ABSTRACT
Fibroepithelial polyp of the ureter is a benign tumor of mesodermal origin that rarely occurs in children. The most common presenting symptoms are hematuria and flank pain by obstruction of the urinary tract. The etiology of this tumor is still not clear. It occurs more frequently in boys and often arises in the proximal ureter and the ureteropelvic junction. The preoperative diagnosis is difficult. We present here the case of a 11-year-old boy who had fibroepithelial polyps as the cause of the left flank ureteropelvic junction obstruction at pyeloplasty, and had the same condition on the right flank 5 years ago. We used polypectomy and pyeloureterostomy to treat the boy. No major intraoperative or preoperative complications developed.
Subject(s)
Neoplasms, Fibroepithelial/diagnosis , Polyps/diagnosis , Ureteral Neoplasms/diagnosis , Child , Humans , Male , Neoplasms, Fibroepithelial/pathology , Neoplasms, Fibroepithelial/surgery , Polyps/pathology , Polyps/surgery , Ureteral Neoplasms/pathology , Ureteral Neoplasms/surgery , Urologic Surgical Procedures/methodsABSTRACT
1. Deletion of phenylalanine at position 508 (DeltaF508) of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the most common mutation causing cystic fibrosis (CF). Effective pharmacological therapy of CF caused by the DeltaF508-CFTR mutation requires the rescue of both intracellular processing and channel gating defects. 2. We identified a class of natural coumarin compounds that can correct the defective DeltaF508-CFTR chloride channel gating by screening a collection of 386 single natural compounds from Chinese medicinal herbs. Screening was performed with an iodide influx assay in Fischer rat thyroid epithelial cells coexpressing DeltaF508-CFTR and an iodide-sensitive fluorescent indicator (YFP-H148Q/I152L). 3. Dose-dependent potentiation of defective DeltaF508-CFTR chloride channel gating by five coumarin compounds was demonstrated by the fluorescent iodide influx assay and confirmed by an Ussing chamber short-circuit current assay. Activation was fully abolished by the specific CFTR inhibitor CFTR(inh)-172. Two potent compounds, namely imperatorin and osthole, have activation K(d) values of approximately 10 micromol/L, as determined by the short-circuit current assay. The active coumarin compounds do not elevate intracellular cAMP levels. Activation of DeltaF508-CFTR by the coumarin compounds requires cAMP agonist, suggesting direct interaction with the mutant CFTR molecule. Kinetics analysis indicated rapid activation of DeltaF508-CFTR by the coumarin compounds, with half-maximal activation of < 5 min. The activating effect was fully reversed for all five active compounds 45 min after washout. 4. In conclusion, the natural coumarin DeltaF508-CFTR activators may represent a new class of natural lead compounds for the development of pharmacological therapies for CF caused by the DeltaF508 mutation.
Subject(s)
Coumarins/pharmacology , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Ion Channel Gating/drug effects , Animals , Bacterial Proteins , Biological Products/chemistry , Cell Line , Coumarins/chemistry , Dose-Response Relationship, Drug , Humans , Kinetics , Luminescent Proteins , Molecular Structure , Rats , Rats, Inbred F344 , Thyroid Gland/cytologyABSTRACT
AIM: To develop a method for assessing sperm function by measuring released acrosin activity during the acrosome reaction (AR). METHODS: Human semen samples were obtained from 24 healthy donors with proven fertility after 3-7 days of sexual abstinence. After collection, samples were liquefied for 30 min at room temperature. Standard semen parameters were evaluated according to World Health Organization (WHO) criteria. Calcium ionophore A23187 and progesterone (P4) were used to stimulate the sperm to undergo AR. After treatment, sperm were incubated with the supravital dye Hoechst33258, fixed in a glutaraldehyde-phosphate-buffered saline solution, and the acrosomal status was determined by fluorescence microscopy with fluorescein isothiocyanate-labeled Pisum sativum agglutinin (FITC-PSA). The percentage of sperm undergoing AR (AR%) was compared to sperm acrosin activities as assessed by spectrocolorimetry. The correlation between AR% and acrosin activity was determined by statistical analysis. RESULTS: The AR% and released acrosin activity were both markedly increased with A23187 and P4 stimulation. Sperm motility and viability were significantly higher after stimulation with P4 versus stimulation with A23187 (P < 0.001). There was a significant positive correlation between released acrosin activity and AR% determined by FITC-PSA staining (r=0.916, P < 0.001). CONCLUSION: Spectrocolorimetric measurement of released acrosin activity might serve as a reasonable alternative method to evaluate AR.
