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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an in vitro system designed to measure arterial constriction, we have demonstrated the importance of platelet function in maintaining cerebral smooth muscle contraction after whole blood injection. We tested two agents, acetyl salicylic acid (ASA) and phthalazinol, both known to interfere with platelet function. In control tests normal rabbit and monkey blood produced a reliable and persistent arterial constriction. In experimental tests blood drawn from animals premedicated with ASA and phthalazinol failed to produce a persistent contraction. These results support the hypothesis that chemicals released during platelet aggregation may be important in persistent vasospasm.
Stroke
PMID:Prevention of persistent cerebral smooth muscle contraction in response to whole blood. 10 Sep 6

Aspirin (acetylsalicylic acid) and its salicylate derivatives are effective antipyretic, analgesic, and anti-inflammatory agents that are still very widely used by the elderly despite the advent of newer, potentially safer nonsteroidal anti-inflammatory drugs (NSAIDs). However, none of the new NSAIDs have been proven to be more effective than aspirin or salicylic acid. Chronic salicylate intoxication which is most common in the elderly, may occur with therapeutic doses. Increased toxicity in older patients often appears due to inadvertent overdosage. Dual prescribing or additional use of nonprescription salicylates are some causes of unwitting long term toxicity. According to some studies, systemic clearance of salicylate (mainly by hepatic metabolism) is reduced with age, as is renal elimination. These changes are of increased importance in the elderly using high therapeutic doses of salicylates when metabolism is saturated and more unchanged drug is available for renal excretion. In the face of renal impairment, the risk of toxicity is increased. The diagnosis of acute salicylate intoxication generally does not pose diagnostic problems. Patients often present with a history of intentional overdose, with hyperventilation, fever, and nausea. The diagnosis can be confirmed by measuring serum salicylate concentrations. Chronic intoxication often poses a diagnostic dilemma with atypical presentations mimicking other disease states such as diabetic ketoacidosis, delirium, cerebrovascular accident, myocardial infarction or cardiac failure. The diagnosis of salicylate intoxication should be borne in mind when an older patient presents with recent deterioration in activities of daily living with no known cause. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there is no documented history of salicylate ingestion. The risk of salicylate nephrotoxicity is also increased with age, and upper gastrointestinal haemorrhage is associated with increased mortality in older age groups. Treatment of acute toxicity consists of prompt recognition of salicylate intoxication, use of activated charcoal, correction of acid-base abnormalities, general supportive measures, and if concentrations are extremely high, dialysis can be effectively used. Chronic toxicity, which can occur even with marginally high salicylate concentrations, is treated with drug withdrawal and supportive therapy. Chronic salicylate toxicity can be averted by prescription of conservative doses of drug, avoidance of concomitant use of different salicylate preparations, and therapeutic monitoring to guide dosage. Renal function should be monitored to detect nephrotoxicity from chronic salicylate therapy. Patients should be regularly screened for evidence of gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. 155 71

The relationship of the transports between acidic drugs and monocarboxylic acids through the blood-brain barrier (BBB) was examined using the carotid artery injection technique in rats. The BBB uptakes of [3H]acetic acid and [14C]salicylic acid were significantly reduced by the presence of the respective unlabeled compounds, valproic acid, lactic acid, benzoic acid, nicotinic acid or beta-lactam antibiotics (benzylpenicillin, propicillin and cefazolin), but was not reduced by choline, phenylalanine and a basic drug, eperisone. A remarkable pH dependency was observed for the BBB uptake of [14C]salicylic acid at the pH region of 4.0 to 7.4. Interestingly, 10 mM of salicylic acid diminished significantly the pH dependent BBB uptake of [14C]salicylic acid. Similar results were obtained in the BBB uptake of [14C]nicotinic acid. No significant difference was observed in the transport of monocarboxylic acids through the BBB between normotensive Wistar KY rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). From these observations, acidic drugs could be transported by a carrier-mediated system for monocarboxylic acids at the BBB and the transport system was not changed by the disease state.
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PMID:Acidic drug transport in vivo through the blood-brain barrier. A role of the transport carrier for monocarboxylic acids. 211 62

