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Fifty-one leprosy patients receiving long-term clofazimine have undergone systematic clinical laboratory testing in a search for any toxicity secondary to the drug. In approximately 220 patient-years of observation and in analyzing approximately 40,000 test results, no statistically significant changes in the direction of abnormality have been observed in SGOT, thymol turbidity, serum globulins, uric acid, alkaline phosphatase, white blood cell count or differential, hematocrit, hemoglobin, BUN, serum creatinine, serum cholesterol, serum albumin, serum potassium, serum calcium, stool for occult blood, routine urinalysis, or reticulocyte count. Statistically significant changes toward abnormality were found in fasting blood sugar and total serum bilirubin. These statistically significant changes in the direction of abnormality were of a small magnitude, were not associated with related clinical signs or symptoms, and do not seem to be of major clinical significance. Despite the accumulation of relatively massive amounts of the drug in various tissues, clofazimine appears remarkably free of serious or life-threatening toxicity clinically. Although the skin and gastrointestinal side effects of clofazimine limit its usefulness, on the evidence to date, its advantages outweigh its disadvantages in those leprosy patients for whom it is indicated.

A highly specific, high affinity binding protein for estradiol-17beta (E2) is present in cytosol prepared from the epididymides of immature (21-53 day old) rabbits. This binding moiety sediments on sucrose gradients as an 8S species under low ionic strength conditions and as a 4S species under conditions of high ionic strength (0.3 M KCL). The relative binding affinities of estrogens for the binding protein was E2 is greater than estrone is greater than estriol. Neither 5alpha-dihydrostestosterone (5alphaKHT), progesterone, nor cortisol were able to inhibit binding of [3H]E2 to epididymal binding sites. An 8S binding moiety for E2 was present in testicular cytosol but not in muscle. An apparently non-specific binding component for E2 was present in plasma which sedimented in the 4S region of low ionic strength gradients. The epididymal E2 binding moiety was distinct from a 4S androen binding protein of testicular origin which is detectable in cytosol prepared from epididymides of rabbits at certain stages development. We were unalbe to detect a specific E2 binding protein in epididymal cytosol from mature intact or 4-day castrated rabbits. The E2 binding component in the cytosol of immature rabbits had an Kd congruent to 2-10 X 10-10 M and the concentration of binding sites was in the order of 1-4 X 10-13 mmoles/mg of protein. The binding component was thermo-labele and pronase, but not nuclease, sensitive.