Originally, nitisinone was developed as a weed-killer by Zeneca Agrochemicals. It was epidemiologically observed that the growth of plants and weeds was inhibited under the bottlebrush plant (Callistemon citrinus). It became clear that neither the shade nor the litterfall of these plants was responsible for the suppression of plant and weed growth. Rather, a substance – which was identified as leptospermone – in the soil under the bottlebrush plant was shown to have bleaching activity on the emerging plants. The allelochemical leptospermone was extracted from the bottlebrush plant and chemically characterized. Leptospermone belongs to the triketone family and inhibits chloroplast development due to a lack of plastoquinone secondary to hepatic 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition; thus, it served as a blueprint for the synthesis of nitisinone.In 1932, Grace Medes first described "a new disorder of tyrosine metabolism," She coined the condition "tyrosinosis" after observing 4-hydroxyphenylpyruvate in the urine of a 49-year-old man with myasthenia gravis. She proposed that the metabolic defect in this patient was a deficiency of 4-hydroxyphenylpyruvate dioxygenase, but her case remains puzzling and has since been assigned a separate OMIM number. The first typical patient with hepatorenal tyrosinemia was described in 1956 by Margaret D Baber at Edgware General Hospital in Middlesex, England. Starting the following year, Kiyoshi Sakai and colleagues, at the Jikei University School of Medicine in Tokyo, published 3 reports describing the clinical, biochemical, and pathological findings of a 2-year-old boy with hepatorenal tyrosinemia who was then thought to have an "atypical" case of tyrosinosis.
Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from a laceration in the mucosa at the junction of the stomach and esophagus. This is usually caused by severe vomiting because of alcoholism or bulimia, but can be caused by any condition which causes violent vomiting and retching such as food poisoning. The syndrome presents with hematemesis. The laceration is sometimes referred to as a Mallory–Weiss tear. Signs and symptoms
Mallory–Weiss Syndrome often presents as an episode of vomiting up blood (hematemesis) after violent retching or vomiting, but may also be noticed as old blood in the stool (melena), and a history of retching may be absent. In most cases, the bleeding stops spontaneously after 24–48 hours, but endoscopic or surgical treatment is sometimes required. The condition is rarely fatal. Causes
It is often associated with alcoholism and eating disorders and there is some evidence that presence of a hiatal hernia is a predisposing condition. Forceful vomiting causes tearing of the mucosa at the junction. NSAID abuse is also a rare association. In rare instances some chronic disorders like Ménières disease that cause long term nausea and vomiting could be a factor. The tear involves the mucosa and submucosa but not the muscular layer (contrast to Boerhaave syndrome which involves all the layers).