Edward Stone (natural philosopher) piece of bark from a willow tree and was struck by its extremely bitter taste. Knowing that the bark of the Peruvian cinchona tree − from which quinine (used in the treatment of malarial fevers) is derived − has a similarly bitter taste, he surmised that the willow might also have therapeutic properties. Stone's interest in willows was due to the ancient "doctrine of signatures" – whereby the cause of a disease offers a clue to its treatment. According to Stone: "As this tree delights in a moist or wet soil, where agues chiefly abound, the general maxim that many
Analgesic nephropathy of paracetamol into "N"-acetyl-"p"-benzoquinoneimine (NAPQI). NAPQI depletes glutathione via non-enzymatic conjugation with glutathione, a naturally occurring antioxidant. With depletion of glutathione, cells of the kidney become particularly sensitive to oxidative damage. Diagnosis is traditionally based on the clinical findings above in combination with excessive analgesic use. It is estimated that between 2 and 3 kg each of phenacetin or aspirin must be consumed before evidence of analgesic nephropathy becomes clinically apparent. Once suspected, analgesic nephropathy can be confirmed with relative accuracy using computed tomography (CT) imaging without contrast. One trial demonstrated that the appearance of papillary calcifications on CT imaging