Citations

ABSTRACT Introduction Premature ejaculation (PE) and its individual and relationship consequences have been recognized in the literature for centuries. PE is one of the most common male sexual dysfunctions, affecting nearly one in three men worldwide between the ages of 18 and 59 years. Until recently, PE was believed to be a learned behavior predominantly managed with psychosexual therapy; however, the past few decades have seen significant advances in understanding its etiology, diagnosis, and management. There is, as yet, no one universally agreed upon definition of PE. Aim To review five currently published definitions of PE. Methods The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24–26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. Main Outcome Measure Data were utilized from the World Health Organization, the American Psychiatric Association, the European Association of Urology, the Second International Consultation on Sexual Dysfunctions, and the American Urological Association. Results The current published definitions of PE have many similarities; however, none of these provide a specific “time to ejaculation,” in part because of the absence of normative data on this subject. While investigators agree that men with PE have a shortened intravaginal ejaculatory latency time (IELT; i.e., time from vaginal penetration to ejaculation), there is now a greater appreciation of PE as a multidimensional dysfunction encompassing several components, including time and subjective parameters such as “control,”“satisfaction,” and “distress.” Conclusion There is a recent paradigm shift away from PE as a unidimensional disorder of IELT toward a multidimensional description of PE as a biologic dysfunction with psychosocial components.

Abstract Centrin is an evolutionarily conserved 20 kDa, Ca+2-binding, calmodulin-related protein associated with centrioles and basal bodies of phylogenetically diverse eukaryotic cells. Earlier studies have shown that residual centrosomes of non-rodent mammalian spermatozoa retain centrin and, in theory, could contribute this protein for the reconstruction of the zygotic centrosome after fertilization. The present work shows that CEN2 and CEN3 mRNA were detected in germinal vesicle-stage (GV) oocytes, MII oocytes, and pre-implantation embryos from the two-cell through the blastocyst stage, but not in spermatozoa. Boar ejaculated spermatozoa possess centrin as revealed by immunofluorescence microscopy and western blotting. Immature, GV oocytes possess speckles of centrin particles in the perinuclear area, visualized by immunofluorescence microscopy and exhibit a 19 kDa band revealed by western blotting. Mature MII stage oocytes lacked centrin that could be detected by immunofluorescence or western blotting. The sperm centrin was lost in zygotes after in vitro fertilization. It was not detectable in embryos by immunofluorescence microscopy until the late blastocyst stage. Embryonic centrin first appeared as fine speckles in the perinuclear area of some interphase blastocyst cells and as putative centrosomes of the spindle poles of dividing cells. The cells of the hatched blastocysts developed centrin spots comparable with those of the cultured cells. Some blastomeres displayed undefined curved plate-like centrin-labeled structures. Anti-centrin antibody labeled interphase centrosomes of cultured pig embryonic fibroblast cells as distinct spots in the juxtanuclear area. Enucleated pig oocytes reconstructed by electrofusion with pig fibroblasts displayed centrin of the donor cell during the early stages of nuclear decondensation but became undetectable in the late pronuclear or cleavage stages. These observations suggest that porcine zygotes and pre-blastocyst embryonic cells lack centrin and do not retain exogenously incorporated centrin. The early embryonic centrosomes function without centrin. Centrin in the blastocyst stage embryos is likely a result of de novo synthesis at the onset of differentiation of the pluripotent blastomeres.

Diabetic vascular dysfunction is associated with an increase in reactive oxygen species (ROS). In this study, we hypothesized that hyperglycemia-induced ROS generation would impair the function of large conductance Ca 2+ -activated K + (BK) channels, which are major determinants in vasorelaxation. We found that when cultured in high glucose (HG) (22 mmol/L), HEK293 cells showed a reduction in expressed hSlo current densities, as well as slowed activation and deactivation kinetics. When human coronary smooth muscle cells were cultured in HG, similar findings were observed for the BK currents. HG enhanced superoxide dismutase and suppressed catalase (CAT) expression in HEK293 cells, leading to a significant increase in intracellular ROS. The effects of HG were mimicked by hydrogen peroxide (H 2 O 2 ), and hSlo functions were restored by CAT gene transfer. Peroxynitrite inhibited hSlo current density but did not change channel kinetics. The hSloC911A mutant was insensitive to the effects of HG and H 2 O 2 . Hence, imbalance of antioxidant enzymes plays a critical role in ROS generation in HG, impairing hSlo functions through H 2 O 2 -dependent oxidation at cysteine 911. This may represent an important fundamental mechanism that contributes to the impairment of vasodilation in diabetes.