In our cohort 24% of adult patients with spina bifida were sexually active. Sexual activity was not related to gender, level of urinary incontinence or extent of physical disability but it was more likely in patients with more caudal levels of neurological impairment. Sexual function seems not to affect health related quality of life in these patients.

Lassmann J, Sliwoski J, Chang A, Canning DA, Zderic SA. Deletion of one SERCA2 allele confers protection against bladder wall hypertrophy in a murine model of partial bladder outlet obstruction. Am J Physiol Regul Integr Comp Physiol 294: R58-R65, 2008. First published October 31, 2007 doi:10.1152/ajpregu.00477.2007.-The sarco(endo)plasmic reticulum Ca 2ϩ -ATPase2 (SERCA2) is downregulated in cardiac hypertrophy with decompensation. We sought to determine whether mice heterozygous for the SERCA2 allele would develop greater bladder hypertrophy and decompensation than their wild-type littermates following partial bladder outlet obstruction (pBOO). We found that following 4 wk of surgically created pBOO, SERCA2 heterozygous murine bladders showed significantly less hypertrophy, improved in vitro cystometry performance, diminished expression of the slow myosin isoform A analyzed by RT-PCR, a significant drop in nuclear translocation of nuclear factor of activated T cells by EMSA, and decreased cell proliferation within the smooth muscle layer following 5-bromo-2Ј-deoxyuridine labeling compared with their wild-type littermates. Thus, in contrast to cardiac muscle, deletion of a SERCA2 allele confers protection against bladder hypertrophy in a murine model of pBOO. Compensatory mechanisms in heterozygous mice seem to be related to the calcineurin pathway. Further studies are underway to better define the molecular basis of this observation, which has potential clinical applications. urinary bladder; obstruction; sarco(endo)plasmic reticulum Ca 2ϩ -ATPase2; nuclear factor of activated T cells INTRACELLULAR CA 2ϩ LEVELS are tightly regulated by a series of channels or ATP-dependent pumps that allow for transport across the plasma membrane or intracellular organelles such as the sarcoplasmic reticulum. This machinery has evolved in all cells given the key role of Ca 2ϩ as a ubiquitous second messenger but assumes extra importance in muscle where Ca 2ϩ release triggers contraction and sequestration is required for relaxation. Three categories of ion-transport ATPases transfer Ca 2ϩ out of the cytosol and play a critical role in its homeostasis: the secretory pathway Ca 2ϩ -ATPase (SPCA), the sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA), and the plasma membrane Ca 2ϩ -ATPase (PMCA) (28). Three SERCA isoforms are expressed in mammalian tissues (6,7,16,21). SERCA1 is expressed in fast-twitch skeletal muscle (26). SERCA2-ATPases exist in three different isoforms: SERCA2a and SERCA2c are the Ca 2ϩ -ATPases of cardiac and slowtwitch skeletal muscle (13, 21), whereas SERCA2b is expressed in all tissues including heart and smooth muscle (17). SERCA3 can be found in different nonmuscle tissues as vascular and tracheal epithelium and pancreatic ␤-cells (1, 2). Similar molecular mechanisms are involved in cardiac and bladder smooth muscle in response to mechanical stimuli and the subsequent development of hypertrophy and decompensation (10, 31). One pathway that has received attention in both organ systems is the calcine...

Introduction Vaginal atrophy is a consequence of menopause however little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis. Aim The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause. Methods 3–4 month old Sprague Dawley rats underwent sham laparotomy (Sham, n=18) or ovariectomy (Ovx, n=39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17- β estradiol (Ovx). Animals were euthanized one week later and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way ANOVA followed by Tukey's post hoc analysis (α= 0.05). Main Outcome Measures Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractility Results Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform SM1 and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino terminal MHC isoforms, l-caldesmon expression and maximal velocity of shortening. Conclusion Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated with changes in the vaginal muscularis, which may contribute to the increased incidence of pelvic floor disorders with age.

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We hypothesized that the calcineurin-nuclear factor of activated T-cells (NFAT) pathway is activated following partial bladder outlet obstruction (pBOO), which would allow for pharmacologic treatment to prevent the ensuing bladder wall hypertrophy. Using a model of pBOO in male mice, we were able to demonstrate increased nuclear importation of the transcription factors NFAT and myocyte enhanching factor 2 both of which are under control of calcineurin in both the whole bladder wall as well as the urothelium. We further confirmed that this pathway was activated using transgenic mice containing an NFAT-luciferase reporter construct. Mice were randomized following pBOO to treatment with or without cyclosporine A (CsA), a known inhibitor of calcineurin. The bladder-to-body mass ratio (mg bladder wt/g body wt) of 0.95 ± 0.03 in shams increased to 3.1 ± 0.35 following pBOO, and it dropped back to 1.7 ± 0.22 in the CsA+ group (P < 0.001). Luciferase values (RLU) of 1,130 ± 133 in shams increased to 2,010 ± 474 following pBOO and were suppressed to 562 ± 177 in the CsA+ group (P < 0.05). The myosin heavy chain mRNA (A/B) isoform ratio of 0.07 ± 0.03 in shams increased to 1.04 ± 0.19 following pBOO but it diminished to 0.24 ± 0.1 in the CsA+ group (P < 0.001). In vitro whole organ physiology studies demonstrated improved responses in those bladders from mice treated with CsA. The mRNAs for all four known calcineurin-responsive NFAT isoforms are expressed in the bladder wall, although NFATc(3) and NFATc(4) predominate. Both NFATc3 and NFATc4 are expressed in urothelial as well as smooth muscle cells. We conclude that pBOO activates the calcineurin-NFAT pathway and that CsA treatment decreased bladder hypertrophy, shifted the pattern of myosin isoform mRNA expression back toward that seen in normal controls, and resulted in improved in vitro whole organ performance.