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Sample records for protect ovarian function

  1. Hydrogen-rich Water Exerting a Protective Effect on Ovarian Reserve Function in a Mouse Model of Immune Premature Ovarian Failure Induced by Zona Pellucida 3

    He, Xin; Wang, Shu-Yu; Yin, Cheng-Hong; Wang, Tong; Jia, Chan-Wei; Ma, Yan-Min

    2016-01-01

    Background: Premature ovarian failure (POF) is a disease that affects female fertility but has few effective treatments. Ovarian reserve function plays an important role in female fertility. Recent studies have reported that hydrogen can protect male fertility. Therefore, we explored the potential protective effect of hydrogen-rich water on ovarian reserve function through a mouse immune POF model. Methods: To set up immune POF model, fifty female BALB/c mice were randomly divided into four groups: Control (mice consumed normal water, n = 10), hydrogen (mice consumed hydrogen-rich water, n = 10), model (mice were immunized with zona pellucida glycoprotein 3 [ZP3] and consumed normal water, n = 15), and model-hydrogen (mice were immunized with ZP3 and consumed hydrogen-rich water, n = 15) groups. After 5 weeks, mice were sacrificed. Serum anti-Müllerian hormone (AMH) levels, granulosa cell (GC) apoptotic index (AI), B-cell leukemia/lymphoma 2 (Bcl-2), and BCL2-associated X protein (Bax) expression were examined. Analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) software. Results: Immune POF model, model group exhibited markedly reduced serum AMH levels compared with those of the control group (5.41 ± 0.91 ng/ml vs. 16.23 ± 1.97 ng/ml, P = 0.033) and the hydrogen group (19.65 ± 7.82 ng/ml, P = 0.006). The model-hydrogen group displayed significantly higher AMH concentrations compared with that of the model group (15.03 ± 2.75 ng/ml vs. 5.41 ± 0.91 ng/ml, P = 0.021). The GC AI was significantly higher in the model group (21.30 ± 1.74%) than those in the control (7.06 ± 0.27%), hydrogen (5.17 ± 0.41%), and model-hydrogen groups (11.24 ± 0.58%) (all P hydrogen group compared with that of the hydrogen group (11.24 ± 0.58% vs. 5.17 ± 0.41%, P = 0.021). Compared with those of the model group, ovarian tissue Bcl-2 levels increased (2.18 ± 0.30 vs. 3.01 ± 0.33, P = 0.045) and the Bax/Bcl-2 ratio decreased in the model-hydrogen group

  2. Tamoxifen and ovarian function.

    Martine Berliere

    Full Text Available BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II. All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol. Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year. All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year b: Oligomenorrhea (5 to 9 cycles/year c: Severe oligomenorrhea (1 to 4 cycles/year d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status

  3. Ovarian function after uterine artery embolisation

    2009-08-05

    Aug 5, 2009 ... Objective. To evaluate ovarian function in 29 patients who underwent uterine artery embolisation ... of FSH levels, kidney function, blood count and clotting time. .... Funding: Departmental funds and routine services in hospital;.

  4. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice.

    Jenna Kropp

    Full Text Available Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2-24 hours post-injection, Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the "infertility index" (quantifying the percentage of dams failing to achieve pregnancy through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health

  5. Identification of Novel Ovarian Cancer Oncogenes that Function by Regulating Exosome Function

    2017-09-01

    Novel Ovarian Cancer Oncogenes that Function by Regulating Exosome Function September 2017 x 1Sep2016...31Aug2017 Email: mbirrer@partners.org 6 Identification of Novel Ovarian Cancer Oncogenes that Function by Regulating Exosome Function xx

  6. Long-term function of ovarian tissue transplants

    Sherman J. Silber

    2012-12-01

    Full Text Available The long term duration of function of ovarian cortical tissue grafts is reviewed in this paper by describing cases of restoration of fertility by transplant of ovarian cortical tissue from matching donors where the recipient was in need of the transplant due to sterilizing effects of leukemia, premature ovarian failure (POF, and to reflect that it may be possible to postpone the normal time of menopause or to alleviate its symptoms.

  7. Radiations - induced disorders in ovarian function

    Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

    1988-01-01

    The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

  8. Benefits and risks of ovarian function and reproduction for cancer development and prevention.

    Schindler, Adolf E

    2011-12-01

    Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

  9. Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

    David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

    2017-07-01

    Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

  10. Long-term duration of function of ovarian tissue transplants

    Andersen, Claus; Silber, Sherman J; Berghold, Stinne Holm

    2012-01-01

    These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian...... or to alleviate its symptoms. These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had...

  11. Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.

    Jiaqiang Xiong

    Full Text Available Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx. For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now. In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes. Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs. Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs, and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.

  12. Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.

    Xiong, Jiaqiang; Lu, Zhiyong; Wu, Meng; Zhang, Jinjin; Cheng, Jing; Luo, Aiyue; Shen, Wei; Fang, Li; Zhou, Su; Wang, Shixuan

    2015-01-01

    Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.

  13. Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

    De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

    2017-10-01

    Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

  14. EFFECT OF NATURAL PLANT EXTRACTS ON PORCINE OVARIAN FUNCTIONS

    Attila Kádasi

    2015-02-01

    Full Text Available This report provides information about the impact of chosen natural plant extracts on basic ovarian functions. This article summarizes our results concerning the effect of selected plant extracts on proliferation, apoptosis and hormone secretion – release of progesterone (P4, testosterone (T and leptin (L on porcine granulosa cells (GC, We analyzed effects of ginkgo (GB, rooibos (RB, flaxseed (FL, green tea polyphenols (GTPP, green tea - epigallocatechin-3-gallate (EGCG, resveratrol (RSV and curcumin (CURC (0; 1; 10 and 100 μg.ml-1 on markers of proliferation, apoptosis and secretory activity of porcine ovarian granulosa cells by using immunocytochemistry and EIA. It was demonstrated, that all these natural plants and plant molecules inhibited the accumulation of proliferation-related peptide (PCNA and apoptosis-associated peptide (Bax in cultured. Furthermore, it was observed that natural plant extracts altered progesterone, testosterone and leptin release in porcine ovarian cells. It is concluded, that GB, RB, FL, RSV, CURC, GTPP and EGCG can directly affect ovarian cells and therefore they could potentially influence ovarian functions.

  15. Ovarian protection in cyclophosphamide-treated mice by fennel

    Azam Hassanpour

    Full Text Available Evaluation of protective effect of fennel on mouse ovary against the destructive effects of cyclophosphamide (CP was the aim of this study. Adult female NMARI mice were randomly divided into six groups (n = 8: (A negative control, (B CP200 mg/kg, (C fennel 400 mg/kg/day, (E, F, and D that received fennel 200, 400 and 100 mg/kg/day respectively + CP200 mg/kg. Their ovary weight, volume, and diameter (WVD were measured. Five micron sections were stained using the H&E method. The serum levels of oestrogen and progesterone were measured using ELISA kit. The results showed that WVD significantly reduced in the CP-treated groups in comparison with the A and C, but WVD increased after treatment of the mice with fennel extract, in comparison with B group. A significant decrease of serum in terms of oestrogen and progesterone levels among CP-treated groups in comparison with the A group was observed. In the CP-treated groups a reduction in the number of different ovarian follicles in comparison with the A and C groups was observed. However, in the treated animals with fennel extract, these parameters significantly increased in comparison with the B group. Finally, it is concluded that fennel can protect ovary from cyclophosphamide side effects. Keywords: Cyclophosphamide, Fennel, Mice, Ovary

  16. Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens.

    Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent; Kucuk, Omer

    2018-03-01

    Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( P Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( P lycopene-fed hens compared to control birds ( P lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

  17. The effects of buserelin microparticles on ovarian function in healthy ...

    The effects of buserelin microparticles on ovarian function in healthy women. ... A single-blind, randomised, parallel-group design was used to investigate the ... to at least 8 nmoVI (a sign of ovulation) and oestradiol concentrations increased to ...

  18. The non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function

    Guo Wenbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Yao Shuzhong

    2005-01-01

    Objective: To evaluate the effect of the non-target bi-ovarian branches occlusion in fibroids embolization on resumption of menses and ovarian function. Methods: The patients with the non-target bi-ovarian branches occlusion in uterine fibroids embolization (UFE) were classified into two groups, one for lipiodol deposited in bi-ovarian areas (Group A) , another for non lipiodol deposited in ovarian areas or in single ovarian area (Group B of non lipiodol deposited in bi-ovarian areas). The statistical difference between the data of group A and group B were assessed with Fisher test. All UFE were performed with the mixture of lipiodol and pingyangmycin. The serum level of Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were measured before UFE and 6 months after UFE. The statistical difference between the data of before and after UFE was assessed with t test. Results: Fifteen patients [age ranged 26-46 years, average (39.00 ± 5.62) years] had been followed up for an average (30.5±6.4) months (range 16-47 months). In 12 of 15, regular menses resumed after an average of (3.0 ±0.3) weeks (range 2-6 weeks). In 3 of 15 (20%), regular menses did not resume. The sexual hormone findings of menopause were found in three cases with amenorrhea after UFE. Amenorrhea was found in three cases with lipiodol deposited in bi-ovarian areas (Group A). Non-amenorrhea was found in the group of non-lipiodol deposited in bi-ovarian areas (Group B). There were significant statistical difference between Group A and Group B (P=0.002 19). Non amenorrhea was found in the patients aged over 45 years old. Three patients were found amenorrhea in the patients aged younger than 45 years old. There were no significant statistical difference between the serum level of FSH, LH and E2 before and 6 months after UFE (P>0.05). Conclusion: The incidence of amenorrhea is very high in the patients with lipiodol deposited in bi-ovarian areas when the bi-ovarian branches of

  19. Protective effect of oestradiol in the coeliac ganglion against ovarian apoptotic mechanism on dioestrus.

    Cynthia, Bronzi; Cristina, Daneri Becerra; Adriana, Vega Orozco; Belén, Delsouc María; María, Rastrilla Ana; Marilina, Casais; Zulema, Sosa

    2013-05-01

    The aims of this work were to investigate if oestradiol 10(-8)M in the incubation media of either the ovary alone (OV) or the ganglion compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system (a) modifies the release of ovarian progesterone (P4) and oestradiol (E2) on dioestrus II, and (b) modifies the ovarian gene expression of 3β-HSD and 20α-HSD enzymes and markers of apoptosis. The concentration of ovarian P4 release was measured in both experimental schemes, and ovarian P4 and E2 in the ex vivo system by RIA at different times. The expression of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and antiapoptotic bcl-2 and proapoptotic bax by RT-PCR were determined. E2 added in the coeliac ganglion caused an increase in the ovarian release of the P4, E2 and 3β-HSD, while in the ovary incubation alone it decreased P4 and 3β-HSD but increased and 20α-HSD and bax/bcl-2 ratio. It is concluded that through a direct effect on the ovary, E2 promotes luteal regression in DII rats, but the addition of E2 in the coeliac ganglion does not have the same effect. The peripheral nervous system, through the superior ovarian nerve, has a protective effect against the apoptotic mechanism on DII. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Endocrinologic control of normal canine ovarian function.

    Concannon, P W

    2009-07-01

    regression after day 20 to 30 involves periodic cell death, diminution in cell size, low levels of apoptosis and minimal or modest involvement of endogenous prostaglandin F (PGF) production. The canine corpus luteum (CL) is dependent on both LH and prolactin as stimulating luteotrophins by day 15, and as required luteotrophins by days 20-25, if not earlier. Thereafter, both luteotrophins likely have cellular mechanisms of action similar to those reported for other species. Progesterone secretion during pregnancy is greatly enhanced by characteristic, and probably relaxin-stimulated, increases in prolactin concentration starting at or after day 25, and persisting to term. Near term, foetoplacental maturation results in the placental release of large, luteolytic amounts of PGF for 1-2 days pre-partum. Pre-partum luteolysis, like that induced by exogenous prostaglandin, likely involves a cascade enhanced by the removal of progesterone inhibition of PGF release and some degree of intra-luteal PGF synthesis. That a likely twofold or greater increase in progesterone production by the CL of pregnancy does not result in significantly higher serum progesterone than in non-pregnant metoestrus relates to several biological changes, including a large increase in plasma volume of distribution, increased metabolism of progesterone by increased uterine, placental and mammary masses and increased liver clearance and excretion of progesterone and progesterone metabolite. Anoestrus length and ovarian cycle intervals, variable within and among bitches, are likely affected by neuroendocrine components of an endogenous circannual cycle, albeit only photo-entrained in the Basenji breed. This may be modified by the prior luteal phase, exposure to oestrus female pheromones and as yet unknown mechanisms that likely operate via inhibitory opioidergic and/or stimulatory dopaminergic hypothalamic pathways affecting late anoestrus increases in LH.

