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Biomedical subjects

E S Watson

Publications and source records attributed to E S Watson.

9 recordsLinked to original sources

The effect of marijuana smoke exposure on murine sarcoma 180 survival in Fisher rats.

Fisher rats were treated for 28 or 60 days to multiple exposures to the smoke of marijuana or marijuana placebo cigarettes. Primary, secondary and in some instances tertiary tumor implants were performed. Murine sarcoma 180 tumor cells (7.5 x 10(7)) were implanted subcutaneously on day 1, 14 and 28 following initiation of smoke exposure (28 day studies) or on day 1, 14 after cessation of smoke exposure (60 day studies). Tumor areas were measured on alternate days beginning on the second or third day after implantation for 13 or 14 days. Exposure to both marijuana and placebo smoke for 28 days (6, 9 and 18 cigarettes per day) resulted in suppressed growth of secondary and tertiary implants. Administration of delta 9 tetrahydrocannabinol (50 mg/kg, i.p., 20 days) failed to suppress the growth of primary and secondary tumors. This suggests that noncannabinoid constituents of the smoke may contribute to the suppression of tumor growth. Exposure of rats to 9, but not 4 or 6, marijuana or placebo cigarettes per day for 60 days suppressed the growth of primary but not secondary tumors. Thus, the effects of smoke exposure appear to be lost by two weeks after cessation of treatment. The possible existence of a non-cannabinoid immunostimulant in the smoke is discussed.

Animals

In vivo efficacy of antifungal oxoaporphine alkaloids in experimental disseminated candidiasis.

The efficacy of three antifungal oxoaporphine alkaloids, liriodenine, liriodenine methiodide, and oxoglaucine methiodide, was determined in a mouse model of disseminated candidiasis. Mice infected with a lethal dose of Candida albicans NIH B311 were administered varying doses of each drug intraperitoneally or intravenously 7 hr postinfection. Reductions in the number of colony-forming units (CFU) recovered per milligram of kidney tissue were observed in drug-treated animals compared to vehicle-treated control mice. Significance was determined by the Wilcoxon nonparametric rank sum test. Intravenous administration of both liriodenine and liriodenine methiodide resulted in a significant reduction in the number of recovered CFU, while there was no significant response to treatment with oxoglaucine methiodide.

Animals

The effect of subacute marijuana smoke inhalation on experimentally induced dermonecrosis by S. aureus infection.

Dermonecrosis was induced in ICR mice by subcutaneous implantation of Staphylococcus aureus absorbed onto sterile cotton pellets. This model was used to assess the effects of marijuana smoke, marijuana placebo smoke and delta 9-tetrahydrocannabinol (delta 9-THC) on the local immune response to bacterial infection. Mice were exposed to 40 or 80 "puffs" of marijuana smoke, marijuana placebo smoke or air daily for 4 consecutive days. The estimated dose of delta 9THC per day generated from 40 or 80 puffs of marijuana smoke was 3.2 and 6.4 mg/kg, respectively. A group of sentinel (Shelf) control mice were included in each experiment. The necrotic index (NI) of mice exposed to 40 or 80 puffs of marijuana smoke were 67% and 44% of control, respectively. Air exposed mice showed a necrotic index comparable to the shelf control group. In chronically (60 days) exposed mice (80 puffs per day) the necrotic index was about 12% of control, while air-exposed mice were about 40% of control. Placebo marijuana smoke exposed mice had a NI comparable to that of marijuana smoke exposed mice which suggested that the reduction in NI was unrelated to the pychomimetic component delta 9THC. To further explore which of the constituents of marijuana were responsible for the decreased NI, the ethanol extract from marijuana leaves was partioned between water (cannabinoid free) and chloroform (cannabinoid rich). Injection of the cannabinoid free fraction produced comparable decrease in the NI as observed with whole marijuana smoke, while the cannabinoid rich fraction produced no effect. delta 9THC at a dose of 10 mg/kg per day did not alter the NI.

Animals

Analogues of poison ivy urushiol. Synthesis and biological activity of disubstituted n-alkylbenzenes.

