Epidemiological studies found that Dow had been adding cobalt sulfate to the beer for foam stability since July 1965 and that the concentration added in the Quebec city brewery was ten times that of the same beer brewed in Montreal where there were no reported cases. A 1972 paper noted that several dozen cases were also identified over a similar time period in Omaha, Nebraska; Minneapolis, Minnesota; and Belgium. Cobalt in the environment
Plants, animals, and humans can all be affected by high cobalt concentrations in the environment. For plants, the uptake and distribution of cobalt is entirely species-specific. In some species of plants, the overaccumulation of cobalt can lead to an iron deficiency. This in turn leads to poor growth of the plant as well as leaf loss which overall decreases the amount of oxygen produced by plants during photosynthesis. Eventually the deficiency would lead to plant death. One such example was seen in an experiment involving the effects of increased cobalt concentration on tomato plants. As the dosage of cobalt in the soil surrounding the plants increased, so too did the rate of necrosis of the leaves of the tomato plant. Over time this led to an inability of the plant to produce fruit and eventually the plant died. References


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Tivozanib, sold under the brand name Fotivda, is a medication used for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). It is an oral VEGF receptor tyrosine kinase inhibitor.The most common side effects include fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis.Tivozanib was approved for medical use in the European Union in August 2017, and in the United States in March 2021. Medical uses
Tivozanib is used for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Contraindications
Tivozanib must not be combined with St. Johns Wort, an inducer of the liver enzyme CYP3A4 (see interactions below). It should not be taken during pregnancy as it is teratogenic, embryotoxic and fetotoxic in rats. Adverse effects
The most common side effects in studies were hypertension (high blood pressure, in 48% of patients), dysphonia (hoarse voice, 27%), fatigue and diarrhoea (both 26%). A hypertensive crisis occurred in 1% of patients. Interactions
Administration of a single dose of tivozanib with rifampicin, a strong inducer of the enzyme CYP3A4, cuts the biological half-life and total exposure (AUC) of tivozanib in half, but has no relevant influence on highest concentrations in the blood. Combination with ketoconazole, a strong CYP3A4 inhibitor, has no relevant effects. The clinical significance of these findings is not known. Pharmacology
Mechanism of action
A quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor (VEGF). It is designed to inhibit all three VEGF receptors.