PubMed · 6800546
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M Drury, K Sabbagh. 1982-02-20. Many a slip.. https://doi.org/10.1136/bmj.284.6315.563
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Mixture toxicity studies in dual combinations for three metals, tributyltin chloride, dibutyltin dichloride, and tin chloride, and one experiment using all chemicals were performed using the bioluminescent marine bacterium Vibrio harveyi as the test organism in a direct toxicity test procedure. Combination toxicity was evaluated using an additive index equation method and two isopleth procedures, isobole plot and isobologram. Additive index values were determined at both estimated effective median concentration (EC50) and one-third EC50 values for each dual combination and all three chemicals for one-third EC50 values. Isopleths employed chemical combinations at 20% intervals of the EC50 concentrations. Additive index values for various mixtures were either additive or antagonistic (less than additive). Isobolograms for all mixtures were descriptively additive or synergistic (greater than additive). Isobole plots were also descriptively additive or synergistic, although a few measurements were statistically different for synergism. Statistical evaluation between mixtures and single values, using the z test, were in some cases different at the 5% level. Bioluminescent counts were determined to be normally distributed using a statistical test for small sample numbers at the 1% level. Evaluation for outliers, using the Dixon test, was also performed and found one mixture to have an outlier. This single outlier had no influence on the combined toxicity results. The use of low-cost and rapid bioluminescent microbial toxicity tests for mixture studies is discussed.
The field of immunosuppression has entered a new era of sophistication, enabling investigators to selectively target specific pathways within the immune system. Recent advances offer hope that rejection after transplantation may be prevented or treated more effectively than ever before. Expanded understanding of the intracellular activities produced by immunotherapy provides a crucial foundation for clinical practice in transplant medicine. More than 25 drugs are currently under investigation for treatment of rejection, with several already undergoing clinical trials. Because they have limited actions, it is unlikely that any single agent ever will be able to control all components of the immune response. Advantages of combination therapy are, therefore, well established. Paramount to the success of this approach is the ability to select drugs with complementary mechanisms of action and without excess toxicities and unfavorable interactions. Mycophenolate mofetil (CellCept), a novel immunosuppressant for treatment of acute rejection after renal transplantation, holds great promise toward producing successful outcomes.