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[Salicylism and glaucoma: reciprocal augmentation of the toxicity of acetazolamide and acetylsalicylic acid].

We report a case of salicylism caused by association of acetylsalicylic acid (ASA) and acetazolamide. A 50-year-old woman without chronic renal insufficiency, was admitted for confusion, cerebellar ataxia associated with hyperchloremic acidosis. She was treated with acetazolamide for simple glaucoma and since 14 days with ASA for acute pericarditis. Clinical features evoked salicylism despite low serum salicylate level: 178 mg/l. The carbonic anhydrase inhibitor explained the biochemical pattern. Acetazolamide-induced acidosis enhances the non ionized form of salicylate which crosses the biological membrane more rapidly and better than the ionized form. The tissular tropism of non ionized salicylate increases and cerebral toxicity may occur with low serum level of ASA. ASA also enhances the free form of acetazolamide.

Acetazolamide↗

The study of the bioavailability of coated acetylsalicylic acid in suppositories after rectal administration.

The rate of release of acetylsalicylic acid (ASA) coated and uncoated from suppositories in vitro, and the bioavailability of ASA in vivo were examined. The coating reduces the rate of release of activite drug from suppositories. In vivo the coating delays the obtention of the maximum concentration of salicylates in urine, but doesn't have any essential effect on cummulative amount of salicylates in urine.

Adult↗

[Endoscopic studies of gastroduodenal tolerance of 100 mg versus 500 mg acetylsalicylic acid daily: a randomized double-blind study with healthy probands].

Acetylsalicylic acid (ASS) is increasingly used in the prevention of cardiovascular diseases. In recent years lower daily ASS-doses (100-300 mg) have been given for this indication. However, only marginal knowledge is available about the upper GI-tolerability of ASS in this dosage regiment. In a randomized double-blind study we have evaluated the gastroduodenal tolerability of 100 mg ASS and 500 mg ASS daily in 20 healthy volunteers using upper GI-endoscopy. Both ASS-dosages have been taken over a period of 4 weeks. Endoscopic controls were performed at entry and repeated after 7, 14 and 28 days of treatment. 100 mg ASS daily induced during the whole period significant less gastroduodenal damages than 500 mg ASS daily (p less than 0.05). The lesion score of both groups on day 7 and day 28 were almost identical. Our data suggest that even low doses of ASS (100 mg daily) produced gastroduodenal injuries and that no adaptative phenomena did occur during the treatment period.

Adult↗

Effects of acetylsalicylic acid on reproductive organs of adolescent male rats.

The effects of acetylsalicylic acid (ASA) at a dose of 800 micrograms/day per rat for 7 days on some androgenic parameters such as organ weights, succinate dehydrogenase, acid phosphatase, fructose, cholesterol and protein of testis, epididymis, vas deferens and accesory glands in adolescent male rats were investigated. The semen characteristics and scanning electron microscopy (SEM) study on sperm morphology of cauda epididymis were also carried out. The results revealed that the treatment manifested a marked effect in altering the metabolism of testis, cauda epididymis, seminal vesicle and vas deferens. The androgen antagonistic and antianabolic effects were by and large transient and reversible by ascorbic acid administration.

Acid Phosphatase↗

Effect of acetylsalicylic acid on prostacyclin production in trophoblast.

In attempt to elucidate whether acetylsalicylic acid (ASA) has an in vivo effect on prostacyclin (PGI2)-like activity released from trophoblast we have evaluated PGI2-like activity in pregnant women scheduled for pregnancy termination after ASA ingestion. Following subjects were studied: Group I: 7 healthy pregnant women who were treated with 1.5 g ASA for two days; Group II: 18 control pregnant women who received placebo for two days. Trophoblast specimens were obtained by legal abortions; PGI2-like activity in trophoblast was measured by the method of Moncada. In normal pregnant women (8-10 weeks gestation) treated with ASA the mean PGI2-like activity of trophoblast significantly decreased compared to the controls. These data indicate that treatment with ASA of early pregnant women might have a harmful effect on trophoblast and the problem should be further explored before allowing the administration of cyclooxygenase inhibiting drugs during early pregnancy.

Adult↗

Low dose of acetylsalicylic acid prolongs refractory periods in normal cat myocardium.

The effect of acetylsalicylic acid (ASA, Aspisol) upon diastolic threshold and refractory period in normal myocardium was investigated in the experiments on cats. It has been found that ASA given in a dose of 7 mg/kg i.v. significantly prolongs refractory period up to 27.7% of initial value throughout 2 h or observation. No significant changes in diastolic threshold were detected. Since the prolongation of refractory period favours stabilisation of cardiac rhythm, this effect of ASA may contribute to antiarrhythmic action of this drug observed earlier by other authors.

Animals↗

Effects of acetylsalicylic acid on plasma lipids and on post-heparin lipase activities.

