Modified Circumcision Using the Disposable Circumcision Suture Device in Children: A Randomized Controlled Trial.

OBJECTIVE: To evaluate and compare the surgical outcomes and complications of the modified circumcision using disposable circumcision suture device (device group) and the conventional dorsal slit circumcision (conventional group) in children. METHODS: A total of 284 patients were randomized to either device group or conventional group. All patients were preoperatively assessed and evaluated at 4 weeks after surgery. The perioperative data and postoperative outcomes were compared between the 2 groups. RESULTS: No statistical differences were observed in the average age and indications between the 2 groups preoperatively (P > .05). Compared with the conventional group, patients in the device group were shorter mean operative time, less blood loss, lower intraoperative and postoperative pain score, faster incision healing time and a higher satisfaction rate of penile cosmetic appearance (P < .01). Similarly, the incidences of complication were significantly lower in the device group than in the conventional group (4.3% vs 12.3%, P < .05). CONCLUSIONS: The modified circumcision using disposable circumcision suture device is a simple, safe, faster, and effective procedure and may become the attractive alternative to the conventional technique for the children, with a relatively lower complication rate and better cosmetic results. With the improvement of disposable circumcision suture device, the modified circumcision using disposable circumcision suture device has the potential to be widely used in the world.

Optimization of taxane binding to microtubules: binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel.

The microtubule binding affinities of a series of synthetic taxanes have been measured with the aims of dissecting individual group contributions and obtaining a rationale for the design of novel compounds with the ability to overcome drug resistance. As previously observed for epothilones, the positive and negative contributions of the different substituents to the binding free energies are cumulative. By combining the most favorable substitutions we increased the binding affinity of paclitaxel 500-fold. Insight into the structural basis for this improvement was gained with molecular modeling and NMR data obtained for microtubule-bound docetaxel. Taxanes with affinities for microtubules well above their affinities for P-glycoprotein are shown not to be affected by multidrug resistance. This finding strongly indicates that optimization of the ligand-target interaction is a good strategy to overcome multidrug resistance mediated by efflux pumps.

Restoration of Microtubule Interaction and Cytotoxicity in D-seco Taxanes upon Incorporation of 20-Hydroxymethyl-4-allyloxy Groups.

To probe the exact role of the oxetane D ring in both tubulin binding and cytotoxicity of taxanes, novel D-seco taxanes bearing a C4 ether substituent have been prepared from paclitaxel 1a. Among them, 20-hydroxymethyl-4-allyloxy D-seco taxane 5e is the most active in both tubulin and cytotoxicity assays. It is only slightly less potent than 1a on tubulin polymerization promotion in vitro and the most cytotoxic among all D-seco taxanes known to date. The reason for the loss and restoration of bioactivity for these D-seco taxanes is also discussed with the assistance of NMR and molecular modeling studies. From these results, we draw a conclusion that the intact D ring of taxanes is not strictly necessary for their binding to tubulin and cytotoxic effects.

Synthesis, biological evaluations, and tubulin binding poses of C-2alpha sulfur linked taxol analogues.

In combination with chemical modifications, bioassays, and computational simulation techniques, C-2 benzoylthio, and benzylthio taxoids were synthesized, biologically evaluated, and their binding conformations rationalized, in order to probe the interaction of taxane molecule with beta-tubulin.

Overcoming tumor drug resistance with high-affinity taxanes: a SAR study of C2-modified 7-acyl-10-deacetyl cephalomannines.

A series of C2-modified 10-deacetyl-7-propionyl cephalomannine derivatives was designed, prepared, and biologically evaluated. Some C2 meta-substituted benzoate analogues showed potent activity against both drug-sensitive and drug-resistant tumor cells in which resistance is mediated through either P-gp overexpression or beta-tubulin mutation mechanisms. The taxoid 15 b and related compounds are of particular interest, as they are much more cytotoxic than paclitaxel, especially against drug-resistant tumor cells; they are able to kill both drug-resistant and drug-sensitive cells (low R/S ratio), and they have high affinity for beta-tubulin. Our research results led to an important hypothesis, that is, a taxane with very high binding affinity for beta-tubulin is able to counteract drug resistance, which may assist in future taxane-based drug-discovery efforts.