  1. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Camats, N.; Garcia, F.; Parrilla, J.J.; Calaf, J.; Martin-Mateo, M.; Caldes, M. Garcia

    2009-01-01

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F 0 ) with reproductive parameters, and in the somatic cells of the resulting foetuses (F 1 ) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  2. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  3. Direct effect of curcumin on porcine ovarian cell functions.

    Kádasi, Attila; Maruniaková, Nora; Štochmaľová, Aneta; Bauer, Miroslav; Grossmann, Roland; Harrath, Abdel Halim; Kolesárová, Adriana; Sirotkin, Alexander V

    2017-07-01

    Curcuma longa Linn (L.) is a plant widely used in cooking (in curry powder a.o.) and in folk medicine, but its action on reproductive processes and its possible mechanisms of action remain to be investigated. The objective of this study was to examine the direct effects of curcumin, the major Curcuma longa L. molecule, on basic ovarian cell functions such as proliferation, apoptosis, viability and steroidogenesis. Porcine ovarian granulosa cells were cultured with and without curcumin (at doses of 0, 1, 10 and 100μg/ml of medium). Markers of proliferation (accumulation of PCNA) and apoptosis (accumulation of bax) were analyzed by immunocytochemistry. The expression of mRNA for PCNA and bax was detected by RT-PCR. Cell viability was detected by trypan blue exclusion test. Release of steroid hormones (progesterone and testosterone) was measured by enzyme immunoassay (EIA). It was observed that addition of curcumin reduced ovarian cell proliferation (expression of both PCNA and its mRNA), promoted apoptosis (accumulation of both bax and its mRNA), reduced cell viability, and stimulated both progesterone and testosterone release. These observations demonstrate the direct suppressive effect of Curcuma longa L./curcumin on female gonads via multiple mechanisms of action - suppression of ovarian cell proliferation and viability, promotion of their apoptosis (at the level of mRNA transcription and subsequent accumulation of promoters of genes regulating these activities) and release of anti-proliferative and pro-apoptotic progesterone and androgen. The potential anti-gonadal action of curcumin should be taken into account by consumers of Curcuma longa L.-containing products. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Spontaneous Ovarian Pregnancy and Over Protective Management: A Case Report

    Hatice Ender Soydinç

    2016-05-01

    Full Text Available We aimed to present a case of primary ovarian pregnancy in a 31-year-old patient who presented to the emergency room with symptoms and signs of acute abdomen and positive beta HCG test. A gestation sac of 6 weeks was detected in the right ovary by transvaginal sonography. Emergency laparotomy and extirpation of the ectopic tissue was performed.

  5. The Brain as a Target for Environmental Toxicants that alter Ovarian Function.

    In this review we discuss the ovarian cycle of the laboratory rat in order to familiarize the reader with the well-understood timing of the neuroendocrine events controlling ovarian function. This is followed by a discussion of the location and function of the estrogen and proges...

  6. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  7. Ovarian function following pelvic irradiation in prepubertal and pubertal girls and young adult women

    Schuck, A.; Hamelmann, V.; Braemswig, J.H.

    2005-01-01

    Purpose: To analyze the effect of pelvic radiotherapy on ovarian function in prepubertal and pubertal girls and young adult women. Patients and methods: In a retrospective monoinstitutional analysis, patients 15 Gy to the ovaries developed hormone failure. In one case of a patient receiving an ovarian dose of 15 Gy, hormone failure was not found. In case of pelvic irradiation excluding at least one ovary, approximately half of the patients developed ovarian dysfunction, probably also due to the effects of polychemotherapy. (orig.)

  8. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

    Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2012-01-01

    To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

  9. Skeletal Muscle Mitochondrial Function in Polycystic Ovarian Syndrome

    Rabøl, Rasmus; Svendsen, Pernille Maj; Skovbro, Mette

    2011-01-01

    Hyperinsulinemic euglycemic clamps (40 mU/min/m2) and muscle biopsies were performed on 23 women with PCOS (9 lean (body mass index (BMI) 25 kg/m2)) and 17 age- and weight-matched controls (6 lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function. Results......Objective Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance, which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry. Methods...... Insulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mtDNA/genomicDNA. We found no correlation between...

  10. Hypoandrogenism in association with diminished functional ovarian reserve.

    Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

    2013-04-01

    Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age women with DOR, defined as women age >40 years. Forty-nine control patients women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels. While results support lower androgen levels in women with DOR, and even more so in women with POA/OPOI, presented data should be viewed as preliminary, considering the known variability of androgen levels and the small number of women in whom morning cortisol levels were available. Especially at young ages DFOR appears associated with significant hypoandrogenism (low T) in

  11. Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice

    David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

    2016-01-01

    Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscl...

  12. Ovarian and Uterine Functions in Female Survivors of Childhood Cancers.

    Oktem, Ozgur; Kim, Samuel S; Selek, Ugur; Schatmann, Glenn; Urman, Bulent

    2018-02-01

    Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer. Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation

  13. Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

    Anderson, Richard A; Rosendahl, Mikkel; Kelsey, Thomas W

    2013-01-01

    Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.......Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea....

  14. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

    Lambertini, Matteo; Cinquini, Michela; Moschetti, Ivan; Peccatori, Fedro A; Anserini, Paola; Valenzano Menada, Mario; Tomirotti, Maurizio; Del Mastro, Lucia

    2017-01-01

    The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

    Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

    1998-11-01

    We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

  16. Effect of antitubercular treatment on ovarian function in female genital tuberculosis with infertility

    Jai Bhagwan Sharma

    2016-01-01

    Full Text Available AIM: To evaluate the effect of antitubercular therapy (ATT on an ovarian function such as ovarian reserve, ovarian dimensions, and ovarian stromal blood flow. SETTINGS AND DESIGN: Prospective study design. MATERIALS AND METHODS: Fifty infertile women with female genital tuberculosis (FGTB without tubo-ovarian masses diagnosed by positive acid-fast bacilli culture or epithelioid granuloma on endometrial aspirate or positive polymerase chain reaction with positive findings on laparoscopy or hysteroscopy were recruited. The ovarian function tests were performed on day 2/3 as follicle-stimulating hormone (FSH levels and anti-Mullerian hormone (AMH levels. Ovarian dimensions (length, width, and depth were measured using a transvaginal ultrasound. Mean antral follicle count (AFC and ovarian stromal blood flow (peak systolic velocity [PSV], pulsatility index (PI, and resistive index [RI] were measured using a transvaginal ultrasound. All women were started on ATT for 6 months by directly observed treatment strategy. After completion of ATT, all the parameters were repeated. RESULTS: There was a significant increase in AMH (2.68 ± 0.97 ng/ml to 2.8 ± 1.03 ng/ml pre- to post-ATT, nonsignificant increase in FSH (7.16 ± 2.34 mIU/ml to 7.26 ± 2.33 mIU/ml post-ATT, significant increase in mean AFC (7.40 ± 2.12-8.14 ± 2.17, PSV in the right ovary (6.015-6.11 cm/s and left ovary (6.05-6.08 cm/s, PI in the right ovary (0.935-0.951 cm/s and left ovary (0.936-0.957 cm/s, and RI in the right ovary (0.62 ± 0.01-0.79 ± 0.02 and left ovary (0.65 ± 0.02-0.84 ± 0.01 with ATT. There was no significant change in mean ovarian dimensions (ovarian length, breadth, and width and summed ovarian volume with ATT. On laparoscopy, tubercles were seen in 27 (54% women. Caseous nodules and encysted ascites were seen in 8% cases each. CONCLUSION: ATT improves the ovarian function (AMH and AFC and ovarian blood flow in women with FGTB.

  17. Function of ovarian tissue after long-term storage.

    Lieberman, Brian

    2012-08-01

    Ovarian tissue cryopreservation is one of the options available to preserve fertility in cancer patients and to allow them to conceive when they have overcome their primary disease. The publication of a report by Anderson and colleagues documenting live births in three women arising from ovarian cortical strips that had been transplanted more than 7 years previously represents an apparent further advance in this field. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

    Martin Ligr

    Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

  19. Age-independent anti-Müllerian hormone (AMH) standard deviation scores to estimate ovarian function.

    Helden, Josef van; Weiskirchen, Ralf

    2017-06-01

    To determine single year age-specific anti-Müllerian hormone (AMH) standard deviation scores (SDS) for women associated to normal ovarian function and different ovarian disorders resulting in sub- or infertility. Determination of particular year median and mean AMH values with standard deviations (SD), calculation of age-independent cut off SDS for the discrimination between normal ovarian function and ovarian disorders. Single-year-specific median, mean, and SD values have been evaluated for the Beckman Access AMH immunoassay. While the decrease of both median and mean AMH values is strongly correlated with increasing age, calculated SDS values have been shown to be age independent with the differentiation between normal ovarian function measured as occurred ovulation with sufficient luteal activity compared with hyperandrogenemic cycle disorders or anovulation associated with high AMH values and reduced ovarian activity or insufficiency associated with low AMH, respectively. These results will be helpful for the treatment of patients and the ventilation of the different reproductive options. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Ovarian function and growth performance of indigenous goats in Malaysia

    Adnan, S.; Jainudeen, M.R.; Alimon, A.R.; Sharifuddin, W.

    1991-01-01

    Ovarian activity and factors influencing it were studied in the Malaysian indigenous goat using plasma progesterone radioimmunoassay technique and laparoscopic examination of the ovaries. Laparoscopy, complemented by progesterone assay, was found to be a reliable technique for diagnosing the presence of corpora lutea (CL). However, progesterone assay had the limitation that it could not detect the presence of early developing CL. Two morphological types of CL were observed, either protruding or embedded. The mean plasma progesterone concentrations for pregnant, dioestrous and postpartum anoestrous goats were 4.8 ± 0.72, 4.7 ± 1.60 and <0.7 ng/mL respectively. An inhibitory effect of suckling on the resumption of postpartum ovarian activity was also observed. Removal of kids tended to hasten the onset of postpartum ovarian activity. Continuous confinement of goats was suspected to contribute to conception failure and non-regression of the CL. Kids fed improved diet showed higher average daily weight gain than those suckling their dams. (author). 12 refs, 3 figs, 7 tabs

  1. The effect of functional status of the ovaries on the embryological results of controlled ovarian hyperstimulation

    Grzegorz Mrugacz

    2013-12-01

    Full Text Available Introduction: Controlled ovarian hyperstimulation is an integral part of infertility treatment. Despite many years of use, some aspects of controlled ovarian stimulation have not yet been clarified, especially the role of the functional status of the ovaries before hormonal stimulation. Aim of the research: To assess the effect of the functional status of the ovaries on the embryological results of controlled ovarian hyperstimulation. Material and methods: The retrospective study included female patients treated for infertility. The patients were divided into two groups depending on the ultrasonographic appearance of the ovaries before controlled ovarian hyperstimulation. Patients with small antral follicles 0.05. The numbers of A, C, D quality embryos were comparable between the groups (p > 0.05. There were more B quality embryos in group I than II (p > 0.05. The embryo growth rate was significantly faster in group I than II. Conclusions: The results of the present study indicate that the functional status of the ovaries before controlled ovarian hyperstimulation plays a pivotal role in treatment outcome.

  2. Effect of uterine arterial embolization on the ovarian function in puerpera with postpartum hemorrhage

    Yan-Xian Deng

    2017-06-01

    Full Text Available Objective: To observe the hemostatic effect of uterine arterial embolization in the treatment of postpartum hemorrhage and the effect on menstruation, sex hormone level, ovarian function, and pelvic floor function. Methods: A total of 45 patients with postpartum hemorrhage who were admitted in the Department of Obstetrics of our hospital from January, 2014 to June, 2016 for uterine arterial embolization were included in the study and served as the treatment group. The postoperative menstruation recovery was recorded. The hormone levels, ovarian function, and pelvic floor function before and after treatment were recorded. A total of 42 normal puerpera were served as the control group. The menstrual status of the two groups after menstruation was compared. Results: Rapid and effective hemostasis could be obtained from patients in the treatment group after treatment with hemostasis success rate of 100%. The comparison of menstruation cycle and menstruation days after treatment between the two groups was not statistically significant. The levels of E2, P, FSH, LH and PRL, ovarian function index RI and PI, pelvic floor muscle fatigue and vaginal dynamic pressure before and after 3 and 6 months had no significant difference, and there was no significant difference between the 2 groups. Conclusions: Uterine arterial embolization in the treatment of postpartum hemorrhage is effective, and has no influence on the patient's menstrual conditions, sex hormone levels, ovarian and pelvic floor functions; therefore, it is worthy of clinical application.

  3. Ovarian function's role during cancer cachexia progression in the female mouse.

    Hetzler, Kimbell L; Hardee, Justin P; LaVoie, Holly A; Murphy, E Angela; Carson, James A

    2017-05-01

    Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The Apc Min/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female Apc Min/+ mouse. Our study of ovarian reproductive function in female Apc Min/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female Apc Min/+ mice. Copyright © 2017 the American Physiological Society.

