Ospemifene plus fractional CO2 laser: a powerful strategy to treat postmenopausal vulvar pain.

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO2 laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60 mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene + laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene + laser group compared with the laser treatment group (-87% vs - 34%, respectively), and the vestibular health score started declining faster in the ospemifene + laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.

Endometrial response of beef heifers on day 7 following insemination to supraphysiological concentrations of progesterone associated with superovulation.

Ovarian stimulation is a routine procedure in assisted reproduction to stimulate the growth of multiple follicles in naturally single-ovulating species including cattle and humans. The aim of this study was to analyze the changes induced in the endometrial transcriptome associated with superovulation in cattle and place these observations in the context of our previous data on changes in the endometrial transcriptome associated with elevated progesterone (P4) concentrations within the physiological range and those changes induced in the embryo due to superovulation. Mean serum P4 concentrations were significantly higher from day 4 to day 7 in superovulated compared with unstimulated control heifers (P < 0.05). Between-group analysis revealed a clear separation in the overall transcriptional profile of endometria from unstimulated control heifers (n = 5) compared with superovulated heifers (n = 5). This was reflected in the number of differentially expressed genes (DEGs) identified between the two groups with 795 up- and 440 downregulated in superovulated endometria. Ten times more genes were altered by superovulation (n = 1,234) compared with the number altered due to elevated P4 within physiological ranges by insertion of a P4-releasing intravaginal device (n = 124) with only 22 DEGs common to both models of P4 manipulation. Fewer genes were affected by superovulation in the embryo compared with the endometrium, (443 vs. 1,234 DEGs, respectively), and the manner in which genes were altered was different with 64.5% of genes up- and 35.5% of genes downregulated in the endometrium, compared with the 98.9% of DEGs upregulated in the embryo. In conclusion, superovulation induces significant changes in the transcriptome of the endometrium which are distinct from those in the embryo.

Influence of season on corpus luteum structure and function and AI outcome in the Italian Mediterranean buffalo (Bubalus bubalis).

The aim was to ascertain whether relationships between corpus luteum (CL) vascularization, CL function, and pregnancy outcome in AI in buffaloes were consistent across the breeding season and transition period to the nonbreeding season in a Mediterranean environment. Stage of the estrous cycle in Italian Mediterranean buffaloes was synchronized using the Ovsynch with timed AI program and buffaloes were mated by AI in both the breeding season (N = 131) and transition period (N = 125). Detailed investigation of CL structure and function was undertaken in 39 buffaloes at each of the respective times using realtime B-mode/color-Doppler ultrasonography on Days 10 and 20 after AI. Progesterone (P4) concentrations were determined by RIA in all buffaloes. Pregnancy rate on Day 45 after AI was greater (P < 0.05) during the breeding season (58.0%) than the transitional period (45.6%) and this was primarily the result of a lower (P < 0.05) late embryonic mortality during the breeding season (7.3%) compared with the transition period (23%). Circulating concentrations of P4 on Days 10 and 20 after AI were greater (P < 0.01) during the breeding season (4.6 ± 0.3 and 3.4 ± 0.2, respectively) than during the transition period (1.6 ± 0.12 and 1.8 ± 0.2, respectively), and this was independent of reproductive status as there was no interaction between pregnancy and season. Corpus luteum time average medium velocity at Day 10 after AI was greater (P < 0.01) during the breeding season (19.3 ± 1.5) than in the transitional period (8.3 ± 0.7). There were positive correlations in pregnant buffaloes between CL time average medium velocity and P4 concentrations on Day 10 (r = 0.722; P < 0.01) and Day 20 (r = 0.446; P < 0.01) after AI. The findings were interpreted to indicate that relationships between CL vascularization, CL function, and pregnancy outcome in AI in buffaloes are consistent across the breeding season and transition period to the nonbreeding season. The distinction between the breeding season and the transition period is the relatively low proportion of buffaloes that have CL function and P4 concentrations required to establish a pregnancy during the transition period, which is manifested in a greater incidence of embryonic mortality.

[Short-course treatment of vulvovaginal candidiasis: comparative study of fluconazole and intra-vaginal fenticonazole]. / Il trattamento "short course" della candidosi vulvovaginale acuta: studio comparativo tra il fluconazolo ed il fenticonazolo intravaginale.

