The effect of acetylsalicylic acid on the metabolism and transformability of human lymphocytes in vitro.
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The effect of antiaggregating agents - acetylsalicyclic acid (ASA) and dipyridamol - on the rejection of allotransplanted canine kidneys in presensitized animals were studied. Blood flow dropped more markedly in the control group than in the group treated with ASA and dipyridamol. 24 hours after transplantation the blood flow in this group was significantly higher than in the control group (p 2,5 %) and in the third group treated with dipyridamol alone. The cellular rejection started earlier and was more pronounced in the control group. Only in this group vascular rejection and microthrombi were demonstrated. Urine output ceased 24 to 60 hours after transplantation. The immunosuppressive, antiphlogistic and platelet antiaggregating effect of the combined ASA and dipyridamol therapy is thought to be responsible for the better results in this group. In this experimental model the combined treatment of ASA and dipyridamol results in a later onset of cellular rejection, in better blood-flow of the kidney and later onset of anuria.
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Loss of autonomic balance characterized by increased sympathetic activity and decreased vagal activity has been implicated as a major cardiovascular risk factor. Aspirin's cardioprotective abilities involve a multitude of physiologic processes. However, the effects of aspirin on cardiac autonomic activity are unknown. In a double-blind crossover study, 22 subjects randomly received either aspirin or placebo in the amounts of 325 mg with each meal (three times per day) over a 2.5-day period. The total amount of aspirin ingested was 2,275 mg, which resulted in plasma levels of 3.3 mg/dl. At the conclusion of each treatment, subjects were evaluated for autonomic physiology activity using standard autonomic tests. Power spectral analyses of the electrocardiograms were used to delineate autonomic function. A 2 x 4 repeated measures analysis of variance revealed significant and favorable changes in autonomic activity after the use of aspirin. Specifically, at rest high-frequency (HF) power was significantly higher (mean, 1,090 + 1,463.5 msec2) compared with the placebo (mean, 692 742 msec2) (p <0.05). Low-frequency (LF) power was significantly reduced (mean, 963 745 msec2) after aspirin compared with placebo (mean, 1,100 906 msec2). After the aspirin treatment, a significantly lower LF-to-HF power ratio (mean, 1.7 2 msec2) was noted at rest when compared with the placebo (mean, 2.5 2.7 msec2) (p <0.05). Similar significant trends were seen during the sustained isometric contraction after aspirin therapy for HF power (mean 210 2.15 msec2) compared with placebo (mean, 213 184 msec2) (p <0.05). Accordingly, the LF-to-HF power ratio was lower as well when compared to placebo treatment (mean, 2.3 3.5 msec2) (mean, 5.3 8.4 msec2) (p <0.05). No differences were found in breathing rates for hemodynamic variables between any of the protocols. The significant reduction of LF-to-HF ratio, a marker of sympathovagal balance, for both protocols appeared to be largely due to a withdrawal of LF modulation and concomitant but lesser increase in HF modulation. Favorable alterations in autonomic outflow through prostaglandin inhibition may be one of the mechanisms by which low therapeutic amounts of aspirin provide prophylactic cardioprotection.
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BACKGROUND: A new method of intravitreal drug delivery of acetylsalicyclic acid (AS) in silicone oil was investigated for safety and for its pharmacokinetics in the posterior pole of the eye. METHODS: The AS was mixed in silicone oil to a concentration of 1.67 mg/ml. After vitrectomy, 15 NZW rabbits received an intravitreal injection of AS/silicone oil suspension. Clinical examination, pre- and postoperative electroretinography (ERG) and histology were performed. The pharmacokinetics of the distribution of salicylic acid was determined by HPLC analysis at 6 h, 24 h and 5 days in optic nerve, retina, choroid, vitreous, and blood. RESULTS: Clinical examination and histology revealed no adverse effects or signs of toxicity. The ERGs showed no significant difference between the pre- and postoperative results. The salicylic acid concentrations demonstrated peak values in the residual vitreous (640.0 micrograms/ml), choroid (446.0 ng/mg) and retina (281.3 ng/mg) at 6 h. At 24 h, the salicylic acid concentration decreased to 20.9 micrograms/ml in the residual vitreous and to 38.5 ng/mg in the retina. At 5 days the retinal level was still 48.1 ng/mg. CONCLUSIONS: AS delivery by intravitreal administration of loaded silicone oil is a safe method and results in high concentrations of salicylic acid in the posterior segment of the eye while maintaining low blood levels.
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The effects of dipyridamole and ASA on platelet functions were studied in patients with aortic ball-valve prostheses. Before ingestion, platelet adhesiveness was markedly reduced and platelet survival time slightly, but insignificantly shortened. ASA prolonged the bleeding time, reduced collagen-induced platelet aggregation, and inhibited secondary aggregation initiated by adrenalin. Similar effects were obtained with 2 Gm. of ASA alone as with 1 Gm. daily in combination with 225 mg. of dipyridamole. Platelet adhesiveness remained low. Depyridamole alone, 375 mg. daily, did not influence any of these parameters. The mean platelet half-life was prolonged from 3.52 to 3.72 days by each drug and to 4 days by the combined treatment. None of the differences was, however, statistically significant. A clinical study with ASA has been started in a larger series of patients to evaluate the effect on arterial thromboembolism.