Genistein reduces angiogenesis and apoptosis in women with endometrial hyperplasia

Roberta Granese,1,* Alessandra Bitto,2,* Francesca Polito,2 Onofrio Triolo,1 Domenico Giordano,1 Angelo Santamaria,1 Francesco Squadrito,2 Rosario D'Anna1 1Department of Paediatric, Gynaecological, Microbiological, and Biomedical Sciences, 2Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Messina, Italy*These authors contributed equally to this workAbstract: Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatments may be available with equivalent efficacy and reduced side effects. Here, we evaluate the effect of genistein aglycone on angiogenesis and apoptosis-related markers women with endometrial hyperplasia. Premenopausals (n=38) with nonatypical endometrial hyperplasia were administered either genistein aglycone (54 mg/day, n=19) or norethisterone acetate (10 mg/day, n=19) on days 16–25 of the menstrual cycle and evaluated for 6 months. Biopsies were taken during hysteroscopy at baseline and 6 months, and symptoms including excessive uterine bleeding were assessed at baseline and 3 and 6 months following recruitment. The expression of angiogenesis (Vegf), epithelial (Egf and Tgfb), and apoptosis-related (Bax, Bcl-2, and Casp-9) molecules, were assessed in uterine biopsies at baseline and after 6 months of therapy. Follicle-stimulating hormone, luteinizing hormone, estradiol, SHBG, and progesterone levels were also measured. After 6 months, 42% of genistein aglycone-administered patients had a significant improvement of symptoms compared to 47% of norethisterone acetate subjects. No significant differences were noted in hormone levels for any treatment. Gene expression revealed a significant reduction in Vegf, Egf, and Tgfb (P<0.05 versus baseline), and an increase in proapoptotic molecules (Bax and Casp-9), with a concomitant decrease in Bcl-2 values (P<0.05) in both groups. These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women who cannot or do not wish to be treated with progestin.Keywords: genistein, endometrial hyperplasia, Vegf, Bcl-2, Bax, Casp-

The use of 3-axial accelerometers to evaluate sound production in European spiny lobster, Palinurus elephas

The European spiny lobster Palinurus elephas emits sound (“rasp”), moving the base of their antennas, as response to the presence of predator and for interspecific communication. During the last decade, three-axial accelerometers have been used to mainly describe diel activity patterns, circadian rhythms and rate of energy consumption of different lobster species, but these devices can also record sound emission in terms of mechanical vibration of carapace. In order to evaluate the efficiency of accelerometers in recording sound production (rasp events and number of pulses inside each rasp) and in discriminating of that from other behavioural events, accelerometers were used in combination with hydrophone and during mesocosm free ranging conditions. Three-axial accelerometers were able to detect sound production events in P. elephas. All the rasp events (n = 405) recorded with hydrophones were also detected by the accelerometers considering its data sampled at different frequency (from 800 Hz to 12 Hz). However, the detection of the number of pulses within each rasp sound decreased with sampling frequency of accelerometer data (median of predictive error for 800 Hz = 0.33; median of predictive error for 12 Hz = 0.65). During mesocosm free condition, three behavioural categories were identified: walk, tail flip, and rasp, the last with averaged (15.16 ± 3.52 m/s2 ) and maximum (29.49 ± 9.37 m/s2 ) values of acceleration significantly higher than the other two. Findings from this study prove that accelerometers register only lobster body vibrations providing a clear signal that is not distorted by other noises in the environment. They also allowed to identify rasps for each tagged lobster, something not possible using hydrophones in both, aquaria or natural habitat. Accelerometer resulted an useful tool to detect behaviours even with low mobility species. Moreover, the possibility to couple accelerometer and other biologging techniques would help to improve our understanding of the behaviour of a large range of free-living species.Fil: Zenone, Arturo. Istituto per l'ambiente Marino Costiero; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Ceraulo, Maria. Istituto per l'ambiente Marino Costiero; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Ciancio Blanc, Javier Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Buscaino, Giuseppa. Istituto per l'ambiente Marino Costiero; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: D'Anna, Giovanni. Consiglio Nazionale delle Ricerche; Italia. Istituto per l'ambiente Marino Costiero; ItaliaFil: Grammauta, Rosario. Consiglio Nazionale delle Ricerche; Italia. Istituto per l'ambiente Marino Costiero; ItaliaFil: Mazzola, Salvatore. Consiglio Nazionale delle Ricerche; Italia. Istituto per l'ambiente Marino Costiero; ItaliaFil: Giacalone, Vincenzo Maximiliano. Consiglio Nazionale delle Ricerche; Italia. Istituto per l'ambiente Marino Costiero; Itali

