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Biomedical subjects

G M Smith

Publications and source records attributed to G M Smith.

At least 235 records · Page 13Linked to original sources
PubMed1978

Toward the development of a potent, nonsedating, oral analgesic.

The separate and combined analgesic effects of 10 mg of oral amphetamine sulfate and 25 mg of oral anileridine dihydrochloride were studied in 24 healthy, adult, male volunteers. Tolerance of progressively increasing pain produced by the Submaximum Effort Tourniquet Technique was tested four times in each subject: after amphetamine, after anileridine, after the combination, and after a matching placebo. Treatments were administered double blind and in counterbalanced order. Elapsed time to report of slight, moderately distressing, very distressing, and unbearable pain was recorded on each trial. The four oral treatments differed significantly for very distressing and for unbearable pain. At each of the three upper pain levels, the mean tolerance times for anileridine and amphetamine were similar; each was longer than placebo but shorter than the combination; and the effect of the combination was approximately the sum of the effects of the two components.

Administration, Oral↗
PubMed1978

Effect of phosphate buffer concentration on the heat resistance of Bacillus stearothermophilus spores suspended in parenteral solutions.

The effect of various quantities of Butterfield phosphate buffer added to four parenteral solutions on the survival of Bacillus stearothermophilus spores heated at 121 degrees C was determined. The effect of the addition of phosphate buffer on spore survival varied with the parenteral solution. Spore survival was increased or decreased, depending upon the composition of the parenteral solution and the buffer concentration. The results obtained in these experiments attest to the fact that environmental factors, including the type of ions present and ionic concentration, affect the heat destruction rate of B. stearothermophilus spores. Therefore, the sterilization requirements of a product such as a parenteral solution may be affected by small changes in formulation.

Buffers↗
PubMed1977

Intragastric titration of acid in the perfused rat stomach preparation following parenteral and intraluminal stimulation.

The anaesthetised rat stomach preparation was adapted to assay intraluminally administered stimulants and inhibitors of acid secretion by continuously recirculating the perfusate (15 ml of 5% glucose) and measuring acid by the pH-stat technique. The responses obtained were linear. Continuous artificial neutralisation of the stomach to pH 5.5 as well as variation of the pH between 6.5 and 4.0 did not significantly alter the sensitivity of the preparation to intravenously administered human gastrin-heptadecapeptide I (HG I). Basal acid secretion however significantly declined following stepwise lowering of the intragastric pH between 6.5 and 4.0. The threshold values for responses to i.v. HG I were below 16 ng. 6 doses could be given per rat without tachyphylaxis. Acetylcholine, 1.3, 2.5, 5.2 and 10.4 micron g/ml in the perfusate, induced a dose-dependent linear (r=0.902) acid secretion. Metiamide 1.66 mg/ml in the perfusate, produced a parallel shift to the right of the HG I dose--response curve producing an agonist dose ratio of 3.66. The data suggest that intragastrically applied stimulants and inhibitors of acid secretion can be studied precisely in this relatively simple preparation.

Acetylcholine↗
PubMed1977

The effect of intravenous adenosine diphosphate on the number of circulating platelets in experimental animals: inhibition by prostaglandin E1, dipyridamole, SH-869 and VK-774.

The number of circulating platelets was monitored in anaesthetized animals by a continuous flow technique, using a Technicon Autocounter. Intravenous infusions of adenosine diphosphate (ADP) produced transient, dose-dependent falls in circulating platelet numbers in rabbits, dogs, rats, pigs and squirrel monkeys. The rat was the most sensitive of the species investigated. In the rabbit, the effect of a submaximal dose of ADP was inhibited in a dose-dependent manner by intravenous infusions of prostaglandin E1 (PGE1), dipyridamole, and two derivatives of dipyridamole (SH-869 and VK-774). The dose-response curves for PGE1, SH-869 and VK-774 were approximately parallel, whereas that for dipyridamole was considerably less steep. PGE1 was the most potent inhibitor, but the duration of action was very short. Dipyridamole and SH-869 produced inhibition of long duration. The duration of action of VK-774 was intermediate. All inhibitors produced marked and often long-lasting hypotension. The fact no inhibition of ADP effects could be demonstrated with dibenzyline and hexamethonium, which also produced marked hypotension of long duration, indicated that inhibition of the ADP effect by the four antagonists studied was not due to changes in blood pressure.

Adenosine Diphosphate↗
PubMed1977

C-type and intracisternal A-type virus particles during epidermal carcinogenesis by tobacco smoke condensate in BALB/c mice.

Electron microscopic observations of sequential stages of skin carcinogenesis induced by tobacco smoke condensate (SC) and a cyclohexane fraction of tobacco smoke condensate (G) revealed an increase in incidence of intracisternal A particles within the epidermal cells. Tumours induced by SC also contained C-type particles, but these were not seen in G-induced tumours or after irritant or solvent treatment. There was no evidence of an increase in intracisternal A particles after irritant or solvent treatment. A direct relationship between the proliferation of A particles and neoplastic growth of BALB/c mouse epidermis appears likely. The data suggest possible activation of a latent C-type virus by SC.

