Aspirin studies

G. Ahbrandi, N. Micab, S. Trusso, A. Villari, Hydrolysis of Aspirin Studied by Spec-trophotometric and Fluorometric Variable-Temperature Kinetics , J. Pharm. Sci. 1996, 85, 1105-1108. 

This ruggedness test provided a greater challenge to the method than did the test conditions of the aspirin studies, most factors being tested to larger extreme values. 

The experimental order of this study was also changed from the ideal randomised and blocked design. This was justified for reasons of automation where column changes needed to be minimised. As for the aspirin study the validity of this compromise depends on the fact that the repeatability of the method, over a time span such as that required for the ruggedness test, had previously been established. 

Alibrandi, G., Micali, M., Trusso, S., and Villari, A. (1996), Hydrolysis of aspirin studied by spectrophotometric and fluorometric variable-temperature kinetics, I. Pharm. Sci., 85, 1105-1108. 

However, that aspirin study showed me that we have not learned from the past. I know that we are anxious on many fronts to try to make sure that there is a diverse population and that there are such studies, but I think we still have a long way to go. 

Alemany M, Hernandez MR, Bozzo J, Bono A, Escolar G, Ordinas A, Bastida E A ddderious effect of aspirin on the antithrombotic properties of endothelial cdls is not observed with platdets previously exposed to aspirin Studies in a flow system. Platelets 7 29-34,1996. 

Hass WK, Easton JD, Adams HP, et al, for the Ticlopidine Aspirin Study Group. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med 1989 321 501-507. 

In Section 4D.2 we introduced two probability distributions commonly encountered when studying populations. The construction of confidence intervals for a normally distributed population was the subject of Section 4D.3. We have yet to address, however, how we can identify the probability distribution for a given population. In Examples 4.11-4.14 we assumed that the amount of aspirin in analgesic tablets is normally distributed. We are justified in asking how this can be determined without analyzing every member of the population. When we cannot study the whole population, or when we cannot predict the mathematical form of a population s probability distribution, we must deduce the distribution from a limited sampling of its members. 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

The case of intramolecular participation in ester hydrolysis has been extensively studied using acetylsalicylic acid (aspirin) and its derivatives. The kinetic data show that the anion is hydrolyzed more rapidly than the neutral species, indicating that the carboxylate group becomes involved in the reaction in some way. Three mechanisms can be considered ... 

Arcus and co-workers94 studied alkaline hydrolyses of neutral and anionic aliphatic esters in the presence of poly (vinylbenzyltriethylammonium hydroxide), 42 (PVBzTEA), as a catalyst. Baumgartner and associate95 also found enhanced alkaline hydrolyses of 43 (aspirin, anionic substrate), in the presence of 42 (PVBzTEA), in alkaline pH regions. 

Dipyridamole is a PDE5/PDE6 selective inhibitor that is used widely in conjunction with aspirin to reduce clotting and prevent stroke. More recent studies with a fixed combination of these two drugs (Aggrenox) has been shown in the recent European Stroke Prevention Study 2 to be of greatly added benefit over aspirin alone for prevention of recurrent stroke. 

Studies suggest that the use of salicylates (especially aspirin) maybe involved in the development of Reye s syndrome in children with chickenpox or influenza. This rare but life-threatening disorder is characterized by vomiting and lethargy, progressing to coma. Therefore, use of salicylates in children with chickenpox, fever, or flulikesymptomsisnot recommended. Acetaminophen is recommended for the management of symptoms associated with these disorders... 

A non-allergic mechanism imderlying precipitation of asthmatic attacks by aspirin in hypersensitive patients was proposed over 30 years ago [4]. It was founded on pharmacological inhibition of COX of arachidonic acid and explained a cross-reactivity between different NSAIDs varying in chemical structure. This COX theory was confirmed by several studies [11] and was further refined following discovery of the second COX isoenzyme - COX-2. At least two COX isoenzymes, COX-1 and COX-2, are coded by separate genes. Their role in inflammation, asthma and anaphylaxis has been reviewed previously [12]. 

Samter M, Beers RF Jr Intolerance to aspirin. Chn-ical studies and consideration of its pathogenesis. 