AIM: The aim of this paper was to compare the efficacy of fluconazole 150 mg and intra-vaginal fenticonazole 600mg in short-course treatment of the acute episode of vulvovaginal candidiasis (VVC). METHODS: In a prospective study, 80 patients with clinical and mycological (SavvyCheck™ test) confirmed VVC were enrolled and divided randomly in two groups. Forty patients received oral fluconazole (150 mg), whereas 40 patients received intra-vaginal tablet fenticonazole (600 mg). Two sequential doses of azole agents were given 3 days apart (short-course treatment). Second and third visits were done for all patients seven and 30±5 days after treatment. RESULTS: At the second visit, 31 patients (77.5%) were cured clinically (Sobel score <4) in fluconazole group and 32 patients (80%) in fenticonazole group (P=0.876). The vulvovaginal pruritus was reduced in lower time in fenticonazole patients than in fluconazole group (mean 2.3 days versus 4.5 days, P=0.047). At the third visit, three patients in fluconazole group and two patients in fenticonazole group had clinical sign of VVC. CONCLUSION: Fluconazole and intravaginal fenticonazole are both effective to cure symptoms of VVC but fenticonazole appears to reduce the pruritus in less time.

The recurrent vulvovaginal candidiasis: proposal of a personalized therapeutic protocol.

Background. Recurrent vulvovaginal candidiasis (RVC) is an increasing challenge in clinical practice. Objective. The purpose of this study was to reduce the episodes of RVC through the intake of fluconazole 200 mg/dose with a personalized regimen at growing administration intervals with a probiotic. Method. 55 patients received a 200 mg fluconazole as an induction dose for 3 alternate days. Symptoms resolution after 10-14 days made the patients eligible to continue with a maintenance therapy of fluconazole weekly for one month, followed by 200 mg after 10, 15, 20 and 30 days. Patients were allowed to move on to the next level of maintenance therapy only if they were symptom free. Patients were also given a probiotic with Beta Glucan and Echinacea Purpurea. Results. Among the 55 patients enrolled, four (7%) have withdrawn after the induction phase. 51 patients completed the whole therapeutic maintenance period, and eight (15,6%) experienced a recurrence before the end of the therapy. Five women (9,8%) relapsed (two after 2 months and three after 6 months). Conclusion. The positive results of our study prove the effectiveness of an individualized protocol for a rather short period, with a slowly decreasing administration of fluconazole + probiotic.

The influence of gamete co-incubation length on the in vitro fertility and sex ratio of bovine bulls with different penetration speed.

The objectives of this work were to evaluate whether the sperm penetration speed is correlated to the in vitro fertility and whether adapting the gamete co-incubation length to the kinetics of the bull improves in vitro fertility and affects the sex ratio. In vitro matured oocytes were co-incubated with spermatozoa from four different bulls (A-D). At various post-insemination (p.i.) times (4, 8, 12, 16 and 20 h), samples of oocytes were fixed and stained with DAPI for nuclei examination, while the remaining ones were transferred into culture to evaluate embryo development. The blastocysts produced were sexed by PCR. Two bulls (A and B) had faster kinetics than the others (C and D), as shown by the higher penetration rates recorded at 4 h p.i. (43%, 30%, 11% and 6%, respectively for bulls A, B, C and D; p<0.01). The differences in the kinetics among bulls did not reflect their in vitro fertility. The incidence of polyspermy was higher for faster penetrating bulls (36%, 24%, 16% and 4%, respectively for bulls A, B, C and D; p<0.01) and at longer co-incubation times (0%, 16%, 19%, 30% and 34%, respectively at 4, 8, 12, 16 and 20 h p.i.; p<0.01). The fertilizing ability of individual bulls may be improved by adapting the co-incubation length to their penetration speed. A sperm-oocyte co-incubation length of 8 h ensured the greatest blastocyst yields for the two faster penetrating bulls. On the contrary, 16 h co-incubation was required to increase (p<0.01) cleavage rate of the two slower bulls. Bulls with a faster kinetics did not alter the embryo sex ratio towards males. The female/male (F/M) ratios recorded were 2.1, 1.4, 1.2, 1.3 and 1.6, respectively at 4, 8, 12, 16 and 20 h p.i.

