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1.
Gynecol Oncol ; 183: 15-24, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38492474

ABSTRACT

OBJECTIVE: To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool. METHODS: Multicentric retrospective study of 48 subjects (15-45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68. RESULTS: Occult ovarian lesions were observed in 6 out of 45 cases investigated (14.6%), including one mucinous stage-I BOT (1/14), one serous stage-I BOT (1/13), 3 advanced-stage serous BOTs (3/11) and one early-stage serous EOC (1/7). Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors compared to controls (p < 0.001) and at a younger age. Significantly higher follicle atresia was encountered in the ovarian tumor group then in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. CONCLUSIONS: Personalized counseling for fertility preservation is required in the event of BOTs and early-stage EOCs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing the oncological risks according to tumor stage and histotype and fertility potential, especially at a younger age.


Subject(s)
Carcinoma, Ovarian Epithelial , Fertility Preservation , Ovarian Neoplasms , Humans , Female , Adult , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovarian Neoplasms/immunology , Retrospective Studies , Fertility Preservation/methods , Adolescent , Young Adult , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/surgery , Carcinoma, Ovarian Epithelial/immunology , Middle Aged , Neoplasm Staging , Lymphocytes, Tumor-Infiltrating/immunology , Ovary/pathology , Ovary/surgery , Ovarian Follicle/pathology
2.
Facts Views Vis Obgyn ; 15(1): 29-33, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37010332

ABSTRACT

Uterine fibroids have an impact on women's lives due to their high prevalence, physical symptoms, their consequences on patients' emotional and psychological well-being and loss of work productivity. The choice of therapeutical approaches varies depending on several factors, and therefore should be applied individually. Currently, there is an unmet need for good, reliable, uterine-sparing options. The oral GnRH antagonists (Elagolix, Relugolix, Linzagolix) represent a new alternative for the medical management of hormone-dependent gynaecological diseases such as uterine fibroids or endometriosis. They rapidly bind to the GnRH receptor, block endogenous GnRH activity and directly suppress LH and FSH production, avoiding unwanted flare-up effects. Some GnRH antagonists are marketed in combination with hormone replacement therapy add-back to counteract hypo-oestrogenic side effects. According to the registration trials, once-daily GhRH antagonist combination therapy results in a significant reduction in menstrual bleeding, as compared with placebo, and preserves bone mineral density, for up to 104 weeks. Further studies in the long term are needed to evaluate the whole impact of medical treatment of uterine fibroids on the management of this common women's disease.

3.
Eur J Obstet Gynecol Reprod Biol ; 274: 5-12, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35561567

ABSTRACT

OBJECTIVES: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. STUDY DESIGN: Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. RESULTS: Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). CONCLUSIONS: The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.


Subject(s)
Endometriosis , Endometriosis/complications , Endometriosis/epidemiology , Endometriosis/genetics , Eye Color , Female , Humans , Phenotype , Prevalence , Retrospective Studies
4.
Arch Gynecol Obstet ; 305(1): 149-157, 2022 01.
Article in English | MEDLINE | ID: mdl-34623489

ABSTRACT

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.


Subject(s)
Adenomyosis , Endometriosis , Placenta Previa , Premature Birth , Adenomyosis/complications , Endometriosis/complications , Endometriosis/epidemiology , Female , Humans , Infant, Newborn , Placenta Previa/epidemiology , Pregnancy , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Retrospective Studies
5.
BJOG ; 127(9): 1116-1121, 2020 08.
Article in English | MEDLINE | ID: mdl-32339382

ABSTRACT

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Delivery, Obstetric/adverse effects , Infectious Disease Transmission, Vertical , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious/diagnosis , Adult , COVID-19 , Female , Humans , Infant, Newborn , Italy , Male , Pandemics , Pregnancy , Pregnancy Complications, Infectious/virology , Retrospective Studies , SARS-CoV-2 , Vagina/virology
6.
Climacteric ; 22(4): 329-338, 2019 08.
Article in English | MEDLINE | ID: mdl-30628469

ABSTRACT

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.