This investigation includes 17,187 patients in 417 hospitals in 16 countries admitted within 24 hours of the commencement of symptoms of acute myocardial infarction (AMI). The patients were allotted at random to the following treatments 1) intravenous infusion of 1.5 million International Units streptokinase (SK) during one hour, 2) 160 mg acetyl salicylic acid (ASA) daily for 30 days, 3) both SK and ASA and 4) placebo treatment only. The five-week cardiovascular mortality was reduced by 25% following infusion of streptokinase from 12.0% to 9.2% and by 23% during ASA treatment from 11.8% to 9.4%. The combination of SK and ASA resulted in 42% reduction in the cardiovascular mortality after five weeks compared with the placebo. The effect of SK was greatest if treatment was instituted within six hours but effects were obtained after all of the first 24 hours. The preliminary results show that the reduction in mortality obtained by both SK and ASA appears to continue during the subsequent one to two years. SK treatment resulted in haemorrhage requiring treatment in 0.5% as compared with 0.2% in the placebo group, more cases of proved cerebral haemorrhage, 0.1% as compared with 0.0%, but fewer cases of cerebral apoplexy, 0.7% as compared with 0.8%. It is concluded that thrombolysis with SK combined with prophylaxis of repeated thrombosis with ASA is the indicated treatment in cases of AMI and less than 6-24 hours duration.
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PMID:[Reduction of mortality in acute myocardial infarction with streptokinase and aspirin therapy. Results of ISIS-2]. 268 81

Enteric-coated formulations of acetylsalicylic acid (ASA) should be advantageous in prophylaxis after stroke because they cause fewer gastrointestinal side effects. However, the absorption of unchanged ASA and the effectiveness of these formulations have been questioned, which prompted the present investigation. Fourteen elderly stroke patients on long-term medication with enteric-coated ASA 1.5 g daily and four patients on placebo were studied. When tested with arachidonic acid platelet aggregation was completely inhibited in all ASA subjects whereas it was normal in the controls. Plasma samples, drawn every 1/2 h for 6 h after tablet intake, were analyzed by HPLC. The presence of ASA was short lasting with a mean peak concentration of 55 mumol/l reached after 2-3.5 h. Salicylic acid (SA) appeared later, having a mean peak value of 591 mumol/l after 2.5-6 h. Thus, absorption of ASA as well as inhibition of platelet aggregation were confirmed during long-term medication with enteric-coated ASA.
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PMID:Platelet aggregation and plasma levels of acetylsalicylic acid in stroke patients on long-term treatment with an enteric-coated aspirin formulation. 651 Apr 66

Aspirin is used for the prophylaxis of infarction. A low dose of aspirin is effective for the prophylaxis of myocardial infarction, whereas a higher dose is necessary for that of stroke. Salicylic acid, the in vivo metabolite of aspirin, inhibits the beta-oxidation of short-chain fatty acids. Accordingly, drinking water containing 400, 800, or 1200 mg/l aspirin was given to each of eight rats for 30 days to determine the serum short-chain fatty acid levels. Analysis of variance and a post-hoc Fisher's protected least significant differences test revealed significantly increased levels (P < 0.05) of monocarboxylic acids, n-hexanoate, n-octanoate, n-decanoate, n-dodecanoate, and dicarboxylic acids, adipate (C6,) and suberate (C8): 78.7 +/- 36.2, 61.1 +/- 30.6, 215 +/- 151, 47.5 +/- 24.0, 3.64 +/- 2.09 and 1.71 +/- 1.45 micromol/l in the 800 mg/l aspirin group compared to 23.8 +/- 12.3, 20.1 +/- 9.0, 24.3 +/- 12.1, 6.3 +/- 5.6, 0.56 +/- 0.50 and 0.44 +/- 0.25 micromol/l in the control group, respectively. These levels were also increased in the 400 or 1200 mg/l aspirin groups but less so. These findings may help us to understand the aspirin toxicity in Reye's syndrome.
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PMID:Aspirin induces short-chain free fatty acid accumulation in rats. 966 95

