Blood changes and fertility derangements following the injection of Candida albicans into the spleen of the experimental animals (occurrence of hypersplenism)

Summary The injection ofCandida albicans (under experimental conditions used here) into the spleens of Wistar rats and Swiss mice produces profound hematological changes which are similar in rats and mice. After injection of the organisms there was steady lowering of the white cells and of the platelets in mice and in rats. Following splenectomy there was a sharp rise of both platelets and white cells in mice and rats. Mild normocytic, normochromic anemia was observed during the experiment. Following the splenectomy the level of hemoglobin returned to normal in fourteen weeks in the rats and in thirteen weeks in the mice. An increased level of reticulocytes and siderocytes was observed during the experiment. The mean value of the spleen weights in the experimental animals was higher than in the controls. Hyperplasia was the constant histological feature of these spleens. Bone marrow was either normal or hyperplastic. plastic. These changes correspond to the picture known in human pathology as hypersplenism. The injected organisms could still be cultured from the spleen about 4–6 months after operation. Attempts to isolate the injected organisms after 6 months were unsuccessful. The experimental mice showed derangement of fertility. Of the forty females mated with normal males only seven became pregnant. The litters were normal, 7–12 babies. Thirty percent of the young died before one month. Many of them showed growth retardation.This work was supported by a Damon Runyon Memorial Fund Grant No. 720.     

Nonpeptide HIV protease inhibitors designed to replace a bound water

Cyclic nonpeptide molecules were designed and synthesized with the goal of displacing the conserved flap-associated water of HIV-1 protease. Several such molecules were competitive inhibitors with micromolar inhibition constants, and their structure-activity relationships were consistent with the design hypothesis.