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Biomedical subjects

C J Carter

Publications and source records attributed to C J Carter.

At least 109 records · Page 6Linked to original sources
PubMed1979

Decreased platelet thrombogenecity in association with increased platelet turnover and vascular damage.

Platelet turnover is increased when platelets interact with prosthetic surfaces and damaged vessel wall. To determine whether the resulting increase in young platelets is associated with an increased tendency to thrombosis, we induced a state of increased platelet turnover in rabbits by inserting a sterile cannula into the abdominal aorta and tested for platelet thrombogenecity by measuring the deposition of circulating platelets onto a second injury site in the carotid arteries. Platelet half-life was decreased and platelet turnover was increased after the aortic cannulation, although the circulating platelet count remained unchanged. Platelet thrombogenecity determined 20 hr after cannulation was significantly decreased when compared to sham-operated animals. Ear bleeding studies demonstrated that the platelets circulating in cannulated animals were hemostatically less effective than those in sham-operated animals. This effect was intrinsic to the platelet and was associated with a platelet function defect. These data suggest that platelets exposed to a damaged or foreign surface interact with the surface and then circulate in a less reactive state.

Animals↗
PubMed1978

A study of the sites of interaction between dopamine and 5-hydroxytryptamine for the production of fluphenazine-induced catalepsy.

The effect of reducing 5-hydroxytryptamine (5-HT) concentration within various areas of the central dopamine (DA) system on catalepsy has been investigated. The neurotoxin 5,7-dihydroxytryptamine was used to selectively deplete 5-HT in the striatum, nucleus accumbens septi, tuberculum olfactorium or substantia nigra. Localised depletion of 5-HT within the nucleus accumbens septi and substantia nigra reduced the cataleptic effects of the neuroleptic agent fluphenazine, while lesions of the striatum or tuberculum olfactorium were without effect. Each injection of neurotoxin resulted in a 38--47% depletion of 5-HT in the target site: DA levels were not significantly altered. The results suggest that varied dopamine/5-hydroxytryptamine interactions within the nucleus accumbens may contribute to the action of the neuroleptic. The reduction of fluphenazine-induced catalepsy produced by 5-HT depletion within the substantia nigra supports the concept of a controlling influence of 5-HT on nigro-striatal DA function.

Animals↗
PubMed1978

Thrombogenic effect of high-dose aspirin in rabbits. Relationship to inhibition of vessel wall synthesis of prostaglandin I2-like activity.

Aspirin is a promising antithrombogenic agent. It inhibits the generation of thromboxane A(2) by acetylating platelet cyclo-oxygenase. Aspirin also inhibits vessel wall production of PGI(2) which is an inhibitor of platelet aggregation, and therefore is potentially thrombotic. To investigate these two opposing effects we studied the effects of aspirin upon fibrin accretion onto experimentally induced venous thrombi in rabbits and on the PGI(2)-like activity of vessel wall using the thrombin-induced [(14)C]serotonin release assay. A 200-mg/kg dose of aspirin significantly augmented thrombus size when compared to (a) sodium salicylate administered in equal doses, (b) aspirin in a 10-mg/kg dose or (c) controls (P < 0.001). A 200-mg/kg dose of aspirin totally inhibited vessel wall PGI(2)-like activity whereas aspirin in a 10-mg/kg dose produced less inhibition, and 200 mg/kg sodium salicylate had no effect. Local instillation of tranylcypromine, an inhibitor of PGI(2) formation, also significantly augmented thrombus size compared to saline-treated controls and totally inhibited the production of PGI(2)-like activity. The thrombogenic effect of high dose aspirin was lost if an interval of 2.5 h or longer elapsed between vessel damage and drug administration, indicating that in contrast to the platelet, the effect of aspirin on vessel wall prostaglandin synthesis is relatively short-lived. It is concluded that aspirin, in doses higher than those used clinically, can augment experimental thrombosis, presumably by inhibiting the synthesis of vessel wall PGI(2).

Animals↗
PubMed1978

Sex differences in the antithrombotic effects of aspirin.

Aspirin inhibits platelet function by acetylating platelet cyclooxygenase. Recent clinical trials indicate that aspirin is a promising antithrombotic agent against both venous and arterial thrombosis, but somewhat surprisingly this protective effect appears to be limited to males. To examine the potential sex-related differences in response to aspirin, we developed an animal model for quantitating fibrin accretion into an injury-induced thrombus and used it to study the effects of aspirin on thrombus size in male and female rabbits. Platelet prostaglandin synthesis was estimated by assay of platelet malondialdehyde and was significantly decreased in both male and female rabbits following treatment with 10 mg/kg aspirin (p less than 0.001). This inhibitory effect was not different for platelets from male and female rabbits. Thrombus size was significantly decreased in aspirin-treated male rabbits when compared to controls (p less than 0.05), but this aspirin effect was not apparent in female rabbits or rabbits of either sex treated with 10 mg/kg sodium salicylate. These findings support the results of clinical trials that were obtained by retrospective subgroup analysis. The reason for the sex difference is not known, but the findings raise an important issue in relationship to this mechanism of the antithrombotic effect of aspirin.