Subject(s)
Endometriosis/therapy , Menopause , Clinical Decision-Making , Female , Humans , Hysterectomy , Ovariectomy , Salpingectomy
7.
Climacteric ; 20(5): 467-475, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28657769

ABSTRACT

OBJECTIVES: To evaluate efficacy, tolerability and safety of Monurelle Biogel® vaginal gel for treatment of vaginal dryness. METHODS: Multicenter, national, randomized, controlled vs. no-treatment, open-label study. Ninety-five postmenopausal women were randomized (48 to Monurelle Biogel® and 47 to no treatment). Primary endpoint was the change of Verbal Rating Scale (VRS) total score of vaginal atrophy (VA) symptoms after 8-week treatment. The main secondary endpoints were VRS single-item score, Vaginal Health Index (VHI) score, Maturation Index (MI), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R). RESULTS: The VRS total score was statistically significant in favor of the treatment group on day 28 (p = 0.001) but not on day 56 (p = 0.064). By excluding women who were not sexually active, the total VRS scores reached the criteria for clinical success in 27/43 subjects (62.8%) in the control arm and in 38/46 subjects (82.6%) in the treatment arm (p = 0.035) on day 56. The VHI score significantly changed in the active arm (4.71 ± 4.85 vs. 0.28 ± 1.71) (p < 0.001) on day 56. Even the MI significantly improved, with an increase in the percentage of superficial cells (p = 0.01). The improvements in both VHI and MI were still present at the follow-up visit after the discontinuation of the treatment (day 84). Sexual function and distress showed a statistical significant difference on day 56. CONCLUSIONS: Monurelle Biogel® vaginal gel applied twice daily for 8 weeks is effective in relieving vaginal dryness and other VA symptoms. Such a clinical meaningful effect persists at least 4 weeks and is supported by an improvement in the vaginal environment. Trial Registration clinicaltrials.gov Identifier: NCT02994342.


Subject(s)
Postmenopause/physiology , Vagina/pathology , Vaginal Creams, Foams, and Jellies/therapeutic use , Vaginal Diseases/drug therapy , Administration, Intravaginal , Aged , Atrophy/physiopathology , Female , Gels , Humans , Middle Aged , Quality of Life , Sexual Dysfunction, Physiological/epidemiology , Vaginal Creams, Foams, and Jellies/adverse effects
10.
Anal Chim Acta ; 701(2): 139-51, 2011 Sep 09.
Article in English | MEDLINE | ID: mdl-21801880

ABSTRACT

In the Italian oenological industry, the regular practice used to naturally increase the colour of red wines consists in blending them with a wine very rich in anthocyanins, namely Rossissimo. In the Asian market, on the other hand, anthocyanins extracted by black rice are frequently used as correctors for wine colour. This practice does not produce negative effects on health; however, in many countries, it is considered as a food adulteration. The present study is therefore aimed to discriminate wines containing anthocyanins originated from black rice and grapevine by using reliable spectroscopic techniques requiring minimum sample preparation. Two series of samples have been prepared from five original wines, that were added with different amounts of Rossissimo or of black rice anthocyanins solution, until the desired Colour Index was reached. The samples have been analysed by FT-NIR and (1)H NMR spectroscopies and the resulting spectra matrices were subjected to multivariate classification. Initially, PLS-DA was used as classification method, then also variable selection/classification methods were applied, i.e. iPLS-DA and WILMA-D. The classification with variable selection of NIR spectra permitted to classify the test set samples with an efficiency of about 70%. Probably these not excellent performances are due to the matrix effect, together with the lack of sensitivity of NIR with respect to minor compounds. On the contrary, very satisfactory results were obtained on NMR spectra in the aromatic region between 6.5 and 9.5 ppm. The classification method based on wavelet-based variables selection, permitted to reach an efficiency in validation greater than 95%. Finally, 2D correlation analysis was applied to FT-NIR and (1)H NMR matrices, in order to recognise the spectral zones bringing the same chemical information.


Subject(s)
Anthocyanins/analysis , Magnetic Resonance Spectroscopy/methods , Spectroscopy, Near-Infrared/methods , Wine/analysis , Fourier Analysis , Hydrogen/chemistry , Least-Squares Analysis , Oryza/chemistry , Principal Component Analysis , Vitis/chemistry
12.
Anal Chim Acta ; 643(1-2): 67-73, 2009 Jun 08.
Article in English | MEDLINE | ID: mdl-19446065