The role of hypoxia in erectile dysfunction mechanisms.

Chronic hypoxia is related to many pathological conditions: aging, heart and respiratory failure, sleep apneas, smoke, chronic obstructive pulmonary disease (COPD), diabetes, hypertension and arteriosclerosis, all characterized by reductions of sleep-related erections (SREs) and by erectile dysfunction (ED). Sleep-related erections occur naturally during rapid eye movement (REM) sleep in sexually potent men. Hypoxia is also a physiological condition at altitude. The level of inspired oxygen decreases progressively with the increase of altitude; for this reason, this study was performed to evaluate the relationship of SREs with hypoxic environment. SREs have been recorded by an erectometer (RigiScan) on three mountain climbers (mean age: 32.5) during a 26-day stay at an altitude ranging from 2000 to 5600 m above sea level. Twenty-four records have been made at progressively increasing altitudes. A data analysis was carried out on a statistical mean of the three values of each variable and an analysis of variance (ANOVA) and Newman-Keuls test were carried out for multiple comparison among groups. At altitudes over 4450 m, we found lack of rigidity at 80-100% and 60-79%. Mean % of rigidity and rigidity time of 80-100% (tip and base) decreased progressively with altitude. No significant reductions were shown in rigidity time at 0-19% and at 20-39% (tip and base), of total number, of total and mean duration of SREs. Pathological rigidometric records at high altitude in sexually potent men at sea level clarify the primary role of hypoxia in physiopathological ED pathway.

PI3K/Akt and ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17beta-estradiol and growth factors.

Cell motility and invasion are crucial events for endometrial cells, not only for the establishment of pathological states but also during the physiological tissue remodelling that occurs during the menstrual cycle and embryo implantation. We have characterized these phenomena in endometrial stromal cells evaluating cell migration-specific stimuli and the biochemical pathways involved. Ability of endometrial cells to migrate on collagen type IV substrate was evaluated by means of chemotaxis experiments. Modulation of this phenomenon by different growth factors and steroid hormones and their ability to activate extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/Akt signalling in this context were examined. Platelet-derived growth factor (PDGF)-BB, epidermal growth factor and fibroblast growth factor-2 as chemoattractant agents stimulated basal migration of endometrial stromal cells through the rapid activation of both ERK1/2 and PI3K/Akt signalling pathways. Experiments using wortmannin and PD98059, specific inhibitors of the PI3K/Akt and ERK1/2 activity, respectively, showed that the activation of both pathways is required for growth-factor-induced cell motility responses. Similarly, 17beta-estradiol (10(-6)-10(-8) M) could enhance both constitutive and PDGF-induced migration of the cells and their rapid treatment with the hormone significantly increased phosphorylation of ERK1/2 and Akt. Conversely, progesterone did not interfere with the basal migration but inhibits the PDGF-induced motility of this cell type. Rapid activation of intracellular signalling cascades ERK1/2 and PI3K/Akt by growth factors and estrogens is involved in the migration of normal endometrial stromal cells.

Genetics of endometriosis.

UNLABELLED: Endometriosis is a multifactorial disease that can affect up to 10-15% of women in their reproductive age. Epidemiological studies indicate that it is a polygenic disorder with recurrence risks in first-degree relatives of about 5-7%. Thus, the present aim of different research groups is to identify genetic variations in obvious candidate gene that could be associated with an increased susceptibility to endometriosis. The great advancement in molecular biology techniques make this task certainly possible, although particular attention needs to be paid to the study design in order to achieve reliable RESULTS: The data obtained by such studies will allow to expand our knowledge on the pathogenesis of the disease and, more importantly, to develop individualized therapies and prevention strategies to apply at high-risk populations.

Effects of cue manipulation on performance by old and young rats in a test of non-matching-to-sample.

In a study of the effects of age on cue utilization, groups of young and old rats were administered three versions of a non-matching-to-sample task that could be solved only by using spatial stimuli, local stimuli, or response cues respectively. The delay between sample and test runs was varied between 0 and 60 s. The old rats were severely impaired in spatial and local stimulus versions but the performance of old and young groups was comparable in the response version of the task. In the Response-cue task, where the old rats displayed substantial learning, their performance deteriorated more than that of the young rats when the delay was increased from 0 to 60 s.