The total synthesis of different isomers and analogues of poison ivy urushiol is described. These include the positional isomers 1-5 and the nitrogen-containing analogues 6 and 8 and their mesylamino derivatives 7 and 9. 3,4-Dimethoxybenzaldehyde, m-dimethoxybenzene, resorcinol, and p-dimethoxybenzene were used as starting materials for compounds 1, 2, 3, and 4, respectively. Compound 5 is prepared by catalytic hydrogenation of bilobol isolated from Ginkgo biloba. Compounds 6 and 7 were prepared from anacardic acid as the starting material while compounds 8 and 9 were prepared from phenol as the starting material. Compounds 1-9 were tested for their ability to cross-react with poison ivy urushiol in sensitized guinea pigs. Compounds 6 and 8 were reactive at the 10-microgram dose level when applied topically, while compound 1 was a skin irritant at that dose. On the other hand, compounds 2-5, 7, and 9 showed no cross-reactivity up to the 30-micrograms dose level. Structural requirements for cross allergenicity are discussed.

Animals

Cutaneous irritation in the topical application of 30 antineoplastic agents to New Zealand white rabbits.

Of 30 antineoplastic agents studied for their primary irritation potential in rabbits, 9 showed some potential for irritation. Five of these 9 agents produced a significant dermal irritation. None of the irritation observed was considered to be irreversible skin damage. The study further showed a strong correlation between irritation observed by the Draize method and acute inflammation evaluated histopathologically. There was a tendency toward increased epidermal thickness of irritated skin sites. None of the agents produced gross or microscopically visible lesions in the internal organs observed.

Administration, Topical

Conformational aspects of the antifibrillatory activity of procaine.

The effects of procaine and four semi-rigid conformational analogs (compounds 1,2,3 and 4) were tested and compared on isolated rabbit atria. Procaine and the four analogs produced positive inotropic effects at all dose levels tested. The antifibrillatory activity of procaine and its analogs arranged in decreasing order of activity was compound 4 greater than 3 greater than 2 greater than 1 greater than procaine. The antifibrillatory activity of the compounds correlated to the distance between the ring nitrogen and the ester oxygen; that is, as the N-O distance increased the concentration required to reduce the following frequency decreased. However, the compound became more toxic as the N-O distance increased. Our data do not confirm the commonly regarded direct relationship between local anesthetic activity and antifibrillatory activity of procaine. Differences in activity displayed by the isomers of procaine could reflect differences in the ability of these analogs to bind to receptors responsible for the respective actions.

Animals

Spectrophotometric evaluation of carboxyhemoglobin in blood of mice after exposure to marijuana or tobacco smoke in a modified Walton horizontal smoke exposure machine.

Carboxyhemoglobin (COHb) values were determined in mice exposed to varying amounts of marijuana and tobacco cigarette smoke utilizing a spectrophotometric technique. Mice were exposed to smoke inhalation in a modified Walton horizontal smoke exposure machine, whereby rodents can be exposed to multiples of 1-min smoke exposure cycles. Smoke exposure was intermittent; during the first 30 sec of each 1-min cycle, the subjects were exposed to smoke diluted either 1:10 or 1:5 with air. During the second half of the cycle the animals were given fresh air. There was a positive linear relationship between COHb values obtained and the number of puffs of marijuana smoke administered via either 2, 4, 6, or 8 "puffs" of marijuana smoke. COHb levels in plasma did not increase in animals given multiple 8-puff episodes of smoke daily as long as a 60-min period was interposed between smoking episodes. COHb values in mice exposed to tobacco smoke were significantly higher than those in mice receiving equal numbers of exposures to marijuana smoke. Mean COHb values of mice receiving 8 consecutive puffs of marijuana smoke were 18.6 and 22.0% saturation, but CO was rapidly cleared from the blood. This rapid clearance suggests that the binding affinity of CO for mouse hemoglobin may be be weaker than that of human hemoglobin. Mice similarly exposed to 6 or 8 puffs of tobacco smoke had mean COHb values of 24.6 and 28.5% saturation, respectively. No acute lethal effects were observed in mice receiving multiple daily episodes of 8 puffs per episode of marijuana smoke, whereas mice exposed to a single 8-puff episode of tobacco smoke suffered about 50% acute lethal effects.

Animals