Many strokes are thought to develop as a consequence of platelet aggregation on areas of arterial endothelial damage, with subsequent embolism or thrombus formation. Aspirin prevents platelet adhesion and aggregation by inhibiting the formation of thromboxane A2 by platelets. This suggests that aspirin could be used to prevent stroke. However aspirin also inhibits endothelial formation of the anti-aggregatory substance prostacyclin, though probably only in a slightly higher dose than that just capable of inhibiting platelet aggregation. Consequently, too high an aspirin dose may defeat its purpose. The effect of aspirin on platelets lasts for as long as they survive, whereas the effects of aspirin on endothelium are shorter. Theoretical considerations suggest that aspirin, given in brief pulses just to reach platelet inhibitory concentrations in plasma, and administered at the maximum interval that will maintain inhibition of platelet aggregation, should offer the most favourable balance between altered platelet and altered endothelial function from the viewpoint of stroke prevention. Data are presented showing that rapid rather than slow or delayed release aspirin preparations are necessary to achieve suitable plasma aspirin concentration-time profiles in humans, and that a peak plasma aspirin concentration of around 1.2 mg/L is necessary in vivo to inhibit aggregability of previously untreated platelets.

Aspirin↗

PubMed1986

Peripheral venous plasma aspirin concentrations and platelet aggregation inhibition produced by enteric-coated aspirin formulations.

In a random cross-over design, six healthy consenting adult volunteers were given on separate occasions single doses of 300-650 mg of 3 different formulations of enteric-coated aspirin. Over various intervals for 48-54 h following dosage, plasma aspirin and salicylate concentrations were measured together with percentage inhibition of platelet aggregation activated by threshold concentrations of sodium arachidonate alone and combined with ADP and collagen. In all subjects each formulation delivered measurable quantities of aspirin to the peripheral circulation, the unchanged drug being detected at various times up to and including 28 h after dosage. Moreover, low aspirin concentrations were found to co-exist with unimpaired platelet aggregation. All 3 formulations yielded statistically significant (P less than 0.01) inhibition of platelet aggregation activated both by arachidonate and by the combination of aggregants when tested 24-29 and 48-54 h after dosage; there were no significant differences (P greater than 0.05) between the 3 formulations in this regard. Two different patterns of delivery of unchanged aspirin to the systemic circulation from these enteric-coated formulations were apparent. These patterns may be important when considering which aspirin formulation might be most appropriate in chronic use for an antiplatelet effect. None of the enteric-coated formulations used in this study may be optimal in this regard.

Adenosine Diphosphate↗

PubMed1986

A new formulation of aspirin: bioavailability and analgesic efficacy in migraine attacks.

Plasma aspirin and salicylate concentrations were followed after 600 mg of a new palatable glycinated preparation of aspirin was given to six healthy male volunteers in an attempt to investigate whether pre-gastric absorption of aspirin could occur. In each subject the drug was administered by three different routes, viz. (i) swallowed with water, (ii) dissolved sublingually and retained in the mouth, and (iii) allowed to disperse on the tongue, and then swallowed without water intake. Using the latter route of administration and the same aspirin formulation, plasma aspirin and salicylate concentrations were also followed in 10 patients during acute migraine attacks. These results were compared with those from another 10 migraineurs given 600 mg of soluble aspirin swallowed with water during attacks. Aspirin and salicylate pharmacokinetic parameters (Cmax, tmax, t1/2, Kabs and AUC) in the normal volunteers were not significantly different (p greater than 0.05) whether glycinated aspirin was swallowed with water or swallowed without water after dispersion in the mouth. However, negligible aspirin was absorbed when the glycinated preparation was retained in the mouth. In migraine patients, there was no significant difference (p greater than 0.05) between the bioavailabilities of soluble aspirin swallowed with water (AUC = 5.7 +/- 2.3 mg h/l) and glycinated aspirin swallowed without water (AUC = 4.4 +/- 1.6 mg h/l). There also was no significant difference (p greater than 0.05) when the time courses of pain relief were compared, both treatments being associated with a significant (p less than 0.01) analgesic effect. The glycinated aspirin was thus bioequivalent to swallowed aspirin but has no advantages for migraineurs over soluble aspirin if water is readily available for self-administration.

Administration, Oral↗

PubMed1985

Psychiatric complications associated with geriatric surgery.

Detection of pre-existing psychopathologic problems in the geriatric surgical patient can often preclude further psychiatric complications. When complications such as delirium arise, collaboration between the surgeon and the psychiatrist enhances a satisfactory outcome.

Aged↗

PubMed1976

Effects of continuous light and darkness on the eyes of the troglobitic salamander Typhlotriton spelaeus.

Larval Typhlotriton spelaeus collected from five caves in Pulaski Co., Missouri, were kept as larvae or induced to transform in darkness or continuous fluorescent illumination. Larvae maintained in darkness for 215 and 279 days had smaller eyes, smaller rod inner and outer segments, and fewer metaphase figures in the germinative zone of the neural retina than comparable larvae maintained in light (258 lux). Except for visual cell size, differences were small and for each characteristic exceptions were observed. One larva kept in light showed early retinal degeneration comparable to that in transformed adults to T. spelaeus. All larvae exhibited optomotor behavior both before and after the experiment. Among animals induced to transform by L-thyroxin and maintained in darkness 111 to 366 days, visual cell and pigment epithelium degeneration was more extensive and more frequent than in animals kept for the same length of time in light (237-298 lux). In darkness the frequency of animals with retinal degeneration increased between 111 and 366 days. In light some animals exhibited pigment epithelium reduction with normal visual cells, and others had free, pigmented cells in the subretinal space. These effects were not comparable to degeneration in darkness. Eyelids covered the eyes of only a few animals in both light and dark treatments. The extent of eyelid encroachment over the eye greater in darkness than in light. Most animals exhibited optomotor responses after experiments, but responses of animals kept in darkness were impaired in comparison to those of animals kept in light.

Animals↗

PubMed1976

Sperm associations in the male reproductive tract of Eurycea longicauda (Amphibia: Caudata).

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Animals↗