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Mitochondrial dysfunction is increasingly associated with disease states. These organelles, responsible for adenosine triphosphate production, have been targeted for improved function in such diseases as Parkinson's, Alzheimer's, type 2 diabetes, and sarcopenia. In addition, the importance of determining if a clinical drug candidate adversely effects mitochondria function, which could lead to overt toxicity, has been recognized. Hence, assays that measure mitochondria activity have become essential in early stage drug development. Limitations of current assays that measure mitochondria membrane potential have prohibited the high-throughput performance necessary to screen current chemical space. Here, we describe a homogeneous assay to measure mitochondria membrane potential that can utilize either adherent or suspension cell types. The assay has been miniaturized to 1,536-well plate format, and was used to perform a fully automated robotic high-throughput screen of a small molecule chemical library.

Three tests were used to measure the circulating immunoglobulin in 381 purchased calves as they entered a commercial calf-rearing unit. A correlation of 0.64 was found between the zinc sulphate turbidity (ZST) test and a quantitative latex agglutination test (LAT) measuring IgG1 (P less than 0.001). A qualitative version of the LAT related poorly to the quantitative version. The proportion of plasma samples identified by the quantitative LAT as having an IgG1 concentration of less than 5 g/litre which were incorrectly identified as positives (greater than or equal to 5 g/litre) by the qualitative LAT was 0.65. The proportion of plasma samples identified by the quantitative LAT as having a IgG1 concentration of greater than or equal to 5 g/litre which were incorrectly identified as negative (less than 5 g/litre) was 0.11. There was no statistically significant relationship between plasma IgG1 concentration and initial liveweight, subsequent overall daily liveweight gain or disease incidence (P greater than 0.05). Calves treated for infectious disease, particularly respiratory disease after weaning, had statistically significantly lower liveweight gains than healthy calves (P less than 0.001).