ABSTRACT

Nine different types of Italian red wines of four different varieties were analysed, without any sample pre-treatments, by voltammetric techniques using a poly(3,4-ethylenedioxythiophene)-modified electrode. The data matrices consisting of the currents measured at different potentials, by repeated Cyclic Voltammetry or Differential Pulse Voltammetry, are submitted to chemometric analysis. After explorative tests based on Principal Component Analysis, Partial Least Squares-Discriminant Analysis classification models are built both for the training and for the test sets. To this aim, different classification strategies are adopted, considering the responses from the two techniques either separately or joined together to form a data matrix including the whole voltammetric information.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemistry , Electrochemistry/instrumentation , Electrochemistry/methods , Polymers/chemistry , Wine/analysis , Wine/classification , Discriminant Analysis , Electrodes , Least-Squares Analysis , Reproducibility of Results
13.
Glia ; 57(7): 791-806, 2009 May.
Article in English | MEDLINE | ID: mdl-19031444

ABSTRACT

Endocannabinoids are a family of endogenous signaling molecules that modulate neuronal excitability in the central nervous system (CNS) by interacting with cannabinoid (CB) receptors. In spite of the evidence that astroglial cells also possess CB receptors, there is no information on the role of endocannabinoids in regulating CNS function through the modulation of ion channel-mediated homeostatic mechanisms in astroglial cells. We provide electrophysiological evidence that the two brain endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) markedly depress outward conductance mediated by delayed outward rectifier potassium current (IK(DR)) in primary cultured rat cortical astrocytes. Pharmacological experiments suggest that the effect of AEA does not result from the activation of known CB receptors. Moreover, neither the production of AEA metabolites nor variations in free cytosolic calcium are involved in the negative modulation of IK(DR). We show that the action of AEA is mediated by its interaction with the extracellular leaflet of the plasma membrane. Similar experiments performed in situ in cortical slices indicate that AEA downregulates IK(DR) in complex and passive astroglial cells. Moreover, IK(DR) is also inhibited by AEA in NG2 glia. Collectively, these results support the notion that endocannabinoids may exert their modulation of CNS function via the regulation of homeostatic function of the astroglial syncytium mediated by ion channel activity.


Subject(s)
Arachidonic Acids/metabolism , Astrocytes/physiology , Cerebral Cortex/physiology , Delayed Rectifier Potassium Channels/metabolism , Polyunsaturated Alkamides/metabolism , Potassium/metabolism , Animals , Antigens/metabolism , Calcium/metabolism , Cannabinoid Receptor Modulators/metabolism , Cell Membrane/physiology , Cells, Cultured , Cerebral Cortex/cytology , Cytosol/metabolism , Endocannabinoids , Glycerides/metabolism , Membrane Potentials , Microglia/metabolism , Neurons/metabolism , Proteoglycans/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Cannabinoid/metabolism
14.
Anal Chim Acta ; 614(2): 213-22, 2008 May 05.
Article in English | MEDLINE | ID: mdl-18420054

ABSTRACT

The voltammetric responses on selected white wines of different vintages and origins have been systematically collected by three different modified electrodes, in order to check their effectiveness in performing blind analysis of similar matrices. The electrode modifiers consist of a conducting polymer, namely poly(3,4-ethylenedioxythiophene) (PEDOT) and of composite materials of Au and Pt nanoparticles embedded in a PEDOT layer. Wine samples have been tested, without any prior treatments, with differential pulse voltammetry technique. The subsequent chemometric analysis has been carried out both separately on the signals of each sensor, and on the signals of two or even three sensors as a unique set of data, in order to check the possible complementarity of the information brought by the different electrodes. After a preliminary inspection by principal component analysis, classification models have been built and validated by partial least squares-discriminant analysis. The discriminant capability has been evaluated in terms of sensitivity and specificity of classification; in all cases quite good results have been obtained.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemistry , Polymers/chemistry , Wine/analysis , Electrochemistry , Electrodes , Gold/chemistry , Membranes, Artificial , Nanoparticles/chemistry , Platinum/chemistry , Reproducibility of Results , Sensitivity and Specificity , Surface Properties
15.
Infez Med ; 16(4): 209-13, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19155686

ABSTRACT

We report our experience concerning bronchoalveolar lavage (BAL) in adult patients affected by haematological malignancies. BAL was performed in patients with documented pulmonary diseases not responding to empirical antibiotic and antifungal therapies. Overall, 25 bronchoscopies were performed in 24 patients. This technique led to pathogen identification in 11 out of 24 patients (45 percent). In particular, we identified four cases of tuberculosis, four of aspergillosis, two of pneumocystosis, two bacterial pneumonia and one pneumonia sustained by CMV (in two cases, pneumonia was polymicrobial). In three cases, where microbiological diagnosis had been obtained by means of other exams (blood culture, urinary antigens), BAL negativity allowed us to exclude alternative diagnoses. Pulmonary location of haematological disease was diagnosed in seven patients. BAL drove a switch therapy in 54 percent of patients. When performed by expert operators, BAL is useful and safe also in frail patients, such as those affected by onco-haematological malignancies.


