Collagen Vitrigel Membrane-Coated Nylon Line Prevents Stenosis After Conization of the Cervix Uteri.

Cervical stenosis is a postoperative complication of conization for uterine cervical malignancy, but a standard method of preventing this complication has yet to be established. Collagen vitrigel is a collagen-based biomaterial that has antifibrotic and epithelization promoting actions. We evaluated the antistenotic effect of an indwelling collagen vitrigel membrane-coated nylon line (CVNL) after cervical conization in rabbits. In one group of rabbits, a CVNL was placed in the cervical canal after conization. In another group, a nylon line without a collagen coating was placed in the cervical canal after conization. The control group underwent cervical conization without placement of a device. The control (conization alone) and nylon (conization plus indwelling nylon line) groups exhibited cervical swelling. Rabbits in the CVNL group (cervical conization plus indwelling CVNL in the xerogel state) had a normal cervical surface. The cervical canal in the control group was enlarged and showed cystic changes attributed to cervical stenosis. The nylon group exhibited a trend toward cervical canal dilatation. In the CVNL group, the cervical canal was normal and did not show cystic dilatation. Fibrosis occurred to a lesser degree in the nylon group than in the control group, and the CVNL group exhibited minimal interstitial fibrosis. The control and nylon groups showed increased numbers of myofibroblasts in the regenerated cervix, but few myofibroblasts were observed in the CVNL group. Abundant collagen type III was observed in regenerated cervical tissue in the control and nylon groups but not in the CVNL group. The number of proliferative mesenchymal cells in the regenerated cervix was lowest in the CVNL group. The expressions of connective tissue growth factor (CTGF, a regulator of fibroblast growth and extracellular matrix secretion), extracellular signal-regulated protein kinases 1 and 2, and c-Jun N-terminal kinase (which are involved in the induction of CTGF by transforming growth factor-ß) were lower in the CVNL group than in the control or nylon groups. This study describes an indwelling CVNL that prevents cervical stenosis and cystic changes after conization. These effects were likely mediated by inhibition of fibrosis, myofibroblast emergence, CTGF expression, and collagen type III deposition in regenerating cervix. Impact statement Collagen vitrigel is a high-density collagen material that promotes epithelization, inhibits fibrosis, and suppresses inflammation in regenerating tissue. We evaluated whether a collagen vitrigel membrane-coated nylon line would prevent cervical stenosis after conization in the rabbit. We found that an indwelling collagen vitrigel membrane-coated nylon line prevented cervical canal stenosis and cystic changes after cervical conization by inhibiting fibrosis, myofibroblast emergence, connective tissue growth factor expression, and collagen type III deposition in the regenerating cervix. Our device has potential as a new method of preventing cervical canal fibrosis and stenosis after conization for cervical cancer.

Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic Tolerance Reduction.

Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized P. aeruginosa quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against P. aeruginosa PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic P. aeruginosa biofilm infections.

Inhibitory Effects of Phenylpropanoid Derivatives from Oenanthe javanica on Antigen-Stimulated Degranulation in RBL-2H3 Cells.

Two diacyldaucic acids (1 and 2), an α,ß-unsaturated γ-lactone-type lignan (3) and its derivatives (4-6), and 12 known compounds were isolated from a traditional East Asian vegetable, Oenanthe javanica. The absolute configuration of 1 was validated by obtaining (+)-osbeckic acid through acid hydrolysis. The absolute configurations of 3-5 were determined by comparing their experimental and computed ECD data. The conclusion was supported by applying the phenylglycine methyl ester method to 3. Compound 6 was obtained as an interconverting mixture of isomers in a 3:1 trans- cis ratio. Several water-soluble components (1, 3, and 6) showed concentration-dependent inhibitory effects on antigen-stimulated degranulation in RBL-2H3 cells without producing any direct cytotoxicity against RBL-2H3 or HeLa cells.