http://repub.eur.nl/res/aut/10818/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/9369/ 2000-01-01T00:00:00Z Heated (20 min at 70 degrees C) amphotericin B-desoxycholate (hAMB-DOC) was further characterized, as was another formulation obtained after centrifugation (60 min, 3000 x g), hcAMB-DOC. Conventional AMB-DOC consisted of individual micelles (approximately 4 nm in diameter) and threadlike aggregated micelles, as revealed by cryo-transmission electron microscopy. For both hAMB-DOC and hcAMB-DOC, pleiomorphic cobweb structures were observed with a mean particle size of approximately 300 nm as determined by laser diffraction. The potent antifungal activity of AMB-DOC against Candida albicans is not reduced by heating. Effective killing of C. albicans (>99.9% within 6 h) was obtained at 0.1 mg/liter with each of the AMB formulations. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release ((86)Rb(+)) from C. albicans of > or =50% was observed at 0.8, 0.4, and 0.4 mg/liter, respectively. After heating of AMB-DOC, toxicity was reduced 16-fold as determined by red blood cell (RBC) lysis. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, hemolysis of > or =50% was observed at 6.4, 102.4, and 102.4 mg/liter, respectively. In contrast, AMB-DOC and its derivates showed similar toxicities in terms of cation release from RBC. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release ((86)Rb(+)) of > or =50% was observed at 1.6, 0.8, and 0.8 mg/liter, respectively. In persistently leukopenic mice with severe invasive candidiasis, higher dosages of both hAMB-DOC and hcAMB-DOC were tolerated than those of conventional AMB-DOC (3 versus 0.8 mg/kg of body weight, respectively), resulting in significantly improved therapeutic efficacy. In conclusion, this new approach of heating AMB-DOC may be of great value for further optimizing the treatment of severe fungal infections. http://repub.eur.nl/res/pub/25997/ 1977-01-19T00:00:00Z The testis contains two cell compartments respectively having an endocrine and an exocrine function. The seminiferous tubules contain a cell renewal system concerned with the production of spermatozoa, and are the exocrine part of the organ. In the other compartment, the interstitial tissue, Leydig cells are found having an endocrine function in the biosynthesis of androgenic steroids. The studies presented in this thesis are mainly concerned with two questions regarding the role of steroids in the testis: -Firstly, which (sub) cellular structures are involved in the synthesis and secretion of androgen in the Leydig cells. -Secondly, which testicular cells or cell organelles are targets for androgen and estrogen action and what" is the route by which these steroids reach their targets. To answer these questions tritiated steroids have been administered to the rat testis under various experimental conditions. The incorporated radioactivity was subsequently localized in tissue sections by autoradiography both at the level of the light and of the electron microscope. Before discussing the merits and the technical problems of this experimental approach an outline of the role of steroids (among other factors) in testis in general and for spermatogenesis in particular will be given.