  4. Ovarian function following pelvic irradiation in prepubertal and pubertal girls and young adult women

    Schuck, A.; Hamelmann, V. [University Hospital Muenster (Germany). Dept. of Radiotherapy; Braemswig, J.H. [University Hospital Muenster (DE). Dept. of Pediatrics] [and others

    2005-08-01

    Purpose: To analyze the effect of pelvic radiotherapy on ovarian function in prepubertal and pubertal girls and young adult women. Patients and methods: In a retrospective monoinstitutional analysis, patients <30 years of age at diagnosis were included who had been irradiated between 1979 and 1998. The main tumor types were Hodgkin's disease (38%), Erwing's sarcoma (20%) and nephroblastoma (11%). Patients were classified into three groups according to the position of the ovary in relation to the radiation portals. Group 1 was defined by direct irradiation of both ovaries. Group 2 patients were included with both ovaries potentially located in the radiation portals. In group 3, at least one ovary was not directly irradiated. The median follow-up was 128 months. Results: 16 of 55 analyzed patients were categorized in group 1. In ten of these patients, hormone status was evaluable. The ovarian doses were {>=}15 Gy. Except for one patient treated with 15 Gy all developed hormone failure. Eight of 14 patients of group 2 were evaluable. Seven of these patients developed ovarian failure. 19 of 24 patients in group 3 were evaluable. Nine of these patients developed ovarian failure. The observed difference in the rate of ovarian failure between the groups is statistifcally significant (p=0.045). Conclusion: All patients receiving >15 Gy to the ovaries developed hormone failure. In one case of a patient receiving an ovarian dose of 15 Gy, hormone failure was not found. In case of pelvic irradiation excluding at least one ovary, approximately half of the patients developed ovarian dysfunction, probably also due to the effects of polychemotherapy. (orig.)

  5. Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

    Uçar, Semra; Pandir, Dilek

    2017-11-01

    In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

  6. Is there a declining trend in ovarian function among infertility clinic patients?

    Sobek Jr., A.; Tkadlec, Emil; Hladíková, B.; Sobek, A.

    2010-01-01

    Roč. 25, č. 1 (2010), s. 127-132 ISSN 0268-1161 Institutional research plan: CEZ:AV0Z60930519 Keywords : ovarian function * decrease * infertility * IVF Subject RIV: FK - Gynaecology, Childbirth Impact factor: 4.357, year: 2010

  7. Effects of a preovulatory single low dose of mifepristone on ovarian function

    van der Stege, Jolande G.; Pahl-van Beest, Elske H.; Beerthuizen, Rob J. C. M.; van Lunsen, Rik H. W.; Scholten, Piet C.; Bogchelman, Dick H.

    Objectives To investigate the effect of a single low dose of mifepristone on ovarian function, when administered in the preovulatory period. Methods Healthy women with regular menstrual cycles were studied during two consecutive menstrual cycles. Either mifepristone or placebo was given in a

  8. Premature aging of cardiovascular/platelet function in polycystic ovarian syndrome.

    Chan, Wai Ping A; Ngo, Doan T; Sverdlov, Aaron L; Rajendran, Sharmalar; Stafford, Irene; Heresztyn, Tamila; Chirkov, Yuliy Y; Horowitz, John D

    2013-07-01

    The objective of this study was to compare the impact of aging on nitric oxide (NO) modulation of platelet and vascular function in healthy women and women with polycystic ovary syndrome. A case-control study of women ages 18 to 60 years, comparing women with polycystic ovarian syndrome against age-matched healthy controls, was performed. A total of 242 women, of whom 109 had polycystic ovarian syndrome (based on Rotterdam criteria), participated in the study. Women who were pregnant or on clopidogrel were excluded from the study. Inhibition of platelet aggregation by nitric oxide (primary outcome measure), vascular endothelial function, plasma concentrations of N(G), N(G)-dimethyl-L-arginine (ADMA), endothelial progenitor cell count, and high-sensitivity C-reactive protein (markers of endothelial dysfunction and inflammation) were assessed. With increasing age in control women, there was progressive attenuation of platelet responses to NO, impairment of endothelial function, and elevation of ADMA levels (P ≤.001). Irrespective of age, women with polycystic ovarian syndrome exhibited greater impairment of all these parameters (all P polycystic ovarian syndrome, these changes are present from early adult life and may contribute to premature atherogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Ovarian transfer following irradiation as an alternative to restore reproductive functions

    Salgado, Andreia Ruis; Passos, Luiz Augusto Correa; Ginemes, Ana Paula; Dias, Viviane Liotti [Universidade Estadual de Campinas, SP (Brazil). Centro Multidisciplinar para a Investigacao Biologica (CEMIB/UNICAMP)], e-mail: viviliotti@cemib.unicamp.br; Spencer, Patrick Jack; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Assisted reproduction technologies are essential for restoring reproductive functions, especially in ovary cancer cases, which besides impairing fertility; present the highest lethality amongst gynecological diseases. Classical treatment involves surgery, radiotherapy and chemotherapy, and in young women, the recommended treatment is the removal of the affected ovary, leading to physical, psychological and emotional problems. An alternative would be the ovarian transfer after the treatment. However, there are no data in the literature about experiments specifically designed to investigate the interference of this procedure on reproductive functions. In the present work, we used the C57BL/6Unib and B6CF1 hybrid mice strains to evaluate the viability of ovarian transfer before and after irradiation, as well as possible differences in radiosensitivity between the strains. To do so, female mice from both strains were irradiated with 4 Gy and submitted to either partial or total ovarian transfer form healthy donors. After the surgery, the animals were mated and the results obtained so far for mating 7 days after the procedure indicate that irradiation promoted a significant decrease in fertility (p=0.0127). Also, our data show that the recovery of fertility is proportional to the amount of grafted ovarian tissue. Furthermore, there seems to be differences in radiosensitivity, from genetic origin, between the two mice strain, since, after irradiation, the hybrid mice had bigger litters than the donor strain. (author)

  10. Ovarian transfer following irradiation as an alternative to restore reproductive functions

    Salgado, Andreia Ruis; Passos, Luiz Augusto Correa; Ginemes, Ana Paula; Dias, Viviane Liotti; Spencer, Patrick Jack; Nascimento, Nanci do

    2009-01-01

    Assisted reproduction technologies are essential for restoring reproductive functions, especially in ovary cancer cases, which besides impairing fertility; present the highest lethality amongst gynecological diseases. Classical treatment involves surgery, radiotherapy and chemotherapy, and in young women, the recommended treatment is the removal of the affected ovary, leading to physical, psychological and emotional problems. An alternative would be the ovarian transfer after the treatment. However, there are no data in the literature about experiments specifically designed to investigate the interference of this procedure on reproductive functions. In the present work, we used the C57BL/6Unib and B6CF1 hybrid mice strains to evaluate the viability of ovarian transfer before and after irradiation, as well as possible differences in radiosensitivity between the strains. To do so, female mice from both strains were irradiated with 4 Gy and submitted to either partial or total ovarian transfer form healthy donors. After the surgery, the animals were mated and the results obtained so far for mating 7 days after the procedure indicate that irradiation promoted a significant decrease in fertility (p=0.0127). Also, our data show that the recovery of fertility is proportional to the amount of grafted ovarian tissue. Furthermore, there seems to be differences in radiosensitivity, from genetic origin, between the two mice strain, since, after irradiation, the hybrid mice had bigger litters than the donor strain. (author)

  11. Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.

    Berga, Sarah L; Marcus, Marsha D; Loucks, Tammy L; Hlastala, Stefanie; Ringham, Rebecca; Krohn, Marijane A

    2003-10-01

    To determine whether cognitive behavior therapy (CBT) targeted to problematic attitudes common among women with functional hypothalamic amenorrhea would restore ovarian function. Randomized, prospective, controlled intervention. Clinical research center in an academic medical institution. Sixteen women participated who had functional hypothalamic amenorrhea; were of normal body weight; and did not report psychiatric conditions, eating disorders, or excessive exercise. Subjects were randomized to CBT or observation for 20 weeks. Serum levels of E(2) and P and vaginal bleeding were monitored. Of eight women treated with CBT, six resumed ovulating, one had partial recovery of ovarian function without evidence of ovulation, and one did not display return of ovarian function. Of those randomized to observation, one resumed ovulating, one had partial return of ovarian function, and six did not recover. Thus, CBT resulted in a higher rate of ovarian activity (87.5%) than did observation (25.0%), chi(2) = 7.14. A cognitive behavioral intervention designed to minimize problematic attitudes linked to hypothalamic allostasis was more likely to result in resumption of ovarian activity than observation. The prompt ovarian response to CBT suggests that a tailored behavioral intervention offers an efficacious treatment option that also avoids the pitfalls of pharmacological modalities.

  12. Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

    Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin

    2014-01-01

    OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls.DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born...... in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown.CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19....

  13. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin.

    Stephanie Morgan

    Full Text Available Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001 and doxorubicin (3 fold, p<0.01. TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01 but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s the patient is exposed to.

  14. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

    Liying Gu

    Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

  15. Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.

    Maurizio Chiriva-Internati

    Full Text Available Sperm protein (Sp17 is an attractive target for ovarian cancer (OC vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17 was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

  16. Posterior pelvic exenteration and retrograde total hysterectomy in patients with locally advanced ovarian cancer: Clinical and functional outcome

    Roberto Berretta

    2016-06-01

    Conclusion: Our study confirmed that pelvic posterior exenteration associated with retrograde radical hysterectomy represents the safest radical surgical approach to advanced ovarian cancer, which permits preservation of the pelvic autonomic nerve plexus and, therefore, bladder and colorectal functions.

  17. Rate and Time of Ovarian Function Restoration in Menopausal Breast Cancer Patients Who Received Letrozole Following Chemotherapy

    Shapour Omidvari

    2015-01-01

    Full Text Available Background: The present study aimed to investigate the rate and time of ovarian function restoration in breast cancer patients between 40 and 60 years of age who were in menopause (biochemically documented and received letrozole after chemotherapy. We intended to further clarify the management strategy for breast cancer patients with different menopausal status. Methods: We prospectively measured the effects of replacing tamoxifen with letrozole on ovarian function recovery in 90 women from two age groups (40-50 and 51-60 years. All had breast cancer and were treated by chemotherapy. Patients had laboratory documentation of menopause (FSH >40 mIU/ml and estradiol <20 pg/mL. Patients did not have menstruation for at least one year. Study patients received letrozole. At three month intervals, we checked their FSH and estradiol levels. Results:At three months after beginning letrozole, 12 patients in the younger age group had laboratory ovarian function restoration, among which three had vaginal bleeding. In the older group, 8 patients had increased estradiol levels; however, there was no evidence of vaginal bleeding in this group. At 6, 9 and 12 months, no ovarian function restoration was seen in the older group. However in younger patients, 4 had laboratory evidence of ovarian function restoration at 6 months, 2 at 9 months and 1 patient showed laboratory ovarian function restoration at 12 months of follow-up. Totally, there was a significant difference in the occurrence of ovarian function restoration between the two groups (P=0.03. Conclusion: A remarkable portion of women with chemotherapy-induced amenorrhea may develop ovarian function restoration. Therefore, endocrine therapy using aromatase inhibitors in patients with chemotherapy-induced amenorrhea should be followed by a regular hormonal study.

  18. Feed intake alters immune cell functions and ovarian infiltration in broiler hens: implications for reproductive performance.

    Liu, Zu-Chen; Xie, Yi-Lun; Chang, Chai-Ju; Su, Chia-Ming; Chen, Yu-Hui; Huang, San-Yuan; Walzem, Rosemary L; Chen, Shuen-Ei

    2014-06-01

    Leukocytes are known to participate in ovarian activities in several species, but there is a surprising lack of information for the common chicken. Broiler hens consuming feed ad libitum (AL) exhibit a number of ovarian irregularities, but leukocyte functions are unstudied. In contrast to feed-restricted (R) hens, AL feeding for 7 wk significantly reduced egg production and clutch length while increasing pause length and atretic follicle numbers (P hens contained less progesterone, and follicle walls were thicker with loose fibrous morphology and had less collagenase-3-like gelatinolytic activity but more IL-1beta (P hen peripheral heterophils and monocytes (P hens. © 2014 by the Society for the Study of Reproduction, Inc.

  19. Manipulation of Ovarian Function Significantly Influenced Sarcopenia in Postreproductive-Age Mice

    Rhett L. Peterson

    2016-01-01

    Full Text Available Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.

  20. Ovarian steroid sulphate functions as priming pheromone in male ...

    Unknown

    The study reveals that pre-ovulatory females of the fish Barilius bendelisis (Ham.) release sex steroids and their conjugates into the water and that a steroid sulphate of these compounds functions as a potent sex pheromone which stimulates milt production in conspecific males prior to spawning. Since males exposed to the ...