Animals↗
PubMed1977

High-resolution autoradiographic localization of 3-methylcholanthrene-3H in the skin of Balb/c mice after topical application.

Tritiated 3-methylcholanthrene (MC) was traced by electron microscope autoradiography in Balb/c mouse epidermis 24 h after topical application in vivo. Quantification of the autoradiographs indicated that the distribution of radioactivity was non-random. The frequency of silver grains was similar in both nuclei and cytoplasm of epidermal cells. A concentration of labelling was detected in association with nuclear and cell membranes but to a greater degree with the dermo-epidermal junction. Results are consistent with previous work on the binding of hydrocarbons to soluble proteins and nucleic acids. The significance of the association of radioactivity with the dermo-epidermal junction is discussed.

Administration, Topical↗
PubMed1976

The development of a reliable and sensitive bioassay for gastrin in body fluids.

The sensitivity and reliability of the Ghosh and Schild rat stomach preparation was improved by implantation of bulky intragastric cannulae, recirculation of the perfusate and measurement of conductivity instead of pH. With these procedures, the threshold values for gastrin I were in the range of 1-2 ng. In attempts to increase the sensitivity further it was shown that neither vagotomy nor antrectomy influenced the sensitivity of the method. The threshold values were not lowered by attempts to reduce gastrin metabolism through nephroligature or small bowel resection. Although rats fitted with portacaval shunts did raise the threshold, the limited increase in sensitivity was also achieved by selecting the rats that gave an initially high response to a test dose of gastrin thus avoiding the complicated shunt operation. The assay procedure enabled statistically valid measurements of gastrin in plasma and from tumour extracts from patients suffering from the Zollinger-Ellison Syndrome to be assayed using a 2 + 2 block design.

Analysis of Variance↗
PubMed1976

Effect of storage time and temperature and the variation among replicate tests (on different days) on the performance of spore disks and strips.

Laboratory-prepared spore disks were stored for 96 weeks at 22 degrees C with 50% relative humidity (RH) and at 4 degrees C with less than 1% RH. At the same time commercial spore strips were stored for 64 weeks at 22 degrees C with 50% RH. The spore count per unit and the heat resistance were measured at the beginning of the experiment and after 16, 32, 48, 64, 80, and 96 weeks of storage. The laboratory-prepared spore disks stored at 4 degrees C with less than 1% RH showed less change in numbers of spores per disks and decrease in the survival time than did the disks stored at 22 degrees C with 50% RH. Both the laboratory-prepared spore disks and the commercial spore strips stored at 22 degrees C with 50% RH decreased in survival times with increased storage time. The relative change in the survival times with storage was less for the commercial spore strips than for the laboratory-prepared spore disks.

Drug Resistance, Microbial↗
PubMed1975

Increase in type A virus particles induced in BALB/c mouse epidermis during chemical carcinogenesis.

Electron microscopic observations of normal BALB/c mouse epidermis revealed the presence of isolated intracisternal A particles. Hyperplasia, papilloma and carcinoma formation induced by topical application of the carcinogenic polycyclic hydrocarbons benz(a)pyrene (B(a)P) and 3-methylcholanthrene (MC) is accompanied by an increase in the mumber of A particles. Topical application of a non-carcinogenic irritant alpha-pinene (alpha P) failed to provide comparable changes. Examination of the nuclei indicated occasional electron dense granules in the nucleoplasm which became more common throughout the progression of carcinogenesis.

Animals↗
PubMed1975

Mechanism of methylxanthine sensitization of norepinephrine responses in a coronaryartery.

Beta-adrenergic receptor-mediated relazation to norepinephrine was enhanced by caffeine amd aminophylline in a coronary artery preparation of the beef in vitro. Augmented responses were not obtainable in the presence of known inhibitors of the extraneuronal uptake and metabolism of norepinephrine, estradiol-17beta, and the haloalkylamine GD-131, which themselves potentiate responses. In addition, the effect on the norepinephrine dose-response curve of the combination of a methyixanthine and U-0521,the latter a potent inhibitor of catechol O-methyltransferase, the major enzyme of catecholamine inactivation in vascular tissue, did not differ from that of U-0521 alone. Studies of the extraneuronal accumulation of '3H-labeled norepinephrine revealed that caffeine and aminophylline, along with the known inhibitors, materially reduced theaccumulation of label in coronary tissue. It is concluded that the methylxanthinesenhance beta-adrenergic receptor-mediated responses via a blockade of catecholamine uptake, giving rise to an increased concentration of agonist at receptors, and not by an action linked to cyclic AMP accumulation, consequent to receptor activation.

Aminophylline↗
PubMed1975

Peter's anomaly.

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Corneal Opacity↗