Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 µg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

Partial stapled hemorrhoidopexy versus circular stapled hemorrhoidopexy for grade III-IV prolapsing hemorrhoids: a two-year prospective controlled study.

BACKGROUND: Circular stapled hemorrhoidopexy (CSH) is an effective technique for treating prolapsing hemorrhoids; but urgency and anal stenosis are common postoperative complications. The aim of this study was to assess the efficacy and postoperative outcomes of partial stapled hemorrhoidopexy (PSH), compared with CSH. METHODS: Seventy-two consecutive patients with grade III and IV hemorrhoids who met the inclusion/exclusion criteria were divided in a non-randomized manner to undergo either PSH (n = 34) or CSH (n = 38). Intraoperative and postoperative parameters in both groups were collected and compared. RESULTS: The postoperative visual analog score for pain at first defecation was significantly lower in the PSH group than that in the CSH group (P = 0.001). Fewer patients in the PSH group experienced postoperative urgency, compared with those in the CSH group at 12 h, 1 day, and 7 days after surgery (P = 0.025, P = 0.019, and P = 0.043, respectively). Gas incontinence occurred in 3 patients (7.9%) in the CSH group, but in none of patients in the PSH group (P = 0.242). Postoperative anal stenosis developed in one patient (2.6%) in the CSH group, but in none of the patients in the PSH group (P = 1.0). The 2-year recurrence rate was 2.9 and 5.3%, respectively, in the PSH and CSH groups (P = 1.0). CONCLUSIONS: The 2-year recurrence rate is similar in patients with grade III-IV hemorrhoids treated with PSH or CSH. However, PSH is associated with less postoperative pain, fewer episodes of urgency, and no anal incontinence or anal stenosis.