  1. Acupuncture attenuates hyperglycaemia and improves ovarian function in female rats subjected to continuous light exposure.

    Kang, Xuezhi; Jia, Lina; Li, Yaming; Zhang, Xu

    2017-10-01

    Exposure to unnatural light cycles is increasingly associated with obesity and the metabolic syndrome. The purpose of this study was to examine the effects of electroacupuncture (EA) on glucose metabolism and ovarian function in female rats subjected to long-term continuous light exposure. Female Sprague-Dawley rats (n=24) were divided into three experimental groups: an LD group that was maintained under a normal light-dark cycle (healthy control); an LL group that was exposed to continuous light for 21 weeks but remained untreated; and an LL+EA group that received EA at ST36 and SP6 during weeks 17 to 21 of continuous light exposure. Oestrous cycles of female rats kept in a continuously lit environment for 21 weeks were disordered and polycystic ovarian syndrome (PCOS)-like changes occurred, accompanied by increased fasting blood glucose (6.23±0.33 vs 5.27±0.40 mmol/L in week 17, p=0.015) and reduced fasting levels of serum testosterone (0.07±0.018 vs 0.12±0.058 ng/L, p=0.043) and insulin (0.89±0.20 vs 1.43±0.46 ng/L, p=0.006). After 5 weeks of EA treatment at ST36 and SP6, ovarian cycle disruption was mitigated and blood glucose levels showed a gradual decline (5.18±0.37 vs 5.80±0.55 mmol/L, p=0.017; and 5.73±0.31 vs 6.62±0.13 mmol/L, p=0.004; in the fourth and fifth weeks of EA treatment, respectively). EA also attenuated the reductions otherwise seen in serum insulin and testosterone levels. Prolonged exposure to light can lead to a decline in ovarian and pancreatic function. EA at ST36 and SP6 may reduce abnormally elevated blood glucose levels and improve ovarian and pancreatic hormone levels. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. [Age-related characteristics of structural support for ovarian function].

    Koval'skiĭ, G B

    1984-12-01

    Histoenzymological assay was used to investigate various structures of the ovaries of rats of two groups aged 3-4 and 12-14 months during estral cycle. The activity of 3 beta-, 17 beta- and 20 alpha-steroid dehydrogenases, glucose-6-phosphate dehydrogenase, NAD and NADP-diaphorases, esterase, acid and alkaline phosphatases was studied. It has been shown that transport alterations in the microcirculation including the hematofollicular barrier play, the leading part in age-dependent depression of reproductive and endocrine functions. Ageing rats demonstrated no linkage between endothelial, thecal and granular cells, which points to the injury of the histophysiological mechanisms of the follicular system integration.

  3. Anti-Müllerian Hormone as a Sensitive Marker of Ovarian Function in Young Cancer Survivors

    Maryna Krawczuk-Rybak

    2013-01-01

    Full Text Available We evaluated ovarian function by measuring the levels of anti-Müllerian hormone (AMH, estradiol, and gonadotropins in 83 young women treated for cancer during childhood and adolescence, and classified according to post-treatment gonadal toxicity versus 38 healthy females. Results. The mean AMH values were lower in the entire cohort independently of the risk group as compared to the control, whereas FSH was elevated only in the high risk group. The lowest AMH values were noted in patients after bone marrow transplantation (BMT and those treated for Hodgkin lymphoma (HL. Nineteen patients (22.9% had elevated FSH. They all had low AMH values. Lowered AMH values (but with normal FSH and LH were observed in 43 patients (51.8%. There was no effect of age at the time of treatment (before puberty, during or after puberty on AMH levels. Conclusion. Our results show the utility of AMH measurement as a sensitive marker of a reduced ovarian reserve in young cancer survivors. Patients after BMT and patients treated for HL, independently of age at treatment (prepuberty or puberty, are at the highest risk of gonadal damage and early menopause.

  4. Association between the location of transposed ovary and ovarian function in patients with uterine cervical cancer treated with (postoperative or primary) pelvic radiotherapy.

    Hwang, Jong Ha; Yoo, Heon Jong; Park, Sae Hyun; Lim, Myong Cheol; Seo, Sang-Soo; Kang, Sokbom; Kim, Joo-Young; Park, Sang-Yoon

    2012-06-01

    To evaluate the effectiveness of ovarian transposition procedures in preserving ovarian function in relation to the location of the transposed ovaries in patients who underwent surgery with or without pelvic radiotherapy. Retrospective. Uterine cancer center. A total of 53 patients with cervical cancer who underwent ovarian transposition between November 2002 and November 2010. Ovarian transposition to the paracolic gutters with or without radical hysterectomy and lymph node dissection. Preservation of ovarian function, which was assessed by patient's symptoms and serum FSH level. Lateral ovarian transposition was performed in 53 patients. Based on receiver operator characteristic curve analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest was significantly associated with preservation of ovarian function after treatment (area under receiver operator characteristic curve: 0.757, 95% confidence interval [CI]: 0.572-0.943). In univariate analysis, higher location of transposed ovary more than 1.5 cm from the iliac crest was the only independent factor for intact ovarian function (odds ratio 9.91, 95% CI: 1.75-56.3). Multivariate analysis confirmed that the location of transposed ovary (odds ratio 11.72, 95% CI 1.64-83.39) was the most important factor for intact ovarian function. Location of transposed ovary higher than 1.5 cm above the iliac crest is recommended to avoid ovarian failure after lateral ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical cancer. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited

    Ehrmann, David A.

    2016-01-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989–1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired

  6. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

    Rosenfield, Robert L; Ehrmann, David A

    2016-10-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity

  7. The Protective effect of Ellagic acid on rats’ ovarian fetus toxicity induced by cyclophosphamide

    M Mousavi M

    2015-10-01

    Full Text Available Background & aim: Cyclophosphamide, an alkylating agent used in the treatment of cancer that has many side effects on different organs, including the gonads .The purpose of this study was to investigate the effects of an antioxidant Ellagic acid on cyclophosphamide -induced toxicity in rat fetal ovarian tissue. Methods: Forty two pregnant  female Wistar rats weighing 250-200 gr were randomly divided into seven groups.The first, second, third, fourth, fifth and sixth 5 mg/ kg cyclophosphamide on days 1, 13 and 18 were given intraperitoneal remote pregnancy .The fourth, fifth and sixth groups hour after receiving cyclophosphamide, Ellagic acid (10 mg/kg has received in the course of pregnancy.Control groups and seven group (normal during pregnancy daily orally received 0.5 mL of saline. After postpartum, Neonatal rats were anesthetized with ether. Animals were dissects, then Ovaries were removed and transferred to 10% formalin solution. After tissue processing, tissue sections were prepared and H&E stained.Data were analyzed by SPSSsoftware and One- way ANOVA test. Results: The groups that were exposed to cyclophosphamide ovarian mean of diameter, primordial follicle diameter and number of follicular cell of primordialin control group compared to ellagic acid treatments showed a significant decrease. Conclusion: The results showed that Ellagic acid due to its antioxidant properties could reduce the harmful effects caused by cyclophosphamide in the fetal ovary.

  8. Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study

    Rosendahl, M.; Andersen, Claus Yding; Ernst, E.

    2008-01-01

    menstruation was shown to be a good indicator of ovarian function. The cryopreservation procedure rarely complicated cancer treatment (5%) and 84% felt comforted because they had potentially secured their fertility. CONCLUSIONS: Cryopreservation of ovarian tissue should be considered in young female patients...

  9. The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function in the Guinea pig

    Zarkawi, M.; Galbraith, H.

    1992-01-01

    The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function was investigated in the Guinea pig. Certain comparisons were made with testosterone, the naturally occurring androgen, administered as the phenylpropionate ester. Progesterone was analysed using radioimmunoassay. two milligrams trenbolone acetate per Kg given subcutaneously on alternate days for 20 days blocked oestrous cyclicity and ovulation in 9 of 10 animals. A similar effect was shown by 2.2 mg of testosterone phenylpropionate. Treatment of trenbolone acetate-treated animals with exogenous gonadotropins suggested that the production of follicle stimulating hormone had been suppressed. Signs of abnormality were seen in the livers of animals receiving 2 mg trenbolone acetate and 2.2 mg testosterone phenylpropionate. (author). 17 refs., 2 tabs

  10. The camp analogue, dbcAMP can stimulate rabbit reproductive functions: I. Effect on ovarian folliculogenesis, ovulation and embryo production

    Chrenek P.

    2012-01-01

    Full Text Available The aim of our study was to examine the influence of administration of N6,2’-dibutyryladenosine 3’5’-cyclic monophosphate (dbcAMP, a cAMP agonist, on ovarian folliculogenesis and atresia, as well as on reproductive efficiency in rabbits, whose ovarian cycle and ovulation was induced by gonadotropins. Ovarian cycle and ovulation of control rabbits were induced by 20 IU/kg PMSG followed by 35 IU/kg hCG administration. Experimental animals received PMSG and hCG together with dbcAMP (at 5, 25 or 50 μg/animal. After ovulation and insemination, the animals were sacrificed. Ovaries were weighted, histological sections of ovaries were prepared, and the presence of ovulated and not ovulated follicles and different stages of atresia was evaluated by light microscopy. The eggs were flushed from the oviducts after insemination and cultured up to blastocyst cell stage. Numbers of ovarian Corpora lutea, ovulated oocytes and oocyte-derived zygotes and embryos reaching hatched blastocyst stage were determined. Administration of dbcAMP (at doses 25 or 50 μg/animal, but not at 5 μg/animal was able to increase the proportion of follicles with cystic and luteinization-related atresia. Furthermore, dbcAMP (50 μg/animal, but not lower doses increased the ovarian mass, number of Corpora lutea, number of harvested oocytes, zygotes and embryos at blastocyst stage derived from these zygotes after culture. These data demonstrate that dbcAMP can stimulate rabbit ovarian follicle atresia, ovulation, oocyte, zygote and embryo yield and development. Furthermore, they confirm in the involvement of cyclic nucleotide-dependent intracellular mechanisms in the control of rabbit reproductive functions and potential practical usefulness of dbcAMP in improving animal reproduction and fertility.

  11. Determining the protective function of sports footwear.

    Lake, M J

    2000-10-01

    To reduce the risk of injury associated with foot-ground interaction during sporting activities, there is a need for adequate assessment of the protective function of sports footwear. The present objectives are to review the typical biomechanical approaches used to identify protection offered by sports footwear during dynamic activities and to outline some of the recent methodological approaches aimed at improving this characterization. Attention is focused on biomechanical techniques that have been shown to best differentiate safety features of footwear. It was determined that subject tests would be used in combination with standard mechanical techniques to evaluate footwear protection. Impact attenuation characteristics of footwear during sporting activities were most distinguished by analysis of tibial shock signals in the frequency and joint time-frequency domains. It has been argued that lateral stability and traction properties of footwear are better assessed using game-like manoeuvres of subjects on the actual sporting surface. Furthermore, the ability of such tests to discriminate between shoes has been improved through methods aimed at reducing or accounting for variability in individual execution of dynamic manoeuvres. Advances in tools allowing measurement of dynamic foot function inside the shoe also aid our assessment of shoe protective performance. In combination, these newer approaches should provide more information for the design of safer sports footwear.

  12. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

    Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

    Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

  13. Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

    Anna Z. Szóstek

    2014-01-01

    Full Text Available The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL, IL-1β (10 ng/mL or IL-6 (10 ng/mL for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10−7 M; 17-β estradiol (E2; 10−9 M or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each for 24 h. The oxytocin (OT; 10−7 M was used as a positive control. In Experiment 3, cells were exposed to P4 (10−7 M, E2 (10−9 M or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy.

