine compared to that in A. togoi and higher levels of lysine and valine were found in the abnormally developing filarial larvae in the refractory mosquito.

Aedes

Micro-organisms in filarial larvae (Nematoda).

Unusual bodies have been described in the hypodermal tissues of larval Dirofilaria immitis and Brugia pahangi. Ultrastructural evidence indicates that these bodies are probably Gram-negative micro-organisms. It appears that the presence of large numbers of these bodies in an early embryo may affect development adversely. Their importance at later stages of development of filariae is not known.

Animals

Effect of IDPN on the expression of POMC-derived peptides in rat motoneurones.

Immunocytochemistry was used to detect beta-endorphin and alpha-melanotropin (alpha-MSH) in lumbar spinal motoneurones in rats treated with beta,beta'-iminodiproprionitrile (IDPN), a neurotoxicant that targets motoneurones or corn oil, which has no known neurotoxicity. After IDPN treatment most of the motoneurones were immunoreactive for both peptides but after corn oil treatment immunostaining was negligible. It is suggested that increased expression of the POMC-derived peptides may be part of the regenerative repertoire of the damaged motoneurone regardless of the cause of the lesion. Alternatively the peptides may simply accumulate in the motoneurones as a result of impaired axoplasmic transport.

Animals