Nerve stimulator-guided pudendal nerve block vs general anesthesia for postoperative pain management after anterior and posterior vaginal wall repair: a prospective randomized trial.

STUDY OBJECTIVE: Compare the effectiveness of nerve stimulator-guided pudendal nerve block (PNB) vs general anesthesia (GA) for anterior and posterior (AP) colporrhaphy in terms of pain relief and analgesic consumption within 24 and 48 hours postoperatively. DESIGN: Prospective randomized trial. PATIENTS: Fifty-seven patients whose ages ranged between 20 and 53 years scheduled to undergo AP colporrhaphy due to the presence of cystorectocele. INTERVENTIONS: Patients were randomly assigned into 2 groups receiving either nerve stimulator-guided PNB (n = 28) or GA (n = 29). A total volume of 0.7 mL/kg of the local anesthetic mixture was injected at 4 sites. MAIN RESULTS: Both groups were similar with respect to age, weight, height, and surgery duration. There was a significant difference in average pain scores within the first and second postoperative days (P values = .005 and .004, respectively). Total analgesic consumption (ketoprofen and tramadol) was significantly lower in the PNB within the first (P values = .018 and .010) and second postoperative days (P values = .041 and .011), respectively. Return to normal daily activity was significantly (P< .0001) shorter in the PNB group compared with the GA group (3.6 days vs 12.2 days). A total of 71.4% of the patients in the PNB group were satisfied compared with 27.8% in the GA group (P< .0001). Surgeon satisfaction was significantly higher in the PNB group (82.1% vs 34.5%, P< .0001). CONCLUSION: This randomized controlled trial demonstrated that nerve stimulator-guided PNB could be used as an alternative to GA for AP repair of stages I and II prolapse because it is associated with less postoperative pain and analgesic consumption, in addition to shorter duration of recovery.

Bioinspired Syntheses of the Pyridoacridine Marine Alkaloids Demethyldeoxyamphimedine, Deoxyamphimedine, and Amphimedine.

Efficient bioinspired syntheses of the biologically active pyridoacridine marine alkaloids demethyldeoxyamphimedine, deoxyamphimedine, and amphimedine are reported. Reaction of styelsamine D, prepared via an optimized route starting from Boc-dopamine, with paraformaldehyde afforded demethyldeoxyamphimedine and deoxyamphimedine. Oxidation of the latter using either K3[Fe(CN)6] or DMSO/conc. HCl gave amphimedine in 8 steps from tryptamine with an overall yield of 14%. The versatility of the method was demonstrated by the synthesis of non-natural ethyl and benzyl congeners of deoxyamphimedine and amphimedine.

Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B.

In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds.

Biomimetic synthesis of thiaplidiaquinones A and B.

A biomimetic synthesis of the biologically active ascidian metabolites thiaplidiaquinones A and B is described. Reaction of geranylbenzoquinone with Et(3)N in CH(2)Cl(2) yielded two isomeric quinones, comprising the benzo[c]chromene-7,10-dione core of the natural products. Subsequent reaction with hypotaurine yielded the title compounds and their dioxothiazino regioisomers.