  14. Expression and Functional Pathway Analysis of Nuclear Receptor NR2F2 in Ovarian Cancer

    Hawkins, Shannon M.; Loomans, Holli A.; Wan, Ying-Wooi; Ghosh-Choudhury, Triparna; Coffey, Donna; Xiao, Weimin; Liu, Zhandong; Sangi-Haghpeykar, Haleh

    2013-01-01

    Context: Recent evidence implicates the orphan nuclear receptor, nuclear receptor subfamily 2, group F, member 2 (NR2F2; chicken ovalbumin upstream promoter-transcription factor II) as both a master regulator of angiogenesis and an oncogene in prostate and other human cancers. Objective: The objective of the study was to determine whether NR2F2 plays a role in ovarian cancer and dissect its potential mechanisms of action. Design, Setting, and Patients: We examined NR2F2 expression in healthy ovary and ovarian cancers using quantitative PCR and immunohistochemistry. NR2F2 expression was targeted in established ovarian cancer cell lines to assess the impact of dysregulated NR2F2 expression in the epithelial compartment of ovarian cancers. Results: Our results indicate that NR2F2 is robustly expressed in the stroma of healthy ovary with little or no expression in epithelia lining the ovarian surface, clefts, or crypts. This pattern of NR2F2 expression was markedly disrupted in ovarian cancers, in which decreased levels of stromal expression and ectopic epithelial expression were frequently observed. Ovarian cancers with the most disrupted patterns of NR2F2 were associated with significantly shorter disease-free interval by Kaplan-Meier analysis. Targeting NR2F2 expression in established ovarian cancer cell lines enhanced apoptosis and increased proliferation. In addition, we found that NR2F2 regulates the expression of NEK2, RAI14, and multiple other genes involved in the cell cycle, suggesting potential pathways by which dysregulated expression of NR2F2 impacts ovarian cancer. Conclusions: These results uncover novel roles for NR2F2 in ovarian cancer and point to a unique scenario in which a single nuclear receptor plays potentially distinct roles in the stromal and epithelial compartments of the same tissue. PMID:23690307

  15. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    Antonio Simone Laganà

    2016-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI and D-chiro-inositol (DCI, the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

  16. Functional role and prognostic significance of CD157 in ovarian carcinoma.

    Ortolan, Erika; Arisio, Riccardo; Morone, Simona; Bovino, Paola; Lo-Buono, Nicola; Nacci, Giulia; Parrotta, Rossella; Katsaros, Dionyssios; Rapa, Ida; Migliaretti, Giuseppe; Ferrero, Enza; Volante, Marco; Funaro, Ada

    2010-08-04

    CD157, an ADP-ribosyl cyclase-related cell surface molecule, regulates leukocyte diapedesis during inflammation. Because CD157 is expressed in mesothelial cells and diapedesis resembles tumor cell migration, we investigated the role of CD157 in ovarian carcinoma. We assayed surgically obtained ovarian cancer and mesothelial cells and both native and engineered ovarian cancer cell lines for CD157 expression using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and for adhesion to extracellular matrices, migration, and invasion using cell-based assays. We investigated invasion of human peritoneal mesothelial cells by serous ovarian cancer cells with a three-dimensional coculture model. Experiments were performed with or without CD157-blocking antibodies. CD157 expression in tissue sections from ovarian cancer patients (n = 88) was examined by immunohistochemistry, quantified by histological score (H score), and categorized as at or above or below the median value of 60, and compared with clinical parameters. Statistical tests were two-sided. CD157 was expressed by ovarian cancer cells and mesothelium, and it potentiated the adhesion, migration, and invasion of serous ovarian cancer cells through different extracellular matrices. CD157-transfected ovarian cancer cells migrated twice as much as CD157-negative control cells (P = .001). Blockage of CD157 inhibited mesothelial invasion by serous ovarian cancer cells in a three-dimensional model. CD157 was expressed in 82 (93%) of the 88 epithelial ovarian cancer tissue specimens. In serous ovarian cancer, patients with CD157 H scores of 60 or greater had statistically significantly shorter disease-free survival and overall survival than patients with lower CD157 H scores (CD157 H score > or =60 vs or =60 vs <60: median overall survival = 45 months, 95% CI = 21.21 to 68.79 vs unreached, P = .024). Multivariable Cox regression showed that CD157 is an independent prognostic factor for recurrence

  17. Ovarian hormones and obesity.

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  18. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

    Ahmet Ali Tuncer

    2016-01-01

    Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

  19. Radio-immunoassay of salivary progesterone for monitoring ovarian function in female infertility

    Luisi, M.; Franchi, F.; Bianchi, S.; Gravina, G.; Podesta, A.

    1987-01-01

    Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/I and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low-or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment

  20. Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients.

    Zhang, Jenny J; Wang, Molin

    2010-09-30

    Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing-hormone-releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen-receptor-positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease-free survival (DFS) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis.

  1. Radio-immunoassay of salivary progesterone for monitoring ovarian function in female infertility

    Luisi, M.; Franchi, F.; Bianchi, S.; Gravina, G.; Podesta, A.

    1987-01-01

    Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/I and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low-or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment.

  2. Role of the different sexuality domains on the sexual function of women with premature ovarian failure.

    Benetti-Pinto, Cristina Laguna; Soares, Patrícia Magda; Giraldo, Helena Patrícia Donovan; Yela, Daniela Angerame

    2015-03-01

    Women with premature ovarian failure (POF) often manifest complaints involving different aspects of sexual function (SF), regardless of using hormone therapy. SF involves a complex interaction between physical, psychological, and sociocultural aspects. There are doubts about the impact of different complaints on the global context of SF of women with POF. To evaluate the percentage of influence of each of the sexuality domains on the SF in women with POF. Cross-sectional study with 80 women with POF, matched by age to 80 women with normal gonadal function. We evaluated SF through the "Female Sexual Function Index" (FSFI), a comparison between the POF and control groups using the Mann-Whitney test. Component exploratory factor analysis was used to assess the proportional influence of each domain on the composition of the overall SF for women in the POF group. SF was evaluated using FSFI. Exploratory Factor Analysis for components was used to evaluate the role of each domain on the SF of women with POF. The FSFI score was significantly worse for women with POF, with a decrease in arousal, lubrication, orgasm, satisfaction, and dyspareunia. Exploratory factor analysis of SF showed that the domain with greater influence in the SF was arousal, followed by desire, together accounting for 41% of the FSFI. The domains with less influence were dyspareunia and lubrication, which together accounted for 25% of the FSFI. Women with POF have impaired SF, determined mainly by changes in arousal and desire. Aspects related to lubrication and dyspareunia complaints have lower determination coefficient in SF. These results are important in adapting the approach of sexual disorders in this group of women. © 2014 International Society for Sexual Medicine.

  3. GnRH-agonist implants suppress reproductive function and affects ovarian LHR and FSHR expression in prepubertal female cats.

    Mehl, N S; Srisuwatanasagul, S; Swangchan-Uthai, T; Sirivaidyapong, S; Khalid, M

    2017-01-01

    Effect of a GnRH-agonist (deslorelin) was studied on reproductive function and ovarian luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) expression in prepubertal female cats that were either implanted with 4.7-mg deslorelin (implanted: n = 6) or not (controls: n = 18) or ovariohysterectomized at prepubertal age (prepubertal OVH: n = 6). Body weights, fecal estradiol, and sexual behavior of implanted and control cats were monitored for 48 weeks followed by collection of ovaries and uteri. Ovaries and uteri were collected from control cats at follicular, luteal, and inactive stage (n = 6/group) and from prepubertal OVH cats at prepubertal age. Ovaries and uteri were analyzed for anatomical/histological characteristics. Ovaries were also analyzed for LHR and FSHR expression. Statistical analysis showed higher (P ≤ 0.05) body weight in control than implanted cats only during 22nd to 26th weeks of the study. Estrus was observed in control cats only. Deslorelin reduced (P ≤ 0.05) ovarian weight and number of antral follicles but did not affect endometrial thickness and gland diameter. However, myometrial thickness of implanted cats was significantly lower than control cats at follicular and luteal stage. Ovarian LHR mRNA expression was lower (P ≤ 0.05) in implanted cats than control cats at follicular stage. FSHR mRNA and LHR protein expression did not differ among the three groups. FSHR protein expression was lower (P ≤ 0.05) in prepubertal OVH cats and was not affected by deslorelin. In conclusion, deslorelin suppresses reproductive function in prepubertal female cats for at least 48 weeks possibly through a change in the ovarian mRNA expression of LHR. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  5. 3 to 5 Years Later: Long-term Effects of Prophylactic Bilateral Salpingectomy on Ovarian Function.

    Venturella, Roberta; Lico, Daniela; Borelli, Massimo; Imbrogno, Maria G; Cevenini, Gabriele; Zupi, Errico; Zullo, Fulvio; Morelli, Michele

    2017-01-01

    Preliminary data on the effects of prophylactic bilateral salpingectomy (PBS) show that postoperative ovarian function is preserved up to 3 months after surgery. The confirmation of PBS safety on ovarian function even many years after surgery is essential to reassure the medical community that this new strategy, recently proposed for the prevention of ovarian cancer, is at least able to avoid the risk of premature surgical menopause. We investigated whether the addition of PBS during total laparoscopic hysterectomy (TLH) causes long-term effects on ovarian function. An observational study (Canadian Task Force classification II-3). Department of Obstetrics and Gynecology, "Magna Graecia" University, Catanzaro, Italy. Seventy-nine patients who underwent TLH plus salpingectomy between September 2010 and September 2012 at our institution have been recalled to be submitted to ovarian reserve evaluation in February 2015. Eight of 79 women refused to participate in this follow-up study. The ovarian age of PBS patients has been determined through OvAge (OvAge sr., Catanzaro, Italy), a statistical model that combines antimüllerian hormone, follicle-stimulating hormone, 3-dimensional antral follicle count, vascular index, flow index, and vascular flow index values. The control group consisted of a large population of 652 healthy women (with intact uterus and adnexa) previously enrolled to build the OvAge model. Comparisons between ovarian ages of PBS patients and the control group have been assessed by analysis of covariance linear statistical modeling. The main outcome measurement was the differences in the behavior within OvAge/age relation between PBS and control women. Descriptive statistics of those 71 enrolled PBS patients are the following: age, 49.61 ± 2.15 years; OvAge, 49.22 ± 2.57 years; follicle-stimulating hormone, 43.02 ± 19.92 mU/mL; antimüllerian hormone, 0.12 ± 0.20 ng/mL; 3-dimensional antral follicle count, 1.91 ± 1.28; vascular index

  6. Recovery of ovarian function after postradiation menopause. Do FSH levels have a definitive prognostic value?

    Letur-Konirsch, H.; Guis, F.

    1996-01-01

    Menopause, conventionally defined as the permanent cessation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogeneic bone marrow transplantation for acute immuno-blastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular developments, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor. (author)

  7. Analysis of the relationship between temporary or permanent amenorrhea and ovarian function after uterine artery embolization

    Cao Manrui; He Jianlong; Liu Bingguang; Teng Yan; Sun Lihong

    2006-01-01

    Objective: To analyze the cases of amenorrhea after uterine artery embolization (UAE) and to find out the relationship with ovarian dysfunction or failure. Methods: Ten cases out of 287 patients with uterus myoma who underwent UAE were found amenorrhea. Six of them had temporary and 4 had permanent amenorrhea (38, 47, 48 and 48 years old). Preprocedural and postprocedural menstruations, blood FSH levels correlative factors including surgical operations, were observed and analyzed. Results: Menstruations of 6 cases with temporary amenorrhea were completely recovered without any significant changes in blood FSH levels, while 4 permanent amenorrhea cases demonstrated significant differences in blood FSH levels after the procedure. Their blood FSH were all > 20 u /L after UAE with one of them > 100 u /L 24 months later and another 38 year-old patient underwent surgical operation of ovaries bilaterally before UAE. Conclusions: Temporary amenorrhea may not mean ovarian dysfunction or failure. The probability of ovarian dysfunction or failure after UAE is low, which mainly occur in the peirmenopausal patients. Consideration of the probability of inducing early ovarian failure, caution should be taken for UAE on the patients having ovarian surgery before. (authors)

  8. Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers

    Dafou, Dimitra; Grun, Barbara; Sinclair, John

    2010-01-01

    lines. Using immunohistochemistry, 66% of 794 invasive ovarian tumors showed no EPB41L3 expression compared with only 24% of benign ovarian tumors and 0% of normal ovarian epithelial tissues. EPB41L3 was extensively methylated in ovarian cancer cell lines and primary ovarian tumors compared with normal...... (erythrocyte membrane protein band 4.1-like 3, alternative names DAL-1 and 4.1B) was a candidate ovarian cancer-suppressor gene. Immunoblot analysis showed that EPB41L3 was activated in TOV21G(+18) hybrids, expressed in normal ovarian epithelial cell lines, but was absent in 15 (78%) of 19 ovarian cancer cell...... tissues (P = .00004), suggesting this may be the mechanism of gene inactivation in ovarian cancers. Constitutive reexpression of EPB41L3 in a three-dimensional multicellular spheroid model of ovarian cancer caused significant growth suppression and induced apoptosis. Transmission and scanning electron...

  9. Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

    Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

    2017-01-01

    The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

  10. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  11. Autoimmune premature ovarian failure

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  12. Functional genetic polymorphisms and female reproductive disorders : Part I: polycystic ovary syndrome and ovarian response

    Simoni, M.; Tempfer, C. B.; Destenaves, B.; Fauser, B. C. J. M.

    2008-01-01

    BACKGROUND: The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome ( PCOS). Since an altered response to ovarian stimulation is

  13. Towards prevention of ovarian cancer.

    Ali, Aus Tariq

    2018-01-01

    Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Vocal parameters and voice-related quality of life in adult women with and without ovarian function.

