Ihog and Boi elicit Hh signaling via Ptc but do not aid Ptc in sequestering the Hh ligand.

Hedgehog (Hh) proteins are secreted molecules essential for tissue development in vertebrates and invertebrates. Hh reception via the 12-pass transmembrane protein Patched (Ptc) elicits intracellular signaling through Smoothened (Smo). Hh binding to Ptc is also proposed to sequester the ligand, limiting its spatial range of activity. In Drosophila, Interference hedgehog (Ihog) and Brother of ihog (Boi) are two conserved and redundant transmembrane proteins that are essential for Hh pathway activation. How Ihog and Boi activate signaling in response to Hh remains unknown; each can bind both Hh and Ptc and so it has been proposed that they are essential for both Hh reception and sequestration. Using genetic epistasis we established here that Ihog and Boi, and their orthologs in mice, act upstream or at the level of Ptc to allow Hh signal transduction. In the Drosophila developing wing model we found that it is through Hh pathway activation that Ihog and Boi maintain the boundary between the anterior and posterior compartments. We dissociated the contributions of Ptc from those of Ihog/Boi and, surprisingly, found that cells expressing Ptc can retain and sequester the Hh ligand without Ihog and Boi, but that Ihog and Boi cannot do so without Ptc. Together, these results reinforce the central role for Ptc in Hh binding in vivo and demonstrate that, although Ihog and Boi are dispensable for Hh sequestration, they are essential for pathway activation because they allow Hh to inhibit Ptc and thereby relieve its repression of Smo.

Clinical effect of doxazosin combined with diclofenac sodium in the treatment of bladder spasm after transurethral bipolar plasmakinetic prostatectomy / 中华老年医学杂志

Objective To observe the clinical effect of doxazosin combined with diclofenac sodium in the treatment of bladder spasm after transurethral bipolar plasmakinetic prostatectomy (TUPKP).Methods 200 BPH patients undergoing TUPKP were randomly divided into 4 groups according to single-blind randomized controlled trial design:group A,group B,group C,group D (n =50,each).Patients in group A were given diclofenac sodium 100 mg,q12h,in anus after surgery and doxazosin 4 mg/d orally after anesthetic awareness.Patients in group B were given diclofenac sodium in anus 100 mg,q 12h in anus after surgery.Patients in group C were given doxazosin 4 mg/d orally after anesthetic awareness.Patients in group D were not given diclofenac sodium and doxazosin.Drugs were withdrawn 3 days after surgery.Results In group A,the average time of bladder spasm was (0.47±0.18) time,(0.35±0.16) time,(0.30±0.20) time at the 1st,2 nd,3 rd day respectively; the duration of bladder spasm was (3.2±1.5) min,(2.1±1.3) min,(1.4±1.2)min at the 1st,2nd,3th day respectively; the time of bladder perfusion clearance was (1.5± 0.3)days and the time of urethral catheter removal was (4.0±0.5) days.There were significant differences in above observed values between group D and the other groups (all P＜0.05).Conclusions Doxazosin combined with diclofenac sodium therapy is effective in the treatment of bladder spasm after bipolar transurethral plasmakinetic prostatectomy.