Acetylsalicylic acid (ASA) was administered orally at the dose of 3 g a day for 2 days to healthy subjects. Plasma free fatty acids, serum triglycerides and prebetalipoproteins were significantly decreased, while cholesterol, beta and alpha 1 lipoproteins did not change. The two fractions (protamine-resistant and protamine-inactivated) of plasma post-heparin lipoprotein lipase activity (PHLA) significantly fell after ASA. PHLA diminution was reproduced by direct addition of ASA or sodium salicylate or of plasma from individuals under treatment with ASA to post-heparin plasma of untreated subjects and is, therefore, explained by a direct inactivation. The inhibition of PHLA was not followed by a significant impairment of the removal of circulating triglycerides.

Adult↗

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases].

This year acetylsalicylic acid (aspirin) celebrates its 100-year anniversary. While the drug was previously used mainly as an antipyretic and a pain-killer, aspirin has, during the last 10-15 years, become one of the most important agents in the treatment of cardiovascular and cerebrovascular diseases. In addition to being one of our oldest drugs, aspirin is one of the most interesting and widely used remedies. The antithrombotic property of aspirin is mainly related to its irreversible inhibition of the production of platelet-derived thromboxane A2, which possesses aggregatory and vasoconstrictive properties. Aspirin reduces the risk in patients with overt cardiovascular and cerebrovascular diseases, i.e. chronic stable and unstable angina pectoris. It also reduces the risk in the acute phase of and following a myocardial infarction and after a transient ischemic attack or stroke. The use of the drug is controversial in primary cardiovascular prevention. Overall mortality is not reduced, and side-effects, such as increased bleeding tendency, may be serious. This side-effect is dose-dependent, and smaller doses (75-160 mg) which have the same effect as higher doses should be preferred.

Aspirin↗

Effective of acetylsalicylic acid, indomethacin, phenylbutazone, paracetamol, ibuprofen and naproxen on canine gastric mucosa: a histological and ultrastructural study.

The effect of various non-steroidal analgesic drugs on gastric mucosal cells was studied in 48 dogs with 2 other dogs as control. Each drug was instilled into the stomach of 8 anaesthetised dogs through a gastrostomy. Gastric biopsies, obtained at 0, 1, 2 and 3 hours after administration of the drug, were subjected to histological and electron microscopical examination. Histological analysis did not show any significant changes in gastric mucosal cells in any of the drug-related groups as compared to controls. Electron microscopy, however, showed significant changes in the gastric mucous cells and parietal cells of all test groups, as compared to controls. Ultrastructural abnormalities in mucous cells included dilation of cisternae of endoplasmic reticulum, loss of granules and microvilli, and thickening of the mucous layer and were most pronounced with acetylsalicylic acid, moderate with phenylbutazone, indomethacin and naproxen, but mild with paracetamol and ibuprofen. Parietal cell changes consisting of reduction in the concentration of tubulovesicles, which canaliculi, were found to be severe with indomethacin and phenylbutazone, moderate with paracetamol and naproxen, but only minimal with acetylsalicylic acid and ibuprofen.

Acetaminophen↗

Prevalence and mechanism of streptokinase-induced platelet stimulation. Effect of acetylsalicylic acid.

It was recently shown that streptokinase may induce clot formation in vivo by immunoglobulin G mediated platelet stimulation. We evaluated the in vitro effect of streptokinase on platelet function in 103 subjects, of whom 52 were < or = 30 years and 51 were > or = 50 years old. Although streptokinase inhibited platelet aggregation in the majority of cases, in nine the threshold concentration of ADP required to induce irreversible aggregation decreased with streptokinase (1 million Units. l-1) by 30% or more. This observation was confirmed in five of the nine by repeated measurements indicating reproducible streptokinase-induced platelet stimulation. Among the five, two were < or = 30, and three were > or = 50 years old. In none of the five subjects did the radio allergo sorbent test detect type E immunoglobulins directed against streptokinase in the serum. In contrast, in four of the five subjects, streptokinase-induced platelet hyperaggregability was suppressed by addition of goat antibodies against human immunoglobulin G, or F(ab')2-fragments of such antibodies. Acetylsalicylic acid did not prevent streptokinase-induced platelet stimulation, but in three of five cases, led to an increase in the control threshold concentration for ADP, so that after the decrease induced by streptokinase the threshold concentration for ADP was in the same range as before acetylsalicylic acid and streptokinase administration. Thus, streptokinase led to an inhibition of platelet aggregation in the majority of subjects evaluated. In a minority of five out of 103, however, streptokinase reproducibly caused platelet stimulation, presumably mediated by immunoglobulin G.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.

A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.

Acute Disease↗

Effects of acetylsalicylic acid on heterotopic bone resorption and formation in rats.

The effects of acetylsalicylic acid (ASA) on bone metabolism have been studied in a bone transplantation model using radioisotopic and biochemical parameters. Isografts (femora) from infant inbred rats, extensively prelabeled with collagen and mineral-tracing radioisotopes, were transplanted to muscle pouches in young male rats. Bones from the opposite side of the donor rats served as nonimplanted reference bones. The recipients were given 150 mg/kg/12 h of ASA by gavage for 18 days. The serum concentrations obtained were comparable with the recommended anti-inflammatory levels in humans. Twenty-four hours before being killed the animals were labeled again with other collagen and mineral radioisotopes. After 18 days of medication the resorption of the transplanted bone was inhibited by about 15% in the ASA treated rats compared with controls, as measured by the losses of collagen (14C-hydroxyproline) and mineral (strontium-85). Also, the net gains of mineral and collagen in the ASA-treated transplants were reduced by about 15% and 11% respectively compared with controls during the medication period. During the last 24 h of the study the rates of mineral incorporation (calcium-47 uptake) and collagen synthesis (3H-hydroxyproline) were reduced to an even greater degree in the ASA-treated transplants. These results indicate an inhibitory effect of ASA on bone metabolism.