    Ferraz, Pablo Rodrigo Rocha; Bertoldo, Simão Veras; Costa, Luanne Gabrielle Morais; Serra, Emmeliny Cristini Nogueira; Silva, Eduardo Magalhães; Brito, Luciane Maria Oliveira; Chein, Maria Bethânia da Costa

    2013-05-01

    To identify the perceptual and acoustic parameters of voice in adult women with and without ovarian function and its impact on quality of life related to voice. Cross-sectional and analytical study with 106 women divided into, two groups: G1, with ovarian function (n=43) and G2, without physiological ovarian function (n=63). The women were instructed to sustain the vowel "a" and the sounds of /s/ and /z/ in habitual pitch and loudness. They were also asked to classify their voices and answer the voice-related quality of life (V-RQOL) questionnaire. The perceptual analysis of the vocal samples was performed by three speech-language pathologists using the GRBASI (G: grade; R: roughness; B: breathness; A: asthenia; S: strain; I: instability) scale. The acoustic analysis was carried out with the software VoxMetria 2.7h (CTS Informatica). The data were analyzed using descriptive statistics. In the perceptual analysis, both groups showed a mild deviation for the parameters roughness, strain, and instability, but only G2 showed a mild impact for the overall degree of dysphonia. The mean of fundamental frequency was significantly lower for the G2, with a difference of 17.41Hz between the two groups. There was no impact on V-RQOL in any of the V-RQOL domains for this group. With the menopause, there is a change in women's voices, impacting on some voice parameters. However, there is no direct impact on their quality of life related to voice. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  15. Ovarian Disorders

    ... a pregnancy can occur. Ovaries also make the female hormones estrogen and progesterone. When a woman goes through menopause, her ovaries stop making those hormones and releasing eggs. Problems with the ovaries include Ovarian cancer Ovarian ...

  16. Function of hypothalamic-hypophyseal-ovarian system in radiation treatment of patients with cervical cancer

    Modnikov, O.P.

    1984-01-01

    Radioimmunoassay of the hypothalamic-hypophyseal-ovarian interrelationships was performed in 87 patients with cervical cancer and 37 practically healthy women. The basal level of the follicle-stimulating hormone (ESH), luteinizing hormone (LH) and estradiol as well as their response to the administration of the releasing factor of the hypothalamus (luliberin) were studied. Some disorders that manifested thermselved in the decreased level of estradiol, were established in the patients with cervical cancer even before irradiation. Concomitant radiation therapy resulted in pronounced changes in the activities of the hypothalamic-hypophyseal-ovarian system that manifested themselves in the lowered rate of LH increment in response to the administration of luliberin and the absence of estradiol response to the load. These changes persisted long after the termination of concomitant radiation therapy

  17. Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women.

    O'Donnell, Emma; Goodman, Jack M; Harvey, Paula J

    2011-12-01

    Evidence indicates that hypoestrogenemia is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovulatory disruption due to functional hypothalamic amenorrhea (FHA) are characterized by hypoestrogenemia. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Articles were found via PubMed search for both original and review articles based on peer review publications between 1974 and 2011 reporting on cardiovascular changes in women with FHA, with emphasis placed on women with EAA. Despite participation in regular exercise training, hypoestrogenic women with EAA demonstrate paradoxical changes in cardiovascular function, including endothelial dysfunction, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest that the beneficial effects of regular exercise training on vascular function are obviated in the face of hypoestrogenemia. The long-term cardiovascular consequences of altered vascular function in response to ovulatory disruption in women with EAA remain to be determined. Retrospective data, however, suggest premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovulatory disruption. Importantly, in women with EAA, estrogen therapy, folic acid supplementation without change in menstrual status, and resumption of menses restores endothelial function. In this review, we focus on the influence of hypoestrogenemia in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, lipid profile, and autonomic control of blood pressure, heart rate, and baroreflex sensitivity. The influence of exercise training is also considered. With the premenopausal years typically considered to be cardioprotective in association with normal ovarian function

  18. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-01-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) [follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml] and 17 β-estradiol (E 2 ) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E 2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E 2 , 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related

  19. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-01-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD [follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml] and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related

  20. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  1. Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

    Dumont, Agathe; Dewailly, Didier; Plouvier, Pauline; Catteau-Jonard, Sophie; Robin, Geoffroy

    2016-04-29

    Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called "FHA-PCOM", has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and "FHA-PCOM" patients in order to search for an eventual impact of PCOM. Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 "FHA-PCOM" patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with "FHA-PCOM". There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. Pulsatile GnRH seems to be a successful and safe method for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM.

  2. Ovarian volume throughout life

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

    2013-01-01

    conception to 82 years of age. This model shows that 69% of the variation in ovarian volume is due to age alone. We have shown that in the average case ovarian volume rises from 0.7 mL (95% CI 0.4-1.1 mL) at 2 years of age to a peak of 7.7 mL (95% CI 6.5-9.2 mL) at 20 years of age with a subsequent decline...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis......The measurement of ovarian volume has been shown to be a useful indirect indicator of the ovarian reserve in women of reproductive age, in the diagnosis and management of a number of disorders of puberty and adult reproductive function, and is under investigation as a screening tool for ovarian...

  3. Increasing age influences uterine integrity, but not ovarian function or oocyte quality, in the cheetah (Acinonyx jubatus).

    Crosier, Adrienne E; Comizzoli, Pierre; Baker, Tom; Davidson, Autumn; Munson, Linda; Howard, JoGayle; Marker, Laurie L; Wildt, David E

    2011-08-01

    Although the cheetah (Acinonyx jubatus) routinely lives for more than 12 yr in ex situ collections, females older than 8 yr reproduce infrequently. We tested the hypothesis that reproduction is compromised in older female cheetahs due to a combination of disrupted gonadal, oocyte, and uterine function/integrity. Specifically, we assessed 1) ovarian response to gonadotropins; 2) oocyte meiotic, fertilization, and developmental competence; and 3) uterine morphology in three age classes of cheetahs (young, 2-5 yr, n = 17; prime, 6-8 yr, n = 8; older, 9-15 yr, n = 9). Ovarian activity was stimulated with a combination of equine chorionic gonadotropin and human chorionic gonadotropin (hCG), and fecal samples were collected for 45 days before gonadotropin treatment and for 30 days after oocyte recovery by laparoscopy. Twenty-six to thirty hours post-hCG, uterine morphology was examined by ultrasound, ovarian follicular size determined by laparoscopy, and aspirated oocytes assessed for nuclear status or inseminated in vitro. Although no influence of age on fecal hormone concentrations or gross uterine morphology was found (P > 0.05), older females produced fewer (P 0.05) nuclear status and ability to reach metaphase II and fertilize in vitro. A histological assessment of voucher specimens revealed an age-related influence on uterine tissue integrity, with more than 87% and more than 56% of older females experiencing endometrial hyperplasia and severe pathologies, respectively. Our collective findings reveal that lower reproductive success in older cheetahs appears to be minimally influenced by ovarian and gamete aging and subsequent dysfunction. Rather, ovaries from older females are responsive to gonadotropins, produce normative estradiol/progestogen concentrations, and develop follicles containing oocytes with the capacity to mature and be fertilized. A more likely cause of reduced fertility may be the high prevalence of uterine endometrial hyperplasia and related

  4. BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation.

    Stordal, Britta

    2013-06-01

    Mutations in BRCA1\\/2 increase the risk of developing breast and ovarian cancer. Germline BRCA1\\/2 mutations occur in 8.6-13.7% of unselected epithelial ovarian cancers, somatic mutations are also frequent. BRCA1\\/2 mutated or dysfunctional cells may be sensitive to PARP inhibition by synthetic lethality. The aim of this study is to comprehensively characterise the BRCA1\\/2 status of a large panel of ovarian cancer cell lines available to the research community to assist in biomarker studies of novel drugs and in particular of PARP inhibitors. The BRCA1\\/2 genes were sequenced in 41 ovarian cell lines, mRNA expression of BRCA1\\/2 and gene methylation status of BRCA1 was also examined. The cytotoxicity of PARP inhibitors olaparib and veliparib was examined in 20 cell lines. The cell line SNU-251 has a deleterious BRCA1 mutation at 5564G > A, and is the only deleterious BRCA1\\/2 mutant in the panel. Two cell lines (UPN-251 and PEO1) had deleterious mutations as well as additional reversion mutations that restored the protein functionality. Heterozygous mutations in BRCA1\\/2 were relatively common, found in 14.6% of cell lines. BRCA1 was methylated in two cell lines (OVCAR8, A1847) and there was a corresponding decrease in gene expression. The BRCA1 methylated cell lines were more sensitive to PARP inhibition than wild-type cells. The SNU-251 deleterious mutant was more sensitive to PARP inhibition, but only in a long-term exposure to correct for its slow growth rate. Cell lines derived from metastatic disease are significantly more resistant to veliparib (2.0 fold p = 0.03) compared to those derived from primary tumours. Resistance to olaparib and veliparib was correlated Pearsons-R 0.5393, p = 0.0311. The incidence of BRCA1\\/2 deleterious mutations 1\\/41 cell lines derived from 33 different patients (3.0%) is much lower than the population incidence. The reversion mutations and high frequency of heterozygous mutations suggest that there is a selective

  5. Functionality of Ventilated Facades: Protection of Insulation

    Petrichenko Mikhail

    2016-01-01

    Full Text Available This article discusses about methods of construction of the ventilated facades. The ventilated facade is not only the element of facing, it is the supporting structure. Their main objective - creation of air ventilating space between a facade and an external wall of the building. Moving of air in this gap protects a heater from destruction, interfering with a moisture congestion. In addition, the ventilated facade protect the building from aggressive influence of external environment, have a sound and thermal insulation properties. There are several problems of systems of the ventilated facades connected with an application of a heater. For more effective using it is necessary to minimize contact of a heater with environment.

  6. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer.

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V; Bean, Yukie; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Anne; Chen, Zhihua; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T; Edwards, Robert P; Eilber, Ursula; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; James, Paul; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kruger Kjaer, Susanne; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph L; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Nevanlinna, Heli; McNeish, Ian; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Sellers, Thomas A; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston, Lara; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Monteiro, Alvaro; Pharoah, Paul D; Gayther, Simon A; Freedman, Matthew L

    2015-09-22

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

  7. Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes.

    Wong, M; O'Neill, S; Walsh, G; Smith, I E

    2013-01-01

    Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex®), used with chemotherapy to preserve ovarian function and maintain fertility. Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses. About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n=30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries. The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.

  8. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

  9. Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols

    Alviggi, Carlo; Humaidan, Peter; Ezcurra, Diego

    2012-01-01

    single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical...... practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully...

  10. The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated

    Shahab Shubin W

    2012-08-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs. Methods In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128. We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested. Results While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication. Conclusions The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.

  11. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity

    Bhattacharya, Poulomi; Keating, Aileen F., E-mail: akeating@iastate.edu

    2012-06-15

    The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants. -- Highlights: ► Summary of ovotoxicant action during ovotoxicity. ► Discussion of impact of biotransformation on chemical toxicity. ► Identification of knowledge gaps in chemical metabolism.

  12. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity

    Bhattacharya, Poulomi; Keating, Aileen F.

    2012-01-01

    The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants. -- Highlights: ► Summary of ovotoxicant action during ovotoxicity. ► Discussion of impact of biotransformation on chemical toxicity. ► Identification of knowledge gaps in chemical metabolism.

  13. Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

    Bhattacharya, Poulomi, E-mail: poulomib@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2012-04-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression. -- Highlights: ► Ovarian GSTP is activated in response to DMBA exposure. ► AhR and Nrf2 transcription factors are up-regulated by DMBA. ► PI3K signaling regulates Ahr, Nrf2 and Gstp expression. ► GSTP negatively regulates ovarian JNK in response to DMBA exposure.

  14. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    Shamberger, R.C. (National Inst. of Health, Bethesda, MD); Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  15. [DONG's extraordinary acupoints for the ovarian function of polycystic ovary syndrome:a randomized controlled pilot trial].

    Cao, Yu; Zhang, Li; Zhao, Danyang; Liu, Zhishun

    2017-07-12

    To preliminary assess the efficacy of DONG 's extraordinary acupoints for the ovarian function of polycystic ovary syndrome. Fifty-six patients were randomized into an acupuncture group and a western medication group. In the acupuncture group, the acupoints were Fuke, Huanchao, Tianhuang (Yinlingquan, SP 9), Renhuang (Sanyinjiao, SP 6), Guanyuan (CV 4), Zigong (EX-CA 1). The treatment was used twice a week for continuous 12 weeks. In the western medication group, patients were given diane-35 for 3 menstrual cycles, once a day for 21 days with 7 days between the two sessions. The ratio of luteinizing hormone/flitropin (LH/FSH) was taken as the primary index, while the secondary indices were serum testosterone (T), FSH, LH, body mass index (BMI), the condition of ovary and menstruation. ①After treatment, the ratio of LH/FSH declined in both the two groups ( P 0.05). ②T, LH and BMI dropped in the two groups ( P 0.05). ③The size of ovary did not change significantly after treatment in the two groups (both P >0.05), but the reduction degree of ovary size of the acupuncture group was larger than that of the western medication group ( P ovary number of more than 10 foliiculi in single ovary in the acupuncture group reduced compared with that before treatment ( P ovary number with the above feature was not significantly different between the two groups ( P >0.05). ④The times and days of menstruation within 3 months increased significantly in the two groups (all P 0.05). DONG 's extraordinary acupoints could improve the ovarian function of polycystic ovary syndrome, whose effect is similar as diane-35.

