Effect of autologous muscle-derived cells in the treatment of urinary incontinence in female patients with intrinsic sphincter deficiency and epispadias: A prospective study.

OBJECTIVES: To evaluate the effect of autologous muscle-derived cells injection in the treatment of complicated stress urinary incontinence in female patients. METHODS: Female patients presenting with severe and complicated stress urinary incontinence secondary to the bladder neck and/or urethral trauma or congenital epispadias (with or without exstrophy) were enrolled in this prospective study. They underwent transurethral injection of autologous muscle-derived cells. In selected cases, another injection was given after 6 months, as per the surgeon's assessment. All patients were monitored for 1 year, and the effect of autologous muscle-derived cells was evaluated by cough stress test, 1-h pad test and Incontinence Impact Questionnaire-short form score. A multichannel urodynamic study and maximum urethral closure pressure were carried out before and 12 months after the last treatment session. Cough stress test, 1-h pad test and uroflowmetry were repeated 36 months after the last injection. Severity and occurrence of complications were recorded at each visit. RESULTS: All 10 patients who completed the study were monitored for 36 months. Three patients were cured, four had improved and three did not respond to the treatment. There was no major adverse effect related to the treatment. CONCLUSIONS: Muscle-derived cell therapy might represent a minimally-invasive and a safe procedure in the treatment of patients with severe and complicated stress urinary incontinence.

Design, synthesis, and cytotoxicity evaluation of novel indole-acylhydrazone derivatives of 4-pyridinone as potential histone deacetylase-2 inhibitors.

Background and purpose: Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors. Experimental approach: Seven indole-acylhydrazone-pyridinone derivatives were synthesized via simple, straightforward chemical procedures. The molecular docking studies were accomplished on HDAC2 compared to panobinostat. The cytotoxicity of all derivatives was studied on MCF-7 and MDA-MB-231 breast cancer cell lines by MTT assay. Findings / Results: Molecular docking studies supported excellent fitting to the HADC2 active site with binding energies in the range of -10 Kcal/mol for all derivatives. All compounds were tested for their cytotoxicity against MCF-7 and MDA-MB-231 cell lines; derivatives A, B, F, and G were the best candidates. The half-maximal inhibitory concentration (IC50) values on MCF-7 were below 25 mg/mL and much lower than those obtained on the MDA-MB-231 cell line. Conclusion and implications: The derivatives showed selectivity toward the MCF-7 cell line, probably due to the higher HDAC expression in the MCF-7 cell line. In this regard, debenzylated derivatives F and G showed slightly better cytotoxicity, which should be more studied in the future. Derivatives A, B, F, and G were promising for future enzymatic studies.