ABSTRACT
RGD-peptides can inhibit the binding of ligands to certain beta3 integrins, alphaIIbbeta3 and alphavbeta3, both of which are involved in neointimal hyperplasia that contributes to atherosclerosis and restenosis of arterial walls. Saxatilin, a disintegrin from a Korean snake (Gloydius saxatilis), interacts with integrins alphaIIbbeta3 and alphavbeta3. It suppressed the adhesion of human coronary artery smooth muscle cells (HCASMCs) to vitronectin with an IC(50) of 2.5 microM, and growth factor (PDGF-BB or bFGF)-induced proliferation was inhibited at an IC(50) of 25 microM. Saxatilin disassembled the actin cytoskeleton of focal adhesion and induced cell detachment. This disassembly of focal adhesion in saxatilin-treated HCASMCs involved caspase-induced paxillin degradation. Saxatilin temporally phosphorylated FAK and ERKs and affected the cell cycle of HCASMCs by increasing CDK inhibitors (p21 and p27) and reducing cyclins (D1/2 and E). These results may have significant implications for integrin antagonistic therapy used for the treatment of atherosclerosis and restenosis.
Subject(s)
Disintegrins/pharmacology , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/drug effects , Viperidae/physiology , Animals , Cell Adhesion/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases/metabolism , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Humans , Snake Venoms/chemistryABSTRACT
BACKGROUND: To evaluate the efficacy of EMG biofeedback and pelvic floor electrical stimulation in the stress urinary incontinence patients by Kontinence HMT2000. MATERIALS AND METHODS: A group of 14 patients with stress urinary incontinence were treated with combined biofeedback and intravaginal electrical stimulation during 12 sessions from 2 weeks to 6 weeks. RESULTS: At immediate post treatment, subjective cure rate was 28% and improvement rate was 57% and failure rate was 15%. Thus the overall success rate for this treatment was 85%. The result of 3 months after treatment showed cure rate 14% and improvement rate was 43%. Intravaginal pressure increased by an average of 11.9 cmH2O. Increased vaginal pressure was found in 93% of the patients and more than 50% increment of intravaginal pressure was 71%. CONCLUSIONS: Combined biofeedback and pelvic floor electrical stimulation by use of Kontinence HMT2000 is effective for the patients who have good compliance, relative low degree stress urinary incontinence. In order to attain good results, a well structured program that teaches specific muscle exercise and the patients should be followed by regular interval reinforcement treatment.
