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S M Strain

Publications and source records attributed to S M Strain.

7 recordsLinked to original sources
PubMed1992

Morphine differentially affects domoic acid and kainic acid toxicity in vivo.

The effect of systemic injections of morphine on behavioural toxicity and hippocampal (CA3 region) damage produced by both domoic and kainic acids was investigated in mice. Low doses of morphine (2.0 and 4.0 mg kg-1), but not higher doses, significantly antagonized the toxic response to a previously determined TD50 of domoic acid. By contrast, low doses of morphine had either minimal or no effect on the response to an equitoxic dose of kainic acid (TD50), but higher doses (6.0 and 8.0 mg kg-1) resulted in significant potentiation of kainate toxicity. These results provide the first evidence of a pharmacological dissociation between the mechanisms of domoic acid and kainic acid toxicity in vivo, suggesting that these two toxins produce behavioural and hippocampal toxicity via overlapping but non-identical mechanisms.

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PubMed1991

Hippocampal damage produced by systemic injections of domoic acid in mice.

The effect of systemic administration of domoic acid, a potent structural analogue of kainic acid, on the mouse hippocampus has been studied using light and electron microscopic techniques. Intraperitoneal injections of either domoic acid (4 mg/kg) or kainic acid (32 mg/kg) produced a series of behavioural changes including sedation, rigidity, stereotypy (scratching, head nodding), balance loss, and discrete or generalized convulsions. Both qualitative and quantitative histological analysis revealed similar but not identical patterns of neuronal damage in the hippocampal formation of domoic acid- and kainic acid-treated mice. With both toxins the most extensive damage was always observed in the CA3 region of the hippocampus, with lesser degrees of damage observed in other hippocampal regions (CA4 greater than CA1 greater than CA2 greater than dentate granule cells). In general, neuronal damage was more widespread following administration of kainic acid than domoic acid. In the CA3 region, however, the percentage of cells exhibiting damage was greater following domoic acid (82.1%) than kainic acid (58.8%) following systemic administration. No damage was found in the hippocampi of vehicle control-treated mice. Electron microscopy of the CA3 region following domoic acid revealed two subpopulations of damaged neurons: (1) swollen cells that exhibited vacuolization of their cytoplasm and (2) shrunken irregularly shaped electron-dense cells. Swollen processes of astroglial origin were observed surrounding electron-dense cells, and electron-dense processes were often found extending into the neuropil. These results suggest that although domoic acid and kainic acid produce similar changes in both open field behaviour and hippocampal neuropathology, responses to these toxins are not identical at equitoxic doses. Lesions in the domoic acid-treated mice are more selective for the CA3 hippocampal region than are those produced by kainic acid following systemic administration. Domoic acid may, therefore, be a better tool for studying certain aspects of excitatory amino acid neurotoxicity.

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PubMed1991

Pharmacology of systemically administered domoic acid in mice.

Domoic acid, a structural analogue of kainic acid, has been identified as the toxin that poisoned people who consumed contaminated blue mussels harvested from eastern Prince Edward Island in December of 1987. To investigate the pharmacology of domoic acid in vivo we injected groups of mice with serial dilutions of extracts of contaminated mussels and verified domoic acid concentrations using high performance liquid chromatography. Mice progressed through a series of behavioural changes that were both reproducible and dose-dependent. These behaviours formed the basis of a rating scale that was used to reliably quantitate domoic acid concentrations as low as 20 micrograms/mL. This scale was then used to compare the relative toxicity of domoic acid contained in four formulations: namely, (1) extracts of contaminated mussels, (2) pure domoic acid, (3) extracts of noncontaminated mussels that were "spiked" with pure domoate, and (4) extracts of the algal source of domoic acid. Interpolation of the resulting dose-response curves produced median toxic dose (TD50) values of 2.9, 3.9, 4.9, and 4.2 mg/kg for the four formulations, respectively. Statistical analysis of these data revealed that curves for all formulations of domoic acid were parallel, but that extracts of contaminated mussels were significantly more potent than any of the other formulations at low and intermediate doses of domoic acid. We further compared domoic acid toxicity with that produced by kainic acid. Dose-response curves for both compounds were statistically parallel and both toxins were equally efficacious. The TD50 values were 3.9 and 31.9 mg/kg for pure domoic acid and kainic acid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Direct vagal input to neurons in the area postrema which project to the parabrachial nucleus: an electron microscopic-HRP study in the cat.

This study in cat examines the synaptic relationship of vagal afferents to parabrachial projecting neurons in the area postrema (AP) using anterograde and retrograde transport of horseradish peroxidase (HRP). Wheat germ agglutinin-HRP injected into the parabrachial nucleus (PBN) produced retrograde neuronal labeling in the AP and in the nucleus of the tractus solitarius bilaterally, but with an ipsilateral predominance. Labeled neurons were confined mainly to the caudal 2/3's of the AP. Following injection of WGA-HRP into the PBN and HRP into the nodose ganglion in the same animal, examination of sections of the AP with the electron microscope revealed anterogradely labeled axon terminals in apposition to retrogradely labeled somata and dendrites. In some instances, labeled terminals were observed to form synaptic contacts with retrogradely labeled neurons. We conclude that in the cat a vagal input to neurons in the AP is monosynaptically relayed to the PBN.

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PubMed1976

Immunotherapy with nonviable microbial components.

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

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PubMed1975

Tumor regression caused by endotoxins and mycobacterial fractions.

A transplantable hepatocarcinoma of guinea pigs was used as an experimental model for immunotherapy of cancer. Earlier work showed that complete regression of 6- to 7-day-old tumors could be obtained in about 60% of cases by inoculation of the tumors with live BCG or certain fractions of BCG attached to minute oil droplets and suspended in Tween-saline. One of the most essential fractions was P3, a nonsensitizing, nonantigenic trehalose mycolate related to, but not identical with, cord factor. We now report that oil-droplet preparations containing P3 and bacterial endotoxin (ET) produced cure rates of up to 90% in the same system. In addition, regression was faster than with BCG, and older tumors could be treated successfully. The most effective ET's were from rough strains of salmonellae, known as Re mutants, which could not synthesize and attach the polysaccharide portion of endotoxin.

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