Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis.

Study Question: Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? Summary Answer: E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. What is Known Already: E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis. Study Design, Size, Duration: This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9). Participants/Materials, Setting, Methods: E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline. Main Results and the Role of Chance: A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P < 0.05). On the other hand, the expression of mesenchymal genes such as c-Myc, Vimentin, neuronal-Cadherin and sushi domain containing 2 remained unchanged. Cabergoline treatment induced a significant reduction of the E-MSC angiogenic potential (P < 0.05 versus control). Large Scale Data: Not applicable. Limitations, Reasons for Caution: Further studies are necessary to investigate the cellular and molecular mechanisms underlying the endothelial cell differentiation. Wider Implications of the Findings: E-MSCs may undergo endothelial differentiation, and be potentially involved in the development of endometriotic implants. Cell culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment. Study Funding/Competing Interest(s): This study was supported by the 'Research Fund ex-60%', University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Salpingoscopic and laparoscopic investigations in relation to fertility outcome.

STUDY OBJECTIVE: To evaluate the correlation between salpingoscopic and laparoscopic findings and their relation to reproductive outcomes. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Ninety-one infertile women. INTERVENTION: Salpingoscopy and laparoscopy. MEASUREMENTS AND MAIN RESULTS: Salpingoscopic findings were expressed according to a widely used classification. Tubal morphology at laparoscopy was defined as regular (normal morphology), convoluted (any kind of distortion or adhesion), or hydrosalpinx. Laparoscopic and salpingoscopic findings did not correlate. Seventeen pregnancies occurred within 1 year from the procedures. According to life table analysis, the cumulative pregnancy rate was significantly higher in women with endotubal morphology showing minimal or no tubal damage, than in women with higher grades of endotubal damage. Conversely, tubal morphology at laparoscopy was not able to predict pregnancy outcome. CONCLUSION: Laparoscopy alone might not be sufficient to predict tubal integrity. Performing salpingoscopy with laparoscopy could significantly increase accuracy in predicting short-term fertility outcome. Given its low complication rate and brief duration, salpingoscopy should have a primary role in management of infertility.

Asymptomatic bacteriuria in pregnancy: a diagnostic and therapeutic approach.

Pregnancy is a predisposing factor for urinary tract infection and pregnant women suffering from this pathology are exposed to dangerous risks which may condition maternal wellbeing and fetal prognosis. The apparently paradoxal finding of a higher incidence of perinatal problems in pregnant women with asymptomatic bacteriuria compared to those with manifest infections may be explained by the fact that the latter are adequately treated, whereas asymptomatic bacteriuria, which is difficult to diagnose, may continue in a subtle form for the entire duration of pregnancy. This emphasises the importance of the early diagnosis of infection using a protocol based on urine tests and urine culture and the adequate treatment of all cases of asymptomatic bacteriuria in order to reduce the incidence of maternal and fetal complications (acute pyelonephritis, increased fetal morbidity and mortality). The choice of the antibiotic to be used must be made on the basis of the urine culture test, the stage of gestation, maternal clinical data and the characteristics of the antibiotic itself (pharmacokinetics, maternal and fetal toxicity). With regard to the treatment protocol, the "single-dose" protocol is currently preferred. After negative urine culture tests, all patients must carry out a complete urine test each month with hormonal and echographic monitoring of the fetoplacental unit.

Asymptomatic bacteriuria in pregnancy: maternal and fetal complications.

From an analysis of the data reported in the literature it is clear that pregnancy is a predisposing factor for urinary tract infection and that pregnant women with this pathology are exposed to dangerous risks which may influence maternal wellbeing and fetal prognosis. Authors do not concur on the specific risks to the mother and fetus, one reason being that the statistics reported to date reveal discrepancies relating to the presence of disorders prior to pregnancy and the environmental, working and socio-hygienic conditions of the populations studied. The apparently paradoxical finding of a higher incidence of perinatal problems in pregnant women with asymptomatic bacteriuria compared to manifest forms can be attributed to the fact that the latter are treated with adequate therapies whereas asymptomatic bacteriuria, which is difficult to diagnose, may persist throughout pregnancy. This underlines the importance of early diagnosis using a protocol which entails the execution of serial urine tests and urine cultures and adequate treatment of all cases of asymptomatic bacteriuria in order to reduce the incidence of urinary tract infections and materno-fetal complications. Non-treated asymptomatic bacteriuria in fact represents a considerable risk factor since it may lead to the onset of acute pyelonephritis in approximately 5% of pregnant women and may increase the risk of fetal mortality.

