Cinchona in the year 1851. Mr. [Thaddäus] Haenke mentioned the existence of cinchona bark on his visit to Yuracares in 1796". (Source: Exploration of the Valley of the Amazon, by Lieut. Lardner Gibbon, USN. Vol.II, Ch.6, pp. 146-47.) The cultivation of cinchona led from the 1890s to a decline in the price of quinine but the quality and production of raw bark by the Dutch in Indonesia led them to dominate world markets. The producers of processed drugs in Europe (especially Germany) however bargained and caused fluctuations in prices which led to a Dutch-led Cinchona Agreement in 1913 that ensured a
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