Quinine the Quechua, who are indigenous to Peru, Bolivia and Ecuador, to halt shivering due to low temperatures. The Quechuas would mix the ground bark of cinchona trees with sweetened water to offset the bark's bitter taste, thus producing tonic water. The Jesuits were the first to bring cinchona to Europe. The Spanish were aware of the medicinal properties of cinchona bark by the 1570s or earlier: Nicolás Monardes (1571) and Juan Fragoso (1572) both described a tree that was subsequently identified as the cinchona tree and whose bark was used to produce a drink to treat diarrhea. Quinine has been
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