A method is described for the determination of urea in plasma and urine. The effects of variations in the experimental conditions are examined and the results of recovery experiments and other tests of precision and accuracy are reported.In comparison with other methods in current use, this method has distinct advantages in sensitivity, simplicity, and precision, thus economizing in time, sample volume, reagents, and equipment.Although urea in biological fluids is frequently measured, a method has yet to be described which is precise, sensitive, and simple. Those most commonly used depend on the measurement of ammonium carbonate produced by hydrolysis with urease, or on the measurement of the yellow pigment formed by condensing diacetyl with urea. The best results are obtained by urease hydrolysis followed by aeration and titration of ammonia, but this requires large samples and is time consuming.

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11–induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.

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