Marina Pontillo

Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women

Circulating levels of the neuro-hypophysial nonapeptide oxytocin increase during sexual arousal and orgasm in both men and women. A few studies have evaluated the effect of the menstrual cycle on plasma oxytocin in normally cycling, sexually active, healthy fertile women using or not using contraceptive pills. In 20 ovulating women and 10 women taking an oral contraceptive (group 1 and group 2, respectively), sexual function, hormonal profile, and plasma oxytocin (OT) were evaluated throughout the menstrual cycle. In group 1, plasma OT was significantly lower during the luteal phase in comparison with both the follicular and ovulatory phases. Plasma oxytocin was significantly correlated with the lubrication domain of the Female Sexual Function Index (FSFI) during the luteal phase and showed a trend towards statistical significance during the follicular phase. In group 2, plasma OT did not show any significant fluctuation throughout the menstrual cycle, even though a significant correlation was evident with both the arousal and the lubrication domain of the FSFI during the assumption of the contraceptive pill. These findings suggest that plasma OT fluctuates throughout the menstrual cycle in normally cycling healthy fertile women with adequate sexual activity but not taking any oral contraceptive pill. Moreover, plasma OT levels significantly relates to the genital lubrication in both women taking and not taking oral contraceptive pill apparently confirming its role in peripheral activation of sexual function.

Prostate-Specific Antigen (PSA) Isoform p2PSA Significantly Improves the Prediction of Prostate Cancer at Initial Extended Prostate Biopsies in Patients with Total PSA Between 2.0 and 10 ng/ml: Results of a Prospective Study in a Clinical Setting

BACKGROUND Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers. OBJECTIVE To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center. INTERVENTION Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores). MEASUREMENTS We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA)×100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA×√tPSA]). RESULTS AND LIMITATIONS Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values<0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p<0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05). CONCLUSIONS In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.

Tumor-Derived MUC1 Mucins Interact with Differentiating Monocytes and Induce IL-10highIL-12low Regulatory Dendritic Cell

Dendritic cells (DC) initiate immunity by the activation of naive T cells and control immunity through their ability to induce unresponsiveness of lymphocytes by mechanisms that include deletion and induction of regulatory cells. An inadequate presentation to T cells by tumor-induced “regulatory” DC, among several mechanisms, can explain tolerance to tumor-associated Ags. In this study, we show that tumor-derived mucin profoundly affects the cytokine repertoire of monocyte-derived DC and switch them into IL-10highIL-12low regulatory APCs with a limited capacity to trigger protective Th1 responses. In fact, DC cocultured with pancreatic tumor cell lines in a Transwell system did not reach full maturation, had low immunostimulatory functions, did not produce IL-12, and released high levels of IL-10. The involvement of known tumor-derived immune-suppressive factors (e.g., vascular endothelial growth factor, TGF-β, IL-6, and IL-10) was considered and excluded. We provide evidence that tumor-derived MUC1 mucins are responsible for the impaired DC maturation and function. DC obtained in the presence of tumor microenvironment preferentially polarized IL-4+ response. Moreover, T cells primed by these regulatory DC became anergic and behaved as suppressor/regulatory cells. These findings identify mucin secretion as a novel mechanism of tumor escape from immune surveillance and provide the basis for the generation of potentially tolerogenic DC.

Menstrual Cycle-Related Changes in Circulating Androgens in Healthy Women With Self-Reported Normal Sexual Function

INTRODUCTION There is currently neither a clinically useful, reliable and inexpensive assay to measure circulating levels of free testosterone (T) in the range observed in women, nor is there agreement on the serum free T threshold defining hypoandrogenism that is associated with female-impaired sexual function. AIM Following the Clinical and Laboratory Standards Institute guidelines, we generated clinically applicable ranges for circulating androgens during specific phases of the menstrual cycle in a convenience sample of 120 reproductive-aged, regularly cycling healthy European Caucasian women with self-reported normal sexual function. METHODS All participants were asked to complete a semistructured interview and fill out a set of validated questionnaires, including the Female Sexual Function Index, the Female Sexual Distress Scale, and the 21-item Becks Inventory for Depression. Between 8 am and 10 am, a venous blood sample was drawn from each participant during the midfollicular (day 5 to 8), the ovulatory (day 13 to 15), and the midluteal phase (day 19 to 22) of the same menstrual cycle. MAIN OUTCOME MEASURES Serum levels of total and free testosterone, Delta(4)-androstenedione, dehydroepiandrosterone sulphate and sex hormone-binding globulin during the midfollicular, ovulatory and midluteal phase of the same menstrual cycle. RESULTS Total and free T levels showed significant fluctuations, peaking during the ovulatory phase. No significant variation during the menstrual cycle were observed for Delta(4)-androstenedione and dehydroepiandrosterone sulphate. Despite the careful selection of participants that yielded an homogeneous group of women without sexual disorders, we observed a wide range of distribution for each of the circulating androgens measured in this study. CONCLUSIONS This report provides clinically applicable ranges for androgens throughout the menstrual cycle in reproductive-aged, regularly cycling, young healthy Caucasian European women with self-reported normal sexual function.

Evaluation of the Coulter Counter S-Plus VI

This article reports an evaluation of the Coulter Counter model S-Plus VI automatic analyser for haematology, and data are presented on linearity, carry-over, precision, accuracy and stability of the instrument, when compared with a model S-Plus IV/D. The three-part differential count provided by Coulter S-Plus VI has been compared with manual eye counting. The results show a good agreement with only 2.5% of discrepancies in 2271 routine samples. Advantages of the new instrument include: reduction of running costs, largely due to manpower saving; simple and easy use, and improved operator safety, there being no need for human contact with blood.