Subject(s)
Bronchoalveolar Lavage , Bronchoscopy , Hematologic Neoplasms/complications , Hematologic Neoplasms/diagnosis , Immunocompromised Host , Pneumonia/diagnosis , Pneumonia/microbiology , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage/methods , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , Bronchoscopy/methods , Cytomegalovirus Infections/diagnosis , Female , Humans , Male , Middle Aged , Pneumonia/virology , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/microbiology , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/microbiology , Pulmonary Aspergillosis/diagnosis , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Tuberculosis, Pulmonary/diagnosis
16.
Mol Hum Reprod ; 13(5): 317-22, 2007 May.
Article in English | MEDLINE | ID: mdl-17350964

ABSTRACT

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.


Subject(s)
Cell Movement/physiology , Endometrium/physiology , Estradiol/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Intercellular Signaling Peptides and Proteins/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Androstadienes/pharmacology , Cell Movement/drug effects , Cells, Cultured , Chemotaxis , Endometrium/cytology , Epidermal Growth Factor/pharmacology , Estrogen Antagonists/pharmacology , Female , Fibroblast Growth Factor 2/pharmacology , Flavonoids/pharmacology , Humans , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Phosphorylation , Platelet-Derived Growth Factor/pharmacology , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Stromal Cells/physiology , Wortmannin
17.
J Mol Endocrinol ; 36(3): 415-24, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16720713

ABSTRACT

In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent anti-proliferative/immunomodulatory effects on various tissues. Consistently, the enzyme that catalyzes the synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (1alpha-OHase) and the vitamin D receptor have a widespread tissue distribution. Among site-specific functions, the hormone has been suggested to be involved in uterine physiology. However, molecular analysis of the vitamin D system in normal endometrium throughout the menstrual cycle as well as its regulation in the context of endometrial physiological and pathological events have received very limited attention. Thus, we have studied expression, localization and regulation of 1alpha-OHase in human cycling and early pregnant endometrium. The capacity for 1alpha-hydroxylation and the presence of vitamin D receptor in endometrial cells have also been evaluated. The functional significance of these findings has been tested by evaluating gene expression of the catabolic enzyme, vitamin D 24-hydroxylase, and of the adhesion protein, osteopontin. Finally, to verify any potential dysfunction of the vitamin D system in endometriosis, a reproductive disease characterized by immune-mediated anomalies, we have analyzed expression of 1alpha-OHase in both eutopic and ectopic endometrium of affected patients. Results obtained showed that the active form of the 1alpha-OHase gene was expressed in human endometrial stromal cells independent of the cycle phase but with a significant increase in early pregnant decidua. A similar profile was observed for the protein, which was abundantly expressed in the cytoplasm of both endometrial stroma and epithelial glands. Both cycling and early pregnant endometrial cells also expressed the vitamin D receptor. In the same cells, 1alpha-OHase mRNA levels were significantly stimulated by the pro-inflammatory cytokine interleukin (IL)-1beta (50 and 500 pg/ml) while addition of the active form of the hormone could modulate both CYP24 and osteopontin gene expression. The 1alpha-OHase gene was also expressed in ectopic endometrium and its levels were increased in proliferative phase cultures derived from patients with endometriosis. Human cycling endometrium may be included among the extrarenal sites able to synthesize vitamin D. The IL-1beta-mediated induction of 1alpha-OHase gene and the hormonal modulation of osteopontin support a role for the hormone in the immunological mechanisms underlying uterine function. Abnormalities of this system are present in endometriosis.


Subject(s)
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Endometrium/physiology , Gene Expression Regulation, Enzymologic , Menstrual Cycle/physiology , Vitamin D/metabolism , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , Decidua/cytology , Decidua/physiology , Endometriosis/enzymology , Endometrium/cytology , Female , Humans , Pregnancy , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Stromal Cells/cytology , Stromal Cells/physiology
18.
Hum Reprod ; 19(8): 1871-6, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15218003