Animals↗

Role of the double-contrast barium enema in rectal stenosis due to suppositories containing paracetamol and acetylsalicylic acid.

Self-treatment of chronic headache with suppositories containing paracetamol and acetylsalicylic acid may lead to serious complications. We report the radiological features of five cases of rectal stenosis following the use of such suppositories. The role of the double-contrast barium enema in suggesting the diagnosis of this complication of a chronic and often unrecognized self-treatment is emphasized.

Adult↗

Acetylsalicylic acid as antifungal in Eremothecium and other yeasts.

Interesting distribution patterns of acetylsalicylic acid (ASA, aspirin) sensitive 3-hydroxy (OH) oxylipins were previously reported in some representatives of the yeast genus Eremothecium--an important group of plant pathogens. Using immunofluorescence microscopy and 3-OH oxylipin specific antibodies in this study, we were able to map the presence of these compounds also in other Eremothecium species. In Eremothecium cymbalariae, these oxylipins were found to cover mostly the spiky tips of narrowly triangular ascospores while in Eremothecium gossypii, oxylipins covered the whole spindle-shaped ascospore with terminal appendages. The presence of these oxylipins was confirmed by chemical analysis. When ASA, a 3-OH oxylipin inhibitor, was added to these yeasts in increasing concentrations, the sexual stage was found to be the most sensitive. Our results suggest that 3-OH oxylipins, produced by mitochondria through incomplete beta-oxidation, are associated with the development of the sexual stages in both yeasts. Strikingly, preliminary studies on yeast growth suggest that yeasts, characterized by mainly an aerobic respiration rather than a fermentative pathway, are more sensitive to ASA than yeasts characterized by both pathways. These data further support the role of mitochondria in sexual as well as asexual reproduction of yeasts and its role to serve as a target for ASA antifungal action.

Aspirin↗

Differential effects of oral administrations to human volunteers of acetylsalicylic acid, sodium salicylate and indomethacin on 12-hydroxyeicosatetraenoic acid formation by stimulated platelets.

The effects of single oral administrations of acetylsalicylic acid (ASA, 500 mg), indomethacin (Indo, 50 mg) and sodium salicylate (NaSal, 400 mg) on platelet aggregation and on the thromboxane B2 (TXB2) and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis by platelet rich plasma (PRP) stimulated with collagen were evaluated. While both ASA and Indo significantly inhibited TXB2 synthesis and platelet aggregation, significant reduction of 12-HETE formation at 2 and 6 h after the administration of the drug, was detected only in subjects who ingested ASA. NaSal did not affect any of the tested parameters. The comparison of the effect of ASA (200 mg) on 12-HETE synthesis in washed platelets and PRP shows that the drug is able to affect this parameter only in PRP. To obtain a constant inhibition of 12-HETE synthesis in PRP over a 24 h period, a repeated ASA treatment schedule was assessed (ASA 200 mg every 6 h for 5 times). TXB2 synthesis in PRP was almost completely suppressed at 2 h after the first ASA administration and inhibition remained constant up to 48 h after the last ASA intake. As far as 12-HETE synthesis by stimulated PRP is concerned, a significant reduction of this parameter was detected at 4 h after the first drug administration and the levels remained almost constant following the repeated administrations during a 24 h period. These data indicate that ASA, but not Indo and NaSal, significantly affect not only TXB2 synthesis but also 12-HETE formation in PRP. The lack of the effect of ASA administration on 12-HETE, found when studies were carried out in washed platelets, indicates that the drug requires the presence of plasma factors for its activity on the formation of 12-lipoxygenase products by platelets.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Glucose-6-phosphate dehydrogenase from Saccharomyces cerevisiae: characterization of a reactive lysine residue labeled with acetylsalicylic acid.

Glucose-6-phosphate dehydrogenase from Saccharomyces cerevisiae (bakers' yeast) reacts with acetylsalicylic acid, and this is accompanied by inactivation and modification of essentially one lysine residue per subunit. The amino acid sequence of an 11-residue tryptic peptide containing the reactive lysine residue of the yeast enzyme is given and establishes the existence of different subgroups of glucose-6-phosphate dehydrogenases. Thus, the labeled yeast structure has few similarities to the known structure around the reactive lysine residue of the enzyme from Leuconostoc mesenteroides, although it has extensive similarities with a structure in the human enzyme. It is further shown that amino acid sequences around reactive lysine residues of dehydrogenases in general vary, even though similarities occur around reactive lysine residues in 6-phosphogluconate, glutamate, and glyceraldehyde-3-phosphate dehydrogenases.

Amino Acid Sequence↗