By Michael Zinner, Jr, Stanley Ashley
Univ. of Louisville, KY. reports the pathophysiology and therapy of such a lot factors of male hypogonadism and summarizes contemporary examine. Explores the newest puzzling over the motives of gonadotropin deficiency and testicular failure and discusses the effect of getting older and ailment on pituitary-testicular functionality. DNLM: Hypogonadism.
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Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem Res Toxicol 2004; 17(1):3–16. 63. Qiu Y, Benet LZ, Burlingame AL. Identiﬁcation of the hepatic protein targets of reactive metabolites of acetaminophenin in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J Biol Chem 1998; 273(28):17940–53. 64. Nelson SD, Dahlin DC, Rauckman EJ, et al. Peroxidase-mediated formation of reactive metabolites of acetaminophen.
Iyer R, Coles B, Raney KD, et al. DNA adduction by the potent carcinogen aﬂatoxin B1: mechanistic studies. J Am Chem Soc 1994; 116(5):1603–9. 68. Johnson WW, Guengerich FP. Reaction of aﬂatoxin B1 exo-8,9-epoxide with DNA: kinetic analysis of covalent binding and DNA-induced hydrolysis. Proc Natl Acad Sci USA 1997; 94(12):6121–5. 69. Johnson WW, Ueng Y-F, Mannervik B, et al. Conjugation of highly reactive aﬂatoxin B1 8,9-exoepoxide catalyzed by rat and human glutathione transferases: estimation of kinetic parameters.
This aspect can be done without radiolabeled material. Quantitation of in vivo (animal) results is done subsequently, with radiolabeled drug. A rough decision cutoff value of 50 pmol adduct/mg protein has been proposed (62), but obviously this value would be a function of dose, time, etc. The overall plan in these strategies is to ﬁnd better and earlier biomarkers that can be used effectively in the development process and even in clinical trials and marketed drugs. A critical issue with candidates found in animals is extrapolation to humans.