  16. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model.

    Dongmei Lai

    Full Text Available Skin-derived mesenchymal stem cells (SMSCs can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs and male skin-derived mesenchymal stem cells (M-SMSCs from red fluorescence protein (RFP transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

  17. Anti-Mullerian hormone and ovarian dysfunction

    Broekmans, Frank J.; Visser, Jenny A.; Laven, Joop S. E.; Broer, Simone L.; Themmen, Axel P. N.; Fauser, Bart C.

    2008-01-01

    Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are

  18. Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

    Qing Li

    Full Text Available Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I; cyclophosphamide only (group II; cyclophosphamide plus GnRHa (group III; cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV. Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

  19. Acupuncture Mechanisms: Anesthesia, Analgesia and Protection on Organ Functions

    Jing Wang

    2015-01-01

    Full Text Available Acupuncture, as a healing art in traditional Chinese medicine, has been widely used to treat various diseases. In the history of acupuncture anesthesia, in the past decades, mechanisms of acupuncture analgesia has been widely investigated, and in recent years, acupuncture protection on organ functions has attracted great interest. This review summarized the research progress on mechanisms of acupuncture for analgesia and its protection against organ function injury in anesthesia, and its perspective of analgesia, immunomodulation, neuroendocrine regulation and multiple organ protection. The current evidence supports that acupuncture analgesia and its organ protection in anesthesia is associated with the integration of neuroendocrine-immune networks in the level of neurotransmitters, cytokines, hormones, neuronal ensembles, lymphocytes, and endocrine cells. Although the mechanisms of acupuncture analgesia and its organ protection are still not completely understood, basic as well as clinic researches on the mechanisms and applications of acupuncture and related techniques are being carried out.

  20. Protective effects of tempol in an experimental ovarian ischemia-reperfusion injury model in female Wistar albino rats.

    Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi

    2017-07-01

    The aim of this study was to investigate the antioxidant effects of tempol on ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I); Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50 mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia group and the I/R group than in the sham group. Catalase levels were significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30 mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group. The levels of the histopathological parameters were significantly decreased in the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be used for reducing ovarian I/R injury.

  1. Ovarian transposition in young women and fertility sparing.

    Mossa, B; Schimberni, M; Di Benedetto, L; Mossa, S

    2015-09-01

    Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

  2. Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

    L. Armada-Dias

    2001-09-01

    Full Text Available The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10, hypothyroid (N = 10, treated with 0.05% 6-propyl-2-thiouracil (PTU in drinking water for 60 days, and T4-treated group (N = 10, receiving daily sc injections of L-thyroxine (0.8 µg/100 g body weight during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

  3. Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

    Armada-Dias L.

    2001-01-01

    Full Text Available The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10, hypothyroid (N = 10, treated with 0.05% 6-propyl-2-thiouracil (PTU in drinking water for 60 days, and T4-treated group (N = 10, receiving daily sc injections of L-thyroxine (0.8 µg/100 g body weight during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

  4. Growth and ovarian function in girls with 48,XXXX karyotype--patient report and review of the literature.

    Rooman, Raoul P A; Van Driessche, Karen; Du Caju, Marc V L

    2002-01-01

    The loss of an X chromosome results in short stature and often in primary ovarian failure, but the effect of extra X chromosomes is less clear, especially in 48,XXXX women. We report a girl with a 48,XXXX karyotype with tall stature (181.8 cm), primary ovarian failure and low DHEAS levels. A review of the literature shows that, apart from an intellectual deficit, the phenotype is very heterogeneous. The few data that are available in the literature indicate that tall stature and primary ovarian failure are not essential characteristics of the 48,XXXX phenotype.

  5. Ovarian lymphoma

    Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

    2012-01-01

    50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

  6. Ovarian cancer

    ... injected directly into the abdominal cavity (intraperitoneal, or IP). Radiation therapy is rarely used to treat ovarian ... About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright ...

  7. Ovarian Cancer

    ... I find more information about ovarian and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  8. Influence of ovarian manipulation on reproductive endocrinology in polycystic ovarian syndrome and regularly cycling women

    Hendriks, M.L.; König, T.E.; Soleman, R.S.; Korsen, T.; Schats, R.; Hompes, P.G.A.; Homburg, R.R.; Lambalk, C.B.

    2013-01-01

    Objective: Little is known about the function of the ovarian neuronal network in humans. In many species, copulation influences endocrinology through this network. As a first step, the possible influence of ovarian mechanical manipulation on pituitary and ovarian hormones was evaluated in polycystic

  9. Primary ovarian insufficiency: an update

    Cox L

    2014-02-01

    Full Text Available Leticia Cox, James H LiuUH Case Medical Center, MacDonald Women's Hospital, Department of Obstetrics and Gynecology, Case Western Reserve University School of Medicine, Department of Reproductive Biology, Cleveland, OH, USAAbstract: Primary ovarian insufficiency is a condition that represents impaired ovarian function on a continuum with intermittent ovulation. This condition commonly leads to premature menopause, defined as cessation of ovulation prior to the age of 40 years. Because there are potential immediate and long-term consequences of hypoestrogenism, a timely diagnosis is invaluable. This comprehensive review will discuss identifiable causes for primary ovarian insufficiency, including genetic disorders and metabolic abnormalities, as well as review current strategies for diagnosis, evaluation, and management of women with this condition.Keywords: premature ovarian failure, premature menopause, ovarian dysfunction

  10. Multiple roles of hypoxia in ovarian function: roles of hypoxia-inducible factor-related and -unrelated signals during the luteal phase

    Nishimura, Ryo; Okuda, Kiyoshi

    2015-01-01

    There is increasing interest in the role of oxygen conditions in the microenvironment of organs because of the discovery of a hypoxia-specific transcription factor, namely hypoxia-inducible factor (HIF) 1. Ovarian function has several phases that change day by day, including ovulation, follicular growth and corpus luteum formation and regression. These phases are regulated by many factors, including pituitary hormones and local hormones, such as steroids, peptides and cytokines, as well as ox...

  11. The role of mTOR in ovarian cancer, polycystic ovary syndrome and ovarian aging.

    Liu, Jin; Wu, Dai-Chao; Qu, Li-Hua; Liao, Hong-Qing; Li, Mei-Xiang

    2018-05-12

    The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  12. Normal left ventricular function does not protect against propafenone ...

    Normal left ventricular function does not protect against propafenone-induced incessant ventricular tachycardia. R. N. Scott Millar, J. B. Lawrenson, D.A. Milne. Abstract. Propafenone is a class Ic anti-arrhythmic agent with mild B-blocking properties which has recently become available in South Africa. We have used the ...

  13. Ovarian function in survivors of childhood medulloblastoma: Impact of reduced dose craniospinal irradiation and high-dose chemotherapy with autologous stem cell rescue.

    Balachandar, Sadana; Dunkel, Ira J; Khakoo, Yasmin; Wolden, Suzanne; Allen, Jeffrey; Sklar, Charles A

    2015-02-01

    Data on ovarian function (OvF) in medulloblastoma (MB) survivors is limited, with most studies describing outcomes in survivors treated with craniospinal irradiation (CSI) doses >24 Gy ± standard chemotherapy. The objective of the current study is to report on OvF: (i) across a range of CSI doses; and (ii) following high-dose chemotherapy with autologous stem cell rescue (ASCR). Retrospective review of female MB survivors who were diagnosed in childhood and followed at Memorial Sloan Kettering Cancer Center. Patients were divided into three groups: (i) CSI ≤24 Gy +/- standard chemotherapy; (ii) CSI ≥35 Gy +/- standard chemotherapy; and (iii) high-dose chemotherapy with ASCR +/- CSI. Primary ovarian dysfunction (POD) occurred in 2/17 subjects in group 1, 3/9 subjects in group 2 and 5/5 subjects in group 3 (P < 0.01). Normalization of function was noted in four subjects with POD. Persistent POD requiring hormone replacement (POF) was observed in 1/17 subjects in group 1, 2/9 in group 2, and 3/5 in group 3 (P = 0.02). Neither age at treatment nor type of standard chemotherapy correlated with risk of POD or POF. Both POD and POF appear to occur in a small proportion of patients who are treated with contemporary doses of CSI +/- standard chemotherapy. However, ovarian dysfunction requiring hormone replacement therapy is common following high-dose chemotherapy associated with ASCR. These findings will assist clinicians in counseling patients regarding fertility preservation and risk of impaired ovarian function/future fertility. Pediatr Blood Cancer 2015;62:317-321. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  14. Overexpression of miR-21 in stem cells improves ovarian structure and function in rats with chemotherapy-induced ovarian damage by targeting PDCD4 and PTEN to inhibit granulosa cell apoptosis.

    Fu, Xiafei; He, Yuanli; Wang, Xuefeng; Peng, Dongxian; Chen, Xiaoying; Li, Xinran; Wang, Qing

    2017-08-14

    Chemotherapy-induced premature ovarian failure (POF) is a severe complication affecting tumor patients at a childbearing age. Mesenchymal stem cells (MSCs) can partially restore the ovarian structure and function damaged by chemotherapy. miR-21 is a microRNA that can regulate cell apoptosis. This study discusses the repair effect and mechanism of MSCs overexpressing miR-21 on chemotherapy-induced POF. Rat MSCs and granulosa cells (GCs) were isolated in vitro. MSCs were transfected with miR-21 lentiviral vector (LV-miR-21) to obtain MSCs stably expressing miR-21 (miR-21-MSCs). The microenvironment of an ovary receiving chemotherapy was mimicked by adding phosphamide mustard (PM) into the cellular culture medium. The apoptosis rate and the mRNA and protein expression of target genes PTEN and PDCD4 were detected in MSCs. Apoptosis was induced by adding PM into the culture medium for GCs, which were cocultured with miR-21-MSCs. The apoptosis rate and the mRNA and protein expression of PTEN and PDCD4 were detected. The chemotherapy-induced POF model was built into rats by intraperitoneal cyclophosphamide injection. miR-21-MSCs were transplanted into the bilateral ovary. The rats were sacrificed at 15, 30, 45, and 60 days after the last injection. The ovarian weights, follicle count, estrous cycle, and sex hormone levels (estradiol (E2) and follicle-stimulating hormone (FSH)) were detected. Apoptosis of GCs was determined by TUNEL assay. The miR-21 and mRNA and protein expression of PTEN and PDCD4 were determined. The apoptosis decreased in MSCs transfected with miR-21. The mRNA and protein expression of target genes PTEN and PDCD4 was downregulated. GCs cocultured with miR-21-MSCs showed a decreased apoptosis, an upregulation of miR-21, and a downregulation of PTEN and PDCD4. Following the injection of miR-21-MSCs, the ovarian weight and follicle counts increased; E 2 levels increased while FSH levels decreased, with less severe apoptosis of GCs. The miR-21 expression

  15. Acute onset of ovarian dysfunction in young females after start of cancer treatment

    Mörse, Helena; Elfving, Maria; Lindgren, Anna

    2013-01-01

    Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors.......Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors....

  16. Analysis of the functional state of students in the process of healthy training exercises in different phases of the ovarian-menstrual cycle

    N.V. Petrenko

    2017-11-01

    Full Text Available Aim: to substantiate the application of a rational program of health-training sessions in the educational process of physical education of students in different phases of the ovarian-menstrual cycle. Material: in study participated students (n=127, who did not have deviations in health (the main medical group. According to the results of the tests were determined: heart rate; blood pressure; vital capacity of the lungs. To determine physical performance was used Harvard step-test. Physical exercises from the main means of health fitness were used differentially and dosed. Results: It was established that the consideration in the phases of the ovarian-menstrual cycle of indicators of the functional state, changes in well-being and working capacity give an opportunity: planning loads in the training process; adjustment of volume and intensity of loads. We recommend to schedule the load of our program as follows: in the menstrual phase - the development of flexibility (moderate load; in the postmenstrual phase - development of coordination, overall endurance; in ovulatory - speed development; in postovulatory - development of special endurance; in premenstrual - the development of strength, flexibility. In the postmenstrual and postovulatory phase, a high level of physical working capacity, functional state of the cardiopulmonary system has been registered. It also has a positive effect on body weight correction in the women students. Conclusions: When developing programs of health training sessions with women students it is necessary to take into account the phases of the ovarian-menstrual cycle.