Neural networks have also been used in Slovenia, to model the release characteristics of diclofenac [52] in China, to study release of nifedipine and nomodipine [53] and in Yugoslavia to model the release of aspirin [54], More recently, work in this area has been extended to model osmotic pumps in China [55] and enteric coated tablets in Ireland [56],... 

A recent study compared 144 patients treated within 6 hours of symptom onset with I AT using urokinase versus 147 patients treated with aspirin who were matched for age and stroke severity according to National Institutes of Health Stroke Scale (NIHSS) (median 14). The study demonstrated superiority of LAT to aspirin in patients achieving an mRS score of 0-2 (56% vs. 42%, p = 0.037) and in patients achieving an mRS score of 0-1 at 2 years (40% vs. 24%, p = 0.008) with no difference in mortality (23% vs. 24%). °... 

The GP Ilb-IIIa complex inhibitor Tirofiban has been used as an adjunct to thrombolysis in a number of small case series reports." A small transcranial Doppler (TCD) study suggests that it reduces microembolization from unstable carotid plaque." In an open pilot smdy, Tirohban administered within 9 hours after stroke onset blocked the conversion of ischemic penumbra to mature infarction." A phase III study (SETIS) has started recruiting patients to investigate its efficacy versus aspirin within the 6-hour window. 

In the Multicenter Acute Stroke Trial Italy (MAST-I) study, 622 patients were randomized in a 2 X 2 factorial design to receive either a 1-hour infusion of 1.5 lU streptokinase or 300 mg aspirin or both, or neither. Streptokinase (alone or with aspirin) was associated with a greater number of fatahties at 10 days (OR 2.7,95% Cl 1.7. 3). In MAST-I, neither aspirin monotherapy nor combination therapy reduced the primary outcome of combined 6-month fatahty and severe disability. 

The European Stroke Prevention Study 2 (ESPS-2) trial examined four treatment arms—extended-release dipyridamole (ER-DP) 200 mg twice daily alone, aspirin 25 mg twice daily alone, ER-DP 200 mg twice daily + aspirin 25 mg twice daily, or placebo. In comparison with placebo the overall reduction in stroke risk was 16% with ER-DP alone and 18% with aspirin alone. The combination of ER-DP and aspirin led to a 37% reduction in stroke risk compared to placebo. Compared with aspirin alone, the combination of ER-DP with aspirin reduced the risk of stroke by 23%. 

Berge E, Abdelnoor M, Nakstad PH, Sandset PM, on behalf of the Haest Study Group. Low molecular-weight heparin versus aspirin in patients with acute ischemic stroke and atrial fibrillation a double blind randomised study. Lancet 2000 335 1205-1210. 

Cote R, Battista RN, Ahrahamowicz M, Langlois Y, Bourque F, Mackey A. Lack of effect of aspirin in as3miptomatic patients with carotid hmits and substantial carotid narrowing. The Asymptomatic Cervial Bruit Study Group. Ann Intern Med 1995 123 649-655. 

ESPRIT Study Group, Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT) randomised controlled trial. Lancet 2006 367(9523) 1665-1673. 

The third study was the Physicians Health Study, in which 22,071 US male physicians were randomised to get either 50 mg P-carotene or 325 mg aspirin, or both, or neither, every other day for 12 years. There was no evidence of a significant beneficial or harmful effect on cancer or cardiovascular... 

Gastric mucosal injury induced by non-steroidal antiinflammatory drugs such as aspirin and indomethacin has also been extensively studied, again with somewhat conflicting results. Several studies have shown a protective effect of SOD, catalase, hydroxyurea and desferrioxamine (Takeuchi et al., 1991a Vaananen et al., 1991 Naito et al., 1992). Del Soldato etal. (1985) also found aminopy-rine, thiourea and its derivative, MK 447, and SAZ to be protective. Allopurinol has been shown to be both protective (Takeuchi etal., 1991a) and ineffective (Vaananen etal., 1991). 

Recent studies have suggested that combination antiplatelet therapy may be synergistic in reducing the risk of IHD-related events. In patients with ACS, the combination of aspirin and clopidogrel 75 mg daily for up to 9 months was more effective than aspirin alone in decreasing the risk of... 

Aspirin in acute ischemic stroke has been studied in two large, randomized trials, the International Stroke Trial and the Chinese Acute Stroke Trial.20,21 Patients who received aspirin within 24 to... 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

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