[Intramuscular beta-interferon in the treatment of cervical intraepithelial neoplasia (CIN) associated with human papilloma virus (HPV) infection]. / Beta-interferone per via intramuscolare nel trattamento delle neoplasie cervicali intraepiteliali (CIN) associate ad infezione da human papilloma virus (HPV).

In an attempt to find less aggressive and more efficacious tools for the treatment of cervical neoplasia (CIN) associated with genital HPV infection, the authors have examined a therapeutic approach based on the strengthening of natural defences. For this purpose, a group of 10 patients diagnosed with CIN associated with HPV infection received beta-IFN therapy at a dose of 300,000 UI/die i.m. for 7 days, continuing the same dose on alternate days for 2 weeks. At the end of the follow-up results were satisfactory especially if compared with those from a control group of 9 patients. These results appear to indicate beta-IFN as the treatment of choice in HPV infections in young women wishing to have children in order to preserve the anatomic and functional integrity of the lower genetical tract.

[Antibiotic prophylaxis with cefotaxime in gynecological endoscopy]. / Profilassi antibiotica con cefotaxime nell'endoscopia ginecologica.

It is now well known that even short operations of limited scope lower the body's defences by influencing the immune system. As a result this leads to a change in microbial flora which encourages an increase in the number of Gram-negative, aerobic, anaerobic and enterococcal colonies. In order to prevent infective postoperative complications which might occur after endoscopic surgery, the authors suggest using a series of valuable recommendations which are reported in this paper. Among these the most important is antibiotic prophylaxis which is able to limit the episodes of infection, thus making a positive contribution to the postoperative iter. Cefotaxime was chosen by the authors since this molecule offers both reliable and efficacious prophylaxis as has also been shown by other studies in the obstetrics and gynecological field. The results obtained by this study fully concord with data reported in the literature.

Antineoblastic activity of antioxidant vitamins: the role of folic acid in the prevention of cervical dysplasia.

The authors made a study on 90 patients affected by various degrees of uterine cervix dysplasia searching for folic acid plasmatic concentrations. The team members affected by CIN have been compared with a test team consisting of women with normal pap-test and vaginoscopy. The study proved that the average levels of folic acids have significantly decreased in cases of dysplasia compared with the test team. These results allow stating that low folic acid plasmatic concentrations may be associated with cervix neoplasms development.

Danazol in the treatment of endometrial hyperplasia.

The paper reports the results of a study performed in 62 menorrhagic women with endometrial hyperplasia treated with Danazol. The efficacy and tolerability of the above drug was found to be satisfactory.

Perinatal mortality and morbidity in premature birth.

In a study carried out in 100 cases of premature birth in Section "A" of the Department of Gynecology and Obstetrics of the University of Turin, the authors report a perinatal mortality rate of 5.4%. Perinatal morbidity was found to be very high (68.2%). These findings--which are perfectly in line with those reported in the literature--explain why premature birth is one of the most important topics of research in modern obstetrics.

[Cholestasis in pregnancy]. / La colestasi gravidica.

The authors report the main morphological and functional alterations of the liver during the course of pregnancy. The size of the organ does not change and there is a slight (20%) reduction of hepatic flow. Hepatic function is partially modified in view of the following factors: reduced protein synthesis (in particular the albumin component), increased serum levels of cholesterol and triglycerides mediated by steroid hormones, inhibition of canalicular secretion and consequent diminution of the liver's excretory function, variations in serum levels of many markers of cholestasis so much so that they become unreliable due to pregnancy. The high level of sexual steroids also influences cholecystic kinetics: progesterone, in particular, negatively affects the contractile response to cholecystokinin-pancreozymin stimulus. The paper then reports some historical data including those which led to the definition of "gravidic cholestasis" as a clinical condition. The incidence of the disease varies considerably in relation to the geographical area and genetic factors. In Sweden and Finland the percentage ranges between 1 and 3%, whereas much higher values (12-22%) are reported in Chile and among the American Indians. The latest data for Italy reveal an incidence of 0.34%. The onset of disease is conditioned by familial predisposition due to an enhanced sensitivity to estrogens or excessive production of estrogenic metabolites. Among the hepatocytic changes induced by estrogens are the reduced fluidity of sinusoidal plasmatic membranes and the inhibition of vasolateral Na+K+ ATPase pump activity. The last months of gestation are characterized by a "cholestatic state" which may vary in severity from slight symptoms, to itching and idiopathic jaundice.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reconsideration and desire for tubal recanalization in women following voluntary sterilization]. / Pentimento e desiderio di ricanalizzazione tubarica dopo sterilizzazione volontaria nella donna.

