Using a new experimental model for studying the hormonal induction of spermatogenesis, the hpg mouse, which has congenital functional gonadotropin deficiency due to a major deletion in the GnRH gene, we investigated the roles of testosterone (T) and dihydrotestosterone (DHT) in the initiation of spermatogenesis. Weanling homozygous hpg male mice were implanted subdermally with SILASTIC brand implants of varying lengths (0-2 cm) filled with T or DHT, using phenotypically normal (N/N or N/hpg) and untreated hpg/hpg mice as positive and negative controls. After 8 weeks, both T and DHT equally stimulated (approximately 14-fold) testis size and induced qualitatively complete spermatogenesis despite low intratesticular androgen levels and undetectable circulating FSH. Stereological quantitation of Sertoli and germ cells demonstrated a dose-dependent rise in the absolute numbers of all germ cell types induced by both T and DHT. At maximal androgen doses, germ cell numbers expressed per Sertoli cell and homogenization-resistant elongated spermatids expressed per mg testis were increased to more than 80% of non-hpg control values. An in vitro fertilization assay confirmed that both T and DHT induced quantitatively normal fertilizing capacity of the sperm in hpg males. We conclude that androgens, acting through the androgen receptor without need for aromatization, initiate qualitatively complete spermatogenesis in the mouse, including fertile sperm despite low intratesticular androgen levels and the absence of blood FSH levels. The hpg mouse model is a useful new paradigm to study the molecular basis of the hormonal induction of spermatogenesis.
Mortality from prostate cancer is associated with progression of tumors to androgen-independent growth and metastasis. Eicosanoid products of both the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumor vascularization and metastasis in animal models. Pharmacologic agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Phospholipase A 2 (PLA 2 ) enzymes regulate the provision of arachidonic acid to both COX-and LOX-derived eicosanoids, and a secreted form of the enzyme (sPLA 2 -IIA) is elevated in prostate cancer tissues. Here, we show by immunohistochemistry, in patients receiving androgen ablation therapy, that sPLA 2 -IIA remains elevated in remaining cancer cells relative to benign glands after treatment. Furthermore, sPLA 2 -IIA expression seen in benign glands is substantially decreased after androgen depletion, whereas cytosolic PLA 2 -␣ (cPLA 2 -␣) levels are unchanged. sPLA 2 -IIA mRNA expression is detectable and inducible by androgen (0.01-10 nmol
Background: National joint replacement registries outside North America have been effective in reducing revision risk. However, there is little information on the role of smaller regional registries similar to those found in Canada or the United States. We sought to understand trends in total hip (THA) and knee (TKA) arthroplasty revision patterns after implementation of a regional registry. Methods:We reviewed our regional joint replacement registry containing all 30 252 cases of primary and revision THA and TKA performed between Jan. 1, 2005, and Dec. 31, 2013. Each revision case was stratified into early (< 2 yr), mid (2-10 yr) or late (> 10 yr), and we determined the primary reason for revision. Results:The early revision rate for TKA dropped from 3.0% in 2005 to 1.3% in 2011 (R 2 = 0.84, p = 0.003). Similarly, the early revision rate for THA dropped from 4.2% to 2.1% (R 2 = 0.78, p = 0.008). Despite primary TKA and THA volumes increasing by 35.5% and 39.5%, respectively, there was no concomitant rise in revision volumes. The leading reasons for TKA revision were infection, instability, aseptic loosening and stiffness. The leading reasons for THA revision were infection, instability, aseptic loosening and periprosthetic fracture. There were no discernible trends over time in reasons for early, mid-term or late revision for either TKA or THA. Conclusion:After implementation of a regional joint replacement registry we observed a significant reduction in early revision rates. Further work investigating the mechanism by which registry reporting reduces early revision risk is warranted.Contexte : Ailleurs qu'en Amérique du Nord, les registres nationaux des remplacements articulaires ont été efficaces pour réduire le risque de révision. Cependant, il y a peu d'information sur le rôle des plus petits registres régionaux comme ceux qu'on trouve au Canada et aux États-Unis. Nous avons donc cherché à comprendre les tendances en matière de révision des arthroplasties totales de la hanche (ATH) et du genou (ATG) après la création d'un registre régional.
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