The aim of the HOT Study (Hypertension Optimal Treatment) was to determine the optimal diastolic blood pressure decrease and to assess the effect of the acetyl salicylic acid as a primary prevention on the cardiovascular morbidity and mortality in hypertensive patients. The HOT Study is an open, prospective, randomised, international trial with blinded end points. This study included 18,790 patients, 50 to 80 years old (mean 61.5 years) in 26 countries (1,574 patients in France) with a primary hypertension (100 < or = PAD < or = 115 mmHg). The patients were randomised in 3 target diastolic blood pressure: < or = 80 mmHg (n = 6,262), < or = 85 mmHg (n = 6,264), < or = 90 mmHg (n = 6,264). The felodipine LP, a long acting dihydropyridine, was selected as a first line therapy, other hypertension drugs combined if necessary. The lowest incidence of cardiovascular events was observed at a diastolic blood pressure level of 82.6 mmHg. There was no increased risk below this level even in the hypertensive patients with medical history of coronary heart disease or stroke. In the diabetic population, the diastolic blood pressure decrease from 90 to 80 reduced the incidence of the major cardiovascular events by 51%. The acetyl salicylic acid reduced the myocardial infarction risk in the blood pressure well-controlled population.
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PMID:[Effect of intensive antihypertensive treatment and of aspirin in a low dose in the hypertensive. The HOT (Hypertension Optimal Treatment) study]. 1048 68

Atrial fibrillation is a common arrhythmic disorder which is becoming increasingly prevalent among the elderly. Atrial fibrillation is an independent risk factor for ischaemic stroke. Patients with hypertension, heart failure, diabetes, age older than 65 years, previous thromboembolisms, left atrial enlargement and left ventricular dysfunction have an increased risk. Coumarins (with a target international normalised ratio (INR) of 2.0 to 3.0) are the treatment of first choice in patients with atrial fibrillation. In young patients without additional risk factors, acetyl salicylic acid provides sufficient protection. The management of anticoagulant therapy during electric cardioversion in the acute phase of an ischaemic stroke and during elective surgical interventions, is still a subject of clinical research.
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PMID:[Anticoagulant treatment of patients with atrial fibrillations: dependent on age and other risk factors for thromboembolism]. 1262 83

This article describes the historic roots of acetylsalicylic acid (ASA) from the first experiments at 1800 until the introduction into the pharmaceutical market in 1899. In 1869, Hermann Kolbe enlightened the chemical structure of salicylic acid, which was used at that time as an analgetic and antipyretic drug. Because of the side effects, for example the irritation of the stomach, analytical chemists and pharmacologists searched for chemical modifications. In August 1897 Felix Hoffmann (1868-1946) was successful in acetylizing the salicylic acid to acetylsalicylic acid (ASA). Between 1897 and 1899 Kurt Witthauer (1865-1911) collected clinical data and experiences on the efficiency of ASA as an analgetic and antipyretic drug. In 1899 ASA was introduced into the pharmaceutical market as Aspirin and became soon one of the most successful drugs of its time. The indication exceeds analgesia in the mean time and to prophylaxis of myocardial ischaemia or cerebral stroke, among others.
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PMID:[A pharmaceutical of the century will be 100. A historical vignette on the introduction of acetylsalicylic acid to the market in 1899]. 1279 22

Acetylsalicylic acid (ASA) reduces the incidence of ischemic stroke mainly through its antithrombotic action; however, it also has a direct neuroprotective effect. The present study was designed to evaluate the effect of ASA on oxidative stress and the activity of nitric oxide synthase (NOS) in an in vitro model of hypoxia in rat brain slices. Rat brain slices were perfused with nitrogen (hypoxia) for a maximum of 120 min, after which we measured lipid peroxidation, glutathione levels, glutathione-related enzyme activities, and constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) activities. In brain tissue subjected to hypoxia, ASA reduced oxidative stress and iNOS activity (all increased by hypoxia), but only when used at higher concentrations. The effects of salicylic acid (SA) were similar but more intense than were those of ASA. After oral administration, the effect of SA was much greater than that of ASA, and the decrease in cell death with SA was seen much more clearly. In view of the greater effect of SA compared to ASA on changes in oxidative stress parameters in a model of hypoxia, and higher brain concentrations of SA when it is administered alone than when ASA is given (undetectable levels), we conclude that SA plays an important role in the cytoprotective effect in brain tissue after ASA administration.
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PMID:Antioxidant effect of acetylsalicylic and salicylic acid in rat brain slices subjected to hypoxia. 1470 49


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