The management of vaginal agenesis: report of 104 cases

Objective: To present the results obtained in 104 cases of vaginal aplasia resolved with self-dilatation or with surgical procedures such as the McIndoe or Williams operations. Design: Retrospective study. Setting: Departments of obstetrics and gynecology of universities in Bologna, Modena, and Messina, Italy. Patient(s): One hundred four cases of vaginal aplasia. Intervention(s): Self-dilatation and surgical procedures such as the McIndoe or Williams operations. Main Outcome Measure(s): Outcome of the treatment. Result(s): From 1977 to 2002, 104 cases of vaginal agenesis were treated. The mean age of the treated patients was 16.5 years old (range, 13-18 years). After 6 months of self-dilatation, 41 subjects obtained a new cavity of about 10-12 cm in length. In 14 patients, a space ranging from 3 to 5 cm was obtained. The technique failed in 49 patients. Fourteen patients underwent the Williams surgical procedure, while the remaining 49 patients underwent to the McIndoe procedure. All patients were successfully treated, and the only complication, a rectovaginal fistula that was repaired, occurred in one case of the McIndoe operation. Conclusion(s): Self-dilatation should be the first approach because of its high success rate; the Williams surgical approach should be chosen when self-dilatation partially fails or when previous surgical attempts are unsuccessful. Finally, the McIndoe procedure and its variants should be used when self-dilatation completely fails. © 2007 American Society for Reproductive Medicine

[11-OR]: Myo-inositol in the prevention of gestational diabetes and its complications

To check the hypothesis that myo-inositol supplementation, an insulin sensitizing substance, may reduce gestational diabetes mellitus (GDM) onset and insulin resistance in obese pregnant women

Decreased endothelial progenitor cells (EPCs) and increased Natural Killer (NK) cells in peripheral blood as possible early markers of preeclampsia: a case-control analysis

PURPOSE: Endothelial Progenitor Cells (EPCs) and Natural Killer (NK) cells were recently advocates in the pathogenesis of preeclampsia (PE), since they can be mobilized into the bloodstream and may orchestrate vascular endothelium function. The aim of our study was to evaluate in early pregnancy circulating EPCs and NK cells in peripheral blood in women who later developed PE compared to uncomplicated pregnancies. METHODS: We prospectively enrolled pregnant women at 9+0-11+6 weeks of gestation at the time of first-trimester integrated screening for trisomy 21, who underwent peripheral venous blood (20 mL) sample. We included only women who later developed PE (cases) and women with uncomplicated pregnancy (controls), matched for maternal age, parity, and Body Mass Index. In these groups, we evaluated the levels of CD16+CD45+CD56+ NK cells and CD34+CD133+VEGF-R2+ EPCs in peripheral blood samples previously stored. RESULTS: EPCs were significantly lower (p &lt; 0.001), whereas NK cells were significantly higher (p &lt; 0.001) in PE group compared to uncomplicated pregnancies during the first trimester. CONCLUSION: The evaluation of EPCs and NK cells in peripheral blood during the first trimester may be considered an effective screening for the early identification of women at risk of developing PE

miRNA expression for early diagnosis of preeclampsia onset: hope or hype?

