Direct formation of thienopyridine-derived nitrosothiols--just add nitrite!

Thienopyridines (ticlopidine, clopidogrel and prasugrel) are pro-drugs that require metabolism to exhibit a critical thiol group in the active form that binds to the P2Y₁₂ receptor to inhibit platelet activation and prevent thrombus formation in vivo. We investigated whether these thienopyridines participate in S-nitrosation (SNO) reactions that might exhibit direct anti-platelet behaviour. Optimum conditions for in vitro formation of thienopyridine-SNO formation were studied by crushing ticlopidine, clopidogrel or prasugrel into aqueous solution and adding sodium nitrite, or albumin-SNO.

Direct vasoactive properties of thienopyridine-derived nitrosothiols.

Thienopyridines (ticlopidine, clopidogrel, and prasugrel) require in vivo metabolism to exhibit a critical thiol group in the active form that binds to the P2Y12 platelet receptor to inhibit platelet activation. We hypothesized that formation of thienopyridine-derived nitrosothiols (ticlopidine-SNO, clopidogrel-SNO, and prasugrel-SNO) occurs directly from the respective parent drug. Pharmaceutical-grade thienopyridine (ticlopidine, clopidogrel chloride, clopidogrel sulfate, clopidogrel besylate, or prasugrel) was added to nitrite in aqueous solution to form the respective thienopyridine-SNO (Th-SNO).

Conservative management of postoperatively diagnosed cystotomy.

Bladder injury is a common complication of hysterectomy that is often not recognized at the initial surgery. The conventional approach to intraperitoneal cystotomy is surgical repair. The goal of this case series was to introduce an alternative conservative treatment of posthysterectomy cystotomy.

Comparison of autologous rectus fascia and cadaveric fascia in pubovaginal sling continence outcomes.

Objective: The purpose of this study was to compare autologous versus cadaveric grafts in pubovaginal slings.

Study Design: Women who had pubovaginal slings from 1994 to 2003 completed history, questionnaires, prolapse staging, and cough stress testing. Failure was defined by recurrent urinary incontinence symptoms and reoperation for stress incontinence.