Dementia
Although cohort and longitudinal studies have shown low-dose aspirin has a greater likelihood of reducing the incidence of dementia, numerous randomised controlled trials have not validated this. Other uses
Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease. Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children in spite of a lack of high quality evidence for its effectiveness.Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia. This benefit is greater when started in early pregnancy. Resistance
For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin-resistance or insensitivity. One study has suggested women are more likely to be resistant than men, and a different, aggregate study of 2,930 people found 28% were resistant. A study in 100 Italian people found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant. Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".
That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005, and fine structural details were given by Bond et al. A new crystal type was found during experiments after co-crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups, both polymorphs form identical dimer structures. Mechanism of action
Discovery of the mechanism
In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes. For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune Bergström and Bengt Ingemar Samuelsson. Prostaglandins and thromboxanes
Aspirins ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-endoperoxide synthase, PTGS) enzyme required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the PTGS enzyme (Suicide inhibition).