Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Ten-point guide on the management of healthy women carrying BRCA1/2 mutations.

Healthy women carrying pathogenic germline mutations in BRCA1 or BRCA2 genes have an increased risk of breast and ovarian cancer. Prophylactic gynecological surgery includes risk-reducing bilateral salpingo-oophorectomy, which, in selected cases, can be combined with hysterectomy. Prophylactic gynecological surgery is recommended after completion of childbearing and can be performed for women aged 35 or more for BRCA1 or 40 or more for BRCA2 mutation carriers. Risk-reducing bilateral salpingo-oophorectomy has several adverse effects related to estrogen deprivation, and so hormonal therapy could be the main strategy for healthy women. However, health professionals have many doubts about whether they are able to offer clear counseling on the management of early menopausal symptoms (i.e. vasomotor and genitourinary symptoms) in healthy women with a hereditary predisposition to female cancer. This 'Ten-Point Guide' summarizes the evidence regarding prophylactic gynecological surgery and supports healthcare providers in the management of healthy women carrying germline BRCA1 and BRCA2 mutations.

Osmotic behaviour of human mesenchymal stem cells: Implications for cryopreservation.

Aimed at providing a contribution to the optimization of cryopreservation processes, the present work focuses on the osmotic behavior of human mesenchymal stem cells (hMSCs). Once isolated from the umbilical cord blood (UCB) of three different donors, hMSCs were characterized in terms of size distribution and their osmotic properties suitably evaluated through the exposure to hypertonic and isotonic aqueous solutions at three different temperatures. More specifically, inactive cell volume and cell permeability to water and di-methyl sulfoxide (DMSO) were measured, being cell size determined using impedance measurements under both equilibrium and dynamic conditions. Experimental findings indicate that positive cell volume excursions are limited by the apparent increase of inactive volume, which occurs during both the shrink-swell process following DMSO addition and the subsequent restoration of isotonic conditions in the presence of hypertonic solutions of impermeant or permeant solutes. Based on this evidence, hMSCs must be regarded as imperfect osmometers, and their osmotic behavior described within a scenario no longer compatible with the simple two-parameter model usually utilized in the literature. In this respect, the activation of mechano-sensitive ion-channels seemingly represents a reasonable hypothesis for rationalizing the observed osmotic behavior of hMSCs from UCB.

Insights on Cryopreserved Sheep Fibroblasts by Cryomicroscopy and Gene Expression Analysis.

Cryopreservation includes a set of techniques aimed at storing biological samples and preserving their biochemical and functional features without any significant alterations. This study set out to investigate the effects induced by cryopreservation on cultured sheepskin fibroblasts (CSSF) through cryomicroscopy and gene expression analysis after subsequent in vitro culture. CSSF cells were cryopreserved in a cryomicroscope (CM) or in a straw programmable freezer (SPF) using a similar thermal profile (cooling rate -5°C/min to -120°C, then -150°C/min to -196°C). CSSF volume and intracellular ice formation (IIF) were monitored by a CM, while gene expression levels were investigated by real-time polymerase chain reaction in SPF-cryopreserved cells immediately after thawing (T0) and after 24 or 48 hours (T24, T48) of post-thaw in vitro culture. No significant difference in cell viability was observed at T0 between CM and SPF samples, while both CM and SPF groups showed lower viability (p < 0.05) compared to the untreated control group. Gene expression analysis of cryopreserved CSSF 24 and 48 hours post-thawing showed a significant upregulation of the genes involved in protein folding and antioxidant mechanisms (HPS90b and SOD1), while a transient increase (p < 0.05) in the expression levels of OCT4, BCL2, and GAPDH was detected 24 hours post-thawing. Overall, our data suggest that cryostored CSSF need at least 24 hours to activate specific networks to promote cell readaptation.