Candida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans , which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, C. albicans releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the PRA1 gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of PRA1 prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.

The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC₅₀ values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.

NIR spectroscopy is a non-destructive tool for in-situ, on-line bioprocess monitoring. One of its most frequent applications is the determination of metabolites during cultivation, especially glucose. Previous studies have usually investigated the applicability of Near Infrared (NIR) spectroscopy at one bioreactor scale but the effect of scale up was not explored. In this study, the complete scale up from shake flask (1 L) through 20 L, 100 L and 1000 L up to 5000 L bioreactor volume level was monitored with on-line NIR spectroscopy. The differences between runs and scales were examined using principal component analysis. The bioreactor runs were relatively similar regardless of scales but the shake flasks differed strongly from bioreactor runs. The glucose concentration throughout five 5000 L scale bioreactor runs were predicted by partial least squares regression models that were based on pre-processed spectra of bioreactor runs and combinations of them. The model that produced the lowest error of prediction (4.18 mM on a 29 mM concentration range) for all five runs in the prediction set was based on the combination of 20 L and 100 L data. This result demonstrated the capabilities and the limitations of an NIR system for glucose monitoring in mammalian cell cultivations.

Background and Objectives: To assess the improvement on pelvic floor distress (PFD)‐related urogenital symptoms using validated questionnaires after intravaginal CO₂ laser treatment.Study Design/Materials and Methods: Forty postmenopausal women with genitourinary symptoms of menopause (GSM) were enrolled into this prospective cohort study and underwent vaginal laser treatment using MonaLisa Touch® fractional CO ₂ laser system. Patients received three vaginal laser treatments with 360° probe 4 weeks apart. A three‐component Pelvic Floor Distress Inventory (PFDI‐20) validated questionnaire was filled out by each patient before each session and 4 weeks after the final treatment. Wilcoxon rank sum test was used to compare the before and after treatment scores.Results: Pelvic Organ Prolapse Distress Inventory (POPDI‐6) scores were not significantly different after the first treatment compared with baseline (mean ± standard deviation [SD], 21 ± 18 vs. 17 ± 15, P = 0.44). However, each subsequent treatment resulted in further, statistically significant improvement in symptom scores (14 ± 15, P = 0.03 and 13 ± 13, P = 0.01, after the second and third treatments, respectively). Similarly, Urinary Distress Inventory (UDI‐6) scores were not significantly different after the first laser treatment (mean ± SD, 36 ± 25 vs. 29 ± 23, P = 0.36). After the second and third treatments there were significant improvement in the standardized scores (24 ± 20, P = 0.03 and 22 ± 21, P = 0.01). Colorectal‐Anal Distress Inventory (CRADI‐8) scores did not change significantly after three laser treatments.Conclusions: Three sessions of microablative fractional CO₂ vaginal laser treatment significantly improves patient reported urinary and pelvic organ prolapse symptoms. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.