PURPOSE: Preeclampsia (PE) is a multi-systemic disease characterized by hypertension, proteinuria and other typical signs that can negatively affect the development of pregnancy. The outcome of the disease is strongly linked to the possibility of early diagnosis, in order to prevent the clinical manifestations. Pathogenesis is still unknown, although abnormalities of placenta development linked to angiogenesis alterations and abnormal trophoblastic invasion seem to be involved, corroborating the epigenetic theory. Basing on these elements, this review aims to summarize the possible role of miRNAs in PE onset, both as increased or decreased expression in placenta or as maternal serum markers. MATERIALS AND METHODS: We considered eligible all original articles (randomized, observational and retrospective studies), published between 2000 and 2016 in English language, about miRNA expression in placenta and maternal serum levels both in uncomplicated and PE pregnancies. RESULTS: Available data support a direct correlation between selective miRNAs high/low expression in placenta and maternal serum, although it is still unclear how these epigenetic changes may affect the development and outcomes of the disease. CONCLUSION: Future studies should aim to identify a robust panel of miRNA markers in order to predict the onset and development of PE

Antiosteoporotic Activity of Genistein Aglycone in Postmenopausal Women: Evidence from a Post-Hoc Analysis of a Multicenter Randomized Controlled Trial

Genistein has a preventive role against bone mass loss during menopause. However, experimental data in animal models of osteoporosis suggest an anti-osteoporotic potential for this isoflavone. We performed a post-hoc analysis of a previously published trial investigating the effects of genistein in postmenopausal women with low bone mineral density. The parent study was a randomized, double-blind, placebo-controlled trial involving postmenopausal women with a femoral neck (FN) density &lt;0.795 g/cm2. A cohort of the enrolled women was, in fact, identified at the baseline as osteoporotic (n = 121) on the basis of their T-score and analyzed thereafter for the 24 months’ treatment with either 1000 mg of calcium and 800 IU vitamin D3 (placebo; n = 59); or calcium, vitamin D3, and Genistein aglycone (54 mg/day; genistein; n = 62). According to the femoral neck T-scores, 31.3% of the genistein and 30.9% of the placebo recipients were osteoporotic at baseline. In the placebo and genistein groups, the 10-year hip fracture probability risk assessed by Fracture Risk Assessment tool (FRAX) was 4.1 ± 1.9 (SD) and 4.2 ± 2.1 (SD), respectively. Mean bone mineral density (BMD) at the femoral neck increased from 0.62 g/cm2 at baseline to 0.68 g/cm2 at 1 year and 0.70 g/cm2 at 2 years in genistein recipients, and decreased from 0.61 g/cm2 at baseline to 0.60 g/cm2 at 1 year and 0.57 g/cm2 at 2 years in placebo recipients. At the end of the study only 18 postmenopausal women had osteoporosis in the genistein group with a prevalence of 12%, whereas in the placebo group the number of postmenopausal women with osteoporosis was unchanged, after 24 months. This post-hoc analysis is a proof-of concept study suggesting that genistein may be useful not only in postmenopausal osteopenia but also in osteoporosis. However, this proof-of concept study needs to be confirmed by a large, well designed, and appropriately focused randomized clinical trial in a population at high risk of fractures

Laser cleaning of gilded wood: a comparative study of colour variations induced by irradiation at different wavelengths

There is a growing interest by art conservators for laser cleaning of wood artworks, since traditional cleaning with chemical solvents can be a source of decay, due to the prolonged action of chemicals after the restoration. In this experiment we used excimer and Nd:YAG lasers, emitting radiation in the ultraviolet (248 nm), visible (532 nm) and near infrared (1064 nm), to investigate the effect of laser interaction on gilded wood samples at different wavelengths. Increasing fluence levels were tested to assess threshold values both for surface damage and colour changes. Detailed colorimetric analyses of the irradiated samples show that cleaning effectiveness is related to the emission wavelength, the fluence and the number of pulses