PIP: More than 100 million people globally have resorted to voluntary sterilization to limit their fertility. Often negative psychological complications manifest themselves, such as depressive and remorseful feelings. The requests for tubal recanalization ranged from 1.3% to 15% according to the findings of 22 studies published between 1949 and 1969. The regret over the loss of fertility was higher among women with fewer than 4 children and among those who were sterilized after abortion. The maximum incidence of regret of 10-15% was reported in a 1959 study, and the lowest rates were reported in 1967 (1.3%) and in 1970 (2%). A review of 846 Puerto Rican women aged 15-49 years indicated a certain degree of regret in 21% and profound dissatisfaction in 11%, mainly because of young age and new partner. 25% of 497 subjects in a 1985 Montreal survey expressly requested the restoration of their fertility. Similar results were reported in a Danish study following up 547 cases of female sterilization during an observation period of 50 months. The international literature makes apparent that sterilization can be considered definitive mutilation in certain cases, which raises the question whether the woman who intends to undergo the operation possesses the intellectual, psychological, interpersonal, and social resources to make such a decision. Only absolutely freely chosen, voluntary sterilization can prevent consequences.^ieng

[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. / Efficacia del 17-beta-estradiolo per via transdermica nel trattamento della menopausa.

Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy.

[Post-menopausal osteoporosis. A true and real social disease]. / L'osteoporosi post-menopausale. Una vera e propria malattia sociale.

The use of estrogens in menopausal women leads to a marked improvement in the quality of life, with the short-term disappearance of vasomotory phenomena and changes in psychomotive equilibrium. This therapy offers two long-term advantages: the prevention of osteoporosis and the cardiovascular diseases.

[Psychosexual implications of female sterilization]. / Problemi psicosessuali connessi alla sterilizzazione femminile.

PIP: According to data of the Italian Association for Demographic Education, from 1978 to 1991 a total of 16,000 sterilizations were carried out in patients with an average age of 36 years. There was an increasing frequency of anxiety, depression, and lack of satisfaction with sexual life, and deterioration of marital life as the consequence of the operations. Psychological improvement has been reported in only a few cases. Hysterectomy, mastectomy, abortion, and sterilization produce profound psychological effects in women. The ideal candidate for such intervention should be fully aware of the choice and be well informed about the reproductive system, and aged over 30 with at least 2 children in a stable marital relationship. A 1973 review of 80 different studies carried out in 12 different countries reported that 82% of women benefited from the operation. In a study of 180 patients in Glasgow, Scotland, psychosexual disorders were found, in only 3.6%. In a 1975 report, postoperative psychiatric disturbances in sexual life were recorded in 2% of 98 women. Another study of 94 women who were sterilized did not find any medical or psychological problems but did find patients who were completely satisfied 2 years later. In a study of 50 patients who underwent surgical sterilization by the Pomeroy technique during cesarean section, sexual behavior in the women, measured as desire, frequency of intercourse, and satisfaction, was unchanged in 47, while in 3 there were only modest variations in libido and frequency of intercourse. On the basis of these reports in the majority of cases the outcome of sterilization was favorable when assessing various gynecological problems over time. On the other hand, when the candidate is a young woman the information has to be particularly detailed and scrupulous with respect to risks and the probable irreversibility of sterilization.^ieng

[The role of Papanicolaou test in gynecologic practice]. / Il ruolo del test di Papanicolaou nella practica ginecologica.

The paper analyses the importance of Papanicolaou's test in gynecological diagnostics and reports an interesting checklist drawn up by the "Istituto Superiore di Sanità" with which all women should be familiar in order to diagnose cervical cancer at an early stage.