Anti-Mullerian Hormone-to-Testosterone Ratio is Predictive of Positive Sperm Retrieval in Men with Idiopathic Non-Obstructive Azoospermia

The lack of clinically-reliable biomarkers makes impossible to predict sperm retrieval outcomes at testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA), resulting in up to 50% of unnecessary surgical interventions. Clinical data, hormonal profile and histological classification of testis parenchyma from 47 white-Caucasian idiopathic NOA (iNOA) men submitted to microdissection TESE (microTESE) were analyzed. Logistic regression analyses tested potential clinical predictors of positive sperm retrieval. The predictive accuracy of all variables was evaluated using the receiver operating characteristic-derived area under the curve, and the clinical net benefit estimated by a decision-curve analysis (DCA). Overall, 23 (49%) and 24 (51%) patients were classified as positive and negative sperm retrievals at microTESE. While circulating hormones associated to a condition of primary hypogonadism did not predict sperm retrieval, levels of anti-Mullerian hormone (AMH) and the ratio AMH-to-total Testosterone (AMH/tT) achieved independent predictor status for sperm retrieval at microTESE, with a predictive accuracy of 93% and 95%. Using cutoff values of <4.62 ng/ml for AMH and <1.02 for AMH/tT, positive sperm retrieval was predicted in all individuals, with 19 men out of 47 potentially spared from surgery. DCA findings demonstrated clinical net benefit using AMH and AMH/tT for patient selection at microTESE.

Undiagnosed prediabetes is highly prevalent in primary infertile men - results from a cross-sectional study

To study the prevalence and the risk associated with prediabetes (PreDM) in primary infertile men.

MP28-04 SENSITIVITY OF [-2]PROPSA (P2PSA) MEASUREMENTS FOR PREDICTION OF BIOCHEMICAL RECURRENCE (BCR) IN MEN AFTER RADICAL PROSTATECTOMY: A 3-YEARS PROSPECTIVE COHORT STUDY

INTRODUCTION AND OBJECTIVES: Although radical prostatectomy (RP) offers a high overall cancer control rate, even in appropriately selected men, up to a third will experience failure (biochemical recurrence: BCR). PSA has been particularly considered valuable for the detection of BCR defined as a PSA concentration of at least 0.2 ng/ml. Recently, the will to detect the earliest sign of recurrence have led to the development of ultrasensitive PSAs (uPSA), but the usefulness of ultrasensitive assays has not been established. As [-2]proPSA (p2PSA), introduced in clinical practice with its derivate PHI (prostate health index), is normally expressed in pg/mL, it could be more sensible than PSA and uPSA for detecting early BCR after RP. In this study we test the hypothesis that p2PSA (index test) may detect BCR earlier than reference standard test (tPSA) in patients who underwent RP for localised prostate cancer (PCa). METHODS: The current study is an observational, prospective, cohort study in a contemporary series of consecutive patients subjected to RP for clinically localized PCa from January 2013 to June 2013. Biochemical follow-up consisted of a blood sample for reference standard test (PSA) and index test (p2PSA), after 3-6-12-18-24-30-36 months. The blood samples were processed with the UniCel DxI800 Immunoassay System analyzer (Beckman Coulter Inc., Brea, CA, USA) and managed according to the criteria described by Semjonow et al using the Hybritech calibration. BCR was defined as a confirmatory PSA concentration of 0.2 ng/ml or greater. A value of 0.8 pg/ml was considered the Limit of Detection (LoD) for p2PSA after RP as previously described. The primary outcome was to investigate the sensitivity of both tests for BCR, while the secondary end point was to determine whether or not results are consisting with different pathological outcome. Descriptive statistical analysis were complemented by Cox proportional hazards models, McNemar test and Kaplan-Meier curves for BCR-free survival by PSA and p2PSA cut-offs RESULTS: Over 145 eligible patients, 134 men were enrolled and were followed-up for 3 years. The frequencies of positive subjects, identified with p2PSA cut-off, were significantly higher in all the followups than frequencies of positive subjects identified with PSA cut-off (p<0.0001). Overall we observed 18 BCR according to PSA. Five patients showed a contemporary increase of PSA and p2PSA, while 9 men presented a p2PSA increase earlier than PSA (mean time 4.9 3.1 months vs. 18.8 7.3 respectively). In 4 patients the increase of PSA was not associated with a p2PSA > 0.8 pg/ml. The analysis of KaplanMeier curves for BCR-free survival showed a significant lower time for p2PSA (16.7 mo; 95%CI: 14.1-19.2) respect to PSA (35.6 mo; 95%CI: 34.0-33.2). When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with pT2c-GS3+4/4+3-R1 and pT3a-R0/1 could be considered the target categories, which would benefit more from the p2PSA LoD. CONCLUSIONS: The current findings confirm that p2PSA could be more sensitive than tPSA in detecting early BCR at a mid termfollow-up (3 years). This is a confirmation of a previous paper of ours with a shorter follow-up (18 months). Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical practice purposes

Optimization of the Urinary Acid α-Glucosidase Determination

Summary: The optimization of the method for acid -glucosidase determination (EC 3.2.1.3) in human urines, employing the synthetic Substrate 4-nitrophenyl-a-/)-glucopyranoside, is reported. Storage conditions of the specimens and their pretreatment were particularly investigated. The precision of the whole analytical procedure (including gel filtration) is good (within-run CV = 7.4% for normal samples and 3.7% for elevated ones). The correlation with the method using maitose as Substrate is excellent (y = —0.01 + 0.13 x; r = 0.9893).