ABSTRACT

BACKGROUND: Recent studies have proposed the measurement of CA 19-9 and IL-6 as an alternative to CA 125 as markers for endometriosis. This study was performed in order to verify the clinical value of serum CA 125, CA 19-9 and IL-6 levels, either by themselves or combined, in the detection of the disease. METHODS: In a prospective cohort study, serum concentrations of CA 125, CA 19-9 and IL-6 were measured in a consecutive series of 80 women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. RESULTS: Endometriosis was documented in 45 women (stage I-II in 14 cases and stage III-IV in 31 cases). Patients with endometriosis had significantly higher levels of CA 125 than controls [23.4 IU/ml (13.3-37.6) versus 11.4 IU/ml (9.1-18.5), P < 0.001)]. Conversely, women with and without the disease were shown to have similar levels of both IL-6 pg/ml [0.6 (undetectable-1.4) versus 1.0 pg/ml (0.4-1.9), P = 0.09] and CA 19-9 [9.8 IU/ml (4.5-20.8) versus 7.4 IU/ml (2.8-11.5), P = 0.11]. The area under the receiver operating characteristics curve resulted in a statistically significant difference from the null hypothesis only for CA 125 (P < 0.001). Sensitivity and specificity of CA 125 were 27 and 97% respectively and were higher than those related to CA 19-9 and IL-6. Concomitant use of the three dosages led to a sensitivity and a specificity of 42 and 71% respectively. CONCLUSIONS: The concomitant dosage of CA 125, CA 19-9 and IL-6 does not add significant information in respect to the CA 125 test alone in diagnosing either early or advanced stages of endometriosis.


Subject(s)
CA-125 Antigen/blood , CA-19-9 Antigen/blood , Endometriosis/blood , Endometriosis/diagnosis , Interleukin-6/blood , Adult , Biomarkers , Endometriosis/surgery , Female , Genital Diseases, Female/surgery , Humans , Laparoscopy
19.
Am J Obstet Gynecol ; 189(2): 545-51, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14520232

ABSTRACT

OBJECTIVE: Options for human immunodeficiency virus-1-infected women who are already receiving antiretroviral medications when they become pregnant include the continuation or discontinuation of the therapy during the first trimester. These two strategies are compared in terms of plasma human immunodeficiency virus viral load and CD4 cell count. STUDY DESIGN: Seventy women who attended the II Department of Obstetrics and Gynecology were identified. Four different periods for laboratory evaluations were decided: presuspension, suspension, second trimester, and third trimester. RESULTS: Thirty-two women (46%) discontinued antiretroviral therapy; 38 women (54%) did not. Whereas plasma HIV virus viral load and CD4 cell count did not significantly vary during pregnancy in patients who did not interrupt the therapy, these two variables were influenced significantly by the discontinuation of treatment (P<.001 for both). Human immunodeficiency virus viral load increased during the suspension period and regressed promptly to basal levels as soon as the therapy was reintroduced. A transitory decrease in CD4 cell count was also documented, but the recovery tended to be slower. CONCLUSION: The suspension of combination antiretroviral therapy during the first trimester of pregnancy transiently corresponds to an increase in human immunodeficiency virus viral load and a decline of CD4 cell count.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/administration & dosage , Pregnancy Complications, Infectious/drug therapy , RNA, Viral/blood , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/virology , Adult , CD4 Lymphocyte Count , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV-1/genetics , Humans , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , Pregnancy Trimester, First , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Viral Load
20.
J Clin Endocrinol Metab ; 88(6): 2853-9, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12788899

ABSTRACT

In all species studied, the basic fibroblast growth factor (bFGF) gene is transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS) probably involved in regulating the stability of the sense transcript. In this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women with endometriosis. bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 29 women without endometriosis and 24 patients affected by the disease. When the data were analyzed according to the phase of the menstrual cycle, endometrial stromal cells derived from patients in the late proliferative phase showed significantly higher bFGF mRNA values and significantly lower 1B FGF-AS mRNA levels compared with control samples. Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in endometrial stromal cells derived from patients compared with that in controls (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009). Moreover, for bFGF expression the differences existing at the mRNA level were maintained at the protein level. These findings support the hypothesis that 1B FGF-AS mRNA could regulate the expression of the sense transcript and suggest that in endometrial cells derived from patients, the presence of higher bFGF levels could improve their ability to proliferate at the ectopic site.


Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Oligonucleotides, Antisense/metabolism , Base Sequence/genetics , Cells, Cultured , Endometriosis/pathology , Endometrium/pathology , Female , Follicular Phase , Humans , Luteal Phase , Menstrual Cycle , Oligonucleotides, Antisense/genetics , Promoter Regions, Genetic/genetics , RNA, Messenger/metabolism
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