Animals↗
PubMed1977

Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes.

1. The inhibitory actions of ten trichothecene antibiotics were investigated, in reticulocyte cell-free systems synthesizing protein in vitro, by studying polyribosome profiles and kinetics of amino acid incorporation in the presence or absence of the drugs. 2. The modes of action observed were critically dependent on the drug concentrations used, but the antibiotics tested could be divided into four distinct groups, each exerting a characteristic inhibitory response. 3. The inhibitory action observed in every case was controlled by the chemical structure of the individual trichothecene and in particular was closely related to the nature of the substituent groups present on C-3, C-4, C-8 and C-15 of the molecule.

Animals↗
PubMed1976

Prevention, by ribosome-bound nascent polyphenylalanine chains, of the functional interaction of t-2 toxin with its receptor site.

1. The inhibitory effects of T-2 toxin and trichodermin on poly(U)-directed polyphenylalanine synthesis were studied by using cell-free systems from reticulocytes. Conditions for amino acid incorporation were carefully chosen in an attempt to ensure that the large majority of poly(U) chains bound only one ribosome engaged in protein synthesis and that all such ribosomes carried nascent polyphenylalanine chains containing approximately the same number of residues. 2. Cell-free systems were allowd to synthesize polyphenylalanine, and T-2 toxin and trichodermin were added to the incorporation mixtures at various times. Irrespective of the time of addition, trichodermin (50 mug/ml) inhibited polyphenylalanine synthesis by approx. 70%. In contrast, although T-2 toxin (40 mug/ml), when added at early incubation times, could inhibit polyphenylalanine synthesis with a maximum of 50%, the drug had no effect on the system when added after a critical time-period. 3. It is concluded that although both T-2 toxin and trichodermin can inhibit peptide-bond formation on ribosomes at the level of the peptidyl transferase catalytic centre the presence, on ribosomes, of nascent polyphenylalanine chains above a certain critical chain length excludes T-2 toxin from functional interaction with its receptor site.

Animals↗
PubMed1976

Inhibition of protein synthesis in reticulocyte lysates by trichodermin.

1. The effect of trichodermin as an inhibitor of eukaryotic protein synthesis was studied in a reticulocyte cell-free system. 2. Trichodermin at a concentration of 25 mug/ml inhibits total protein synthesis instantaneously and stabilizes polyribosome profiles. Conversely, at a concentration of 0.25 mug/ml the drug inhibits total protein synthesis by only 70-75% and allows 30-35% breakdown of the polyribosomes in the system. These effects were compared with those produced by two other drugs (pactamycin and anisomycin) examined under conditions identical with those used for trichodermin.

Animals↗
PubMed1976

The toxicity of brominated sesame oil and brominated soybean oil in miniature swine.

Miniature swine were fed brominated sesame oil at dietary levels of 0, 5, 25, 50 or 500 mg/kg of body weight for 17 weeks and brominated soybean oil at levels of 0, 5, 50 or 500 mg/kg of body weight for 28 weeks. Growth rate and food intake were decreased only at the high dose level in the brominated sesame oil study. In both studies, signs of lethargy and ataxia occurred in pigs fed the highest dose, and were probably due to a dose-related increase in serum bromine concentrations. Marked elevations in lactic dehydrogenase (LDH), serum glutamic-oxalacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) values were seen at the highest dose level with both substances and these enzyme activities were increased at the 50 mg/kg dose level in the brominated sesame oil study. Histopathologic lesions were confined to animals given the highest dose level of either oil. Marked fatty degeneration of the hepatic plate cells and renal tubular epithelial cells were seen in both studies. In the brominated sesame oil study, neutral fat was moderately increased in the myocardium of the pigs fed 500 mg/kg. However, marked diffuse accumulation of LDH, marked diffuse fatty degeneration and focal degeneration, and/or necrosis of individual or small groups of cardiac muscle fibers were seen in the group fed brominated soybean oil at 500 mg/kg. A moderate to marked testicular atrophy was also observed in this group. A dose-related accumulation of total and hexane-soluble bromine was observed in all tissues examined in both studies; the highest concentrations occurred in adipose tissue of the pigs given the highest dose level. Kidneys, livers, hearts and thyroids of these groups also contained large amounts of bromine. In pigs given the 50 mg/kg dose level, total and hexane-soluble bromine concentrations were higher in the brominated sesame oil study than in the longer brominated soybean oil study and may be responsible for the elevations in LDH, SGPT and SGOT activities in this group.

Animals↗