  17. ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats.

    Zheng, Qin; Li, Yulin; Zhang, Dandan; Cui, Xinyuan; Dai, Kuixing; Yang, Yu; Liu, Shuai; Tan, Jichun; Yan, Qiu

    2017-10-26

    Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by polycystic ovaries, hyperandrogenism and anovulation. It is one of the main causes of infertility. RU486 is an antagonist of progesterone receptor, and most commonly used as a contraceptive. However, whether RU486 is correlated with PCOS remains unclear. Atrial natriuretic peptide (ANP) is a small peptide with natriuretic and diuretic functions, and its availability to be used in PCOS treatment is unknown. Here, we showed that the serum ANP level was lower in PCOS patients than that in healthy women, and it was also decreased in the serum and ovarian tissues of RU486-induced PCOS rats compared with the control rats. We also found that RU486 inhibited the proliferation and promoted the apoptosis of human KGN ovarian granulosa cells by downregulating progesterone receptor membrane component 1 (PGRMC1). Meantime, ANP promoted the proliferation and inhibited the apoptosis of KGN cells through upregulating ANP receptor A (NPRA). The promotive effects of ANP on ovarian functions were mediated through the formation of an NPRA/PGRMC1/EGFR complex, which further activated MAPK/ERK signaling and transcription factor AP1. Moreover, ANP treatment reversed the PCOS symptoms, and improved the fertility of RU486-induced PCOS rats. Collectively, these findings highlight that RU486 is associated with the pathogenesis of PCOS, and ANP treatment may be a promising therapeutic option for PCOS.

  18. No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

    Demeestere, Isabelle; Brice, Pauline; Peccatori, Fedro A; Kentos, Alain; Dupuis, Jehan; Zachee, Pierre; Casasnovas, Olivier; Van Den Neste, Eric; Dechene, Julie; De Maertelaer, Viviane; Bron, Dominique; Englert, Yvon

    2016-08-01

    We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma. © 2016 by American Society of Clinical Oncology.

  19. Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer.

    Lu, Lingeng; Katsaros, Dionyssios; Mayne, Susan T; Risch, Harvey A; Benedetto, Chiara; Canuto, Emilie Marion; Yu, Herbert

    2012-11-01

    Several single-nucleotide polymorphisms (SNPs) of the stem cell-associated gene lin-28B have been identified in association with ovarian cancer and ovarian cancer-related risk factors. However, whether these SNPs are functional or might be potential biomarkers for ovarian cancer prognosis remains unknown. The purposes of this study were to investigate the functional relevance of the identified lin-28B SNPs, as well as the associations of genotype and phenotype with epithelial ovarian cancer (EOC) survival. We analyzed five SNPs and mRNA levels of lin-28B in 211 primary EOC tissues using Taqman(®) SNP genotyping assays and SYBR green-based real-time PCR, respectively. The RNA secondary structures at the region of a genome-wide association-identified intronic rs314276 were analyzed theoretically with mfold and experimentally with circular dichroism spectroscopy. We found that rs314276 was a cis-acting expression quantitative trait locus (eQTL) in both additive and dominant models, while rs7759938 and rs314277 were significant or of borderline significance in dominant models only. The rs314276 variant significantly affects RNA secondary structure. No SNPs alone were associated with patient survival. However, we found that among patients initially responding to chemotherapy, those with higher lin-28B expression had higher mortality risk (hazard ratio =3.27, 95% confidence interval: 1.63-6.56) and relapse risk (hazard ratio = 2.53, 95% confidence interval: 1.41-4.54) than those with lower expression, and these associations remained in multivariate analyses. These results suggest that rs314276 alters RNA secondary structure and thereby influences gene expression, and that lin-28B is a cancer stem cell-associated marker, which may be a pharmaceutical target in the management of EOC.

  20. Development of Functional Foods for Body Protection Using Radiation

    Jo, S. K.; Jung, U. H.; Park, H. R.

    2007-07-15

    We have previously developed two herbal compositions(HemoHIM, HemoTonic) that protects immune/hematopoietic system and self-renewal tissues against radiation and enhances immune/hematopoietic functions. In this study, we tried to expand its usability by verifying its protective activity against various harmful stimuli as well as radiation. HemoHIM was shown to be highly effective in reducing immune/hematopoietic damage, particularly, normalizing the Th1/Th2 imbalance, which seemed to be a result of increased production of IL-12p70 by APC and enhanced NK cell activity. Also HemoHIM was shown to have protective activities against UV-induced skin damage, immune system damage by an anticancer drug (CP), immune depression by old age and stress, and inflammation. Finally it was confirmed in a human study that HemoHIM improves the immune cell functions and cytokine production. Based on these results, HemoHIM has been approved as a health functional food for immunomodulation by Korea FDA and succeeded in its industrialization. Meanwhile, to develop functional foods for the reduction of chronic radiation damage (carcinogenesis), we have screened natural products for inhibitory activities against carcinogenesis-related factors, and developed two anti-carcinogenic compositions. Also 6 single compounds were isolated and identified from radioprotective natural products and elucidated some synergistic protection by several single compounds and established a basis for the development of advanced technology for radioprotection. Also, to obtain the applicability of radiation technology for the safe sanitatation and distribution of functional food materials, we verified the toxicological safety, stability of activity and active components of irradiated medicinal herbs

  1. Development of Functional Foods for Body Protection Using Radiation

    Jo, S. K.; Jung, U. H.; Park, H. R.

    2007-07-01

    We have previously developed two herbal compositions(HemoHIM, HemoTonic) that protects immune/hematopoietic system and self-renewal tissues against radiation and enhances immune/hematopoietic functions. In this study, we tried to expand its usability by verifying its protective activity against various harmful stimuli as well as radiation. HemoHIM was shown to be highly effective in reducing immune/hematopoietic damage, particularly, normalizing the Th1/Th2 imbalance, which seemed to be a result of increased production of IL-12p70 by APC and enhanced NK cell activity. Also HemoHIM was shown to have protective activities against UV-induced skin damage, immune system damage by an anticancer drug (CP), immune depression by old age and stress, and inflammation. Finally it was confirmed in a human study that HemoHIM improves the immune cell functions and cytokine production. Based on these results, HemoHIM has been approved as a health functional food for immunomodulation by Korea FDA and succeeded in its industrialization. Meanwhile, to develop functional foods for the reduction of chronic radiation damage (carcinogenesis), we have screened natural products for inhibitory activities against carcinogenesis-related factors, and developed two anti-carcinogenic compositions. Also 6 single compounds were isolated and identified from radioprotective natural products and elucidated some synergistic protection by several single compounds and established a basis for the development of advanced technology for radioprotection. Also, to obtain the applicability of radiation technology for the safe sanitatation and distribution of functional food materials, we verified the toxicological safety, stability of activity and active components of irradiated medicinal herbs

  2. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... sampling. We required that cases and controls have no previous cancer and that controls have no previous bilateral oophorectomy. METHODS: Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders. MAIN OUTCOME MEASURES: Epithelial...

  3. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility — A Review

    Fernanda Cavallari de Castro

    2016-08-01

    Full Text Available Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9 and the bone morphogenetic protein 15 (BMP15, belong to the transforming growth factor beta (TGF-β superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR. These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

  4. Computer Forensic Function Testing: Media Preparation, Write Protection And Verification

    Yinghua (David Guo

    2010-06-01

    Full Text Available Normal 0 false false false EN-US JA AR-SA The growth in the computer forensic field has created a demand for new software (or increased functionality to existing software and a means to verify that this software is truly forensic i.e. capable of meeting the requirements of the trier of fact. In this work, we review our previous work---a function oriented testing framework for validation and verification of computer forensic tools. This framework consists of three parts: function mapping, requirements specification and reference set development. Through function mapping, we give a scientific and systemical description of the fundamentals of computer forensic discipline, i.e. what functions are needed in the computer forensic investigation process. We focus this paper on the functions of media preparation, write protection and verification. Specifically, we complete the function mapping of these functions and specify their requirements. Based on this work, future work can be conducted to develop corresponding reference sets to test any tools that possess these functions.

  5. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER......'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk....

  6. Effects of breed and feeding system on milk production, body weight, body condition score, reproductive performance, and postpartum ovarian function.

    Walsh, S; Buckley, F; Pierce, K; Byrne, N; Patton, J; Dillon, P

    2008-11-01

    The objective of this study was to investigate the potential differences among Holstein-Friesian (HF), Montbéliarde (MB), Normande (NM), Norwegian Red (NRF), Montbéliarde x Holstein-Friesian (MBX), and Normande x Holstein-Friesian (NMX) across 2 seasonal grass-based systems of milk production. The effects of breed and feeding system on milk production, body weight, body condition score, fertility performance, hormone parameters, ovarian function, and survival were determined by using mixed model methodology, generalized linear models, and survival analysis. The 5-yr study comprised up to 749 lactations on 309 cows in one research herd. The HF produced the greatest yield of solids-corrected milk, the MB and NM produced the least yields, and NRF, MBX, and NMX were intermediate. The NRF had the lowest body weight throughout lactation, the NM had the highest, and the other breeds were intermediate. Body condition score was greatest for MB and NM, least for HF, and intermediate for NRF, MBX, and NMX. The HF had a lower submission rate and overall pregnancy rate compared with the NRF. The NRF survived the longest in the herd, the HF survived the shortest, and the NM, MB, MBX, and NMX were intermediate. Breed of dairy cow had no effect on selected milk progesterone parameters from 5 d postpartum until 26 d after first artificial insemination. Breed of dairy cow did not influence insulin and insulin-like growth factor-1 around parturition or at the start of the breeding season. Animals offered a high-concentrate diet had greater milk yield, but they did not have improved reproductive performance. Differences observed between the different breeds in this study are a likely consequence of the past selection criteria for the respective breeds.

  7. Secretory function of ovarian cells and myometrial contractions in cow are affected by chlorinated insecticides (chlordane, heptachlor, mirex) in vitro

    Wrobel, Michael Hubert; Mlynarczuk, Jaroslaw

    2017-01-01

    The aim of the study was to investigate the effect of chlordane, heptachlor and mirex, on hormonal regulation of the force of myometrial contractions. Myometrial, endometrial, granulosa and luteal cells as well as strips of myometrium from non-pregnant cows were incubated with three insecticides at environmentally relevant doses (0.1, 1 or 10 ng/ml). None of the insecticides affected the viability of studied cells. Chlordane stimulated, while heptachlor and mirex inhibited, secretion of testosterone and estradiol from granulosa cells as well as secretion of progesterone from luteal cells, respectively. Secretion of oxytocin (OT) from granulosa cells was increased after incubation with all studied insecticides. Only mirex stimulated OT secretion from luteal cells, while heptachlor inhibited this effect. None of them affected synthesis of OT in luteal cells and prostaglandins (PGF2 and PGE2) secretion from uterine cells, except PGE2 secretion from endometrial cells was decreased when the cells were incubated with 0.1 ng/ml of chlordane. Basal and OT-stimulated myometrial contractions were increased by mirex and decreased by heptachlor. The data show that the insecticides altered secretory function of ovarian cells. Heptachlor and mirex affected also myometrial contractions in vitro, but uterine secretion of prostaglandins were not involved in the mechanism of that adverse effect of insecticides. The data indicate on potential of these insecticides to disturb fertilisation, blastocyst implantation or even the length of gestation. - Highlights: • The studied insecticides affected steroids and oxytocin secretion from ovaries. • Mirex stimulated bovine myometrial contractions. • Heptachlor inhibited bovine myometrial contractions. • Prostaglandins are not involved in adverse effect of the insecticides on uterine contractions.

  8. Standards for the Protection of Skin Barrier Function.

    Giménez-Arnau, Ana

    2016-01-01

    The skin is a vital organ, and through our skin we are in close contact with the entire environment. If we lose our skin we lose our life. The barrier function of the skin is mainly driven by the sophisticated epidermis in close relationship with the dermis. The epidermal epithelium is a mechanically, chemically, biologically and immunologically active barrier submitted to continuous turnover. The barrier function of the skin needs to be protected and restored. Its own physiology allows its recovery, but many times this is not sufficient. This chapter is focused on the standards to restore, treat and prevent barrier function disruption. These standards were developed from a scientific, academic and clinical point of view. There is a lack of standardized administrative recommendations. Still, there is a walk to do that will help to reduce the social and economic burden of diseases characterized by an abnormal skin barrier function. © 2016 S. Karger AG, Basel.

  9. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases

    Bukovský, Antonín

    2015-01-01

    Roč. 13, Feb 25 (2015), č. článku 10. ISSN 1477-7827 Institutional support: RVO:86652036 Keywords : In vitro maturation * in vitro fertilization * ovarian stem cells Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.147, year: 2015

  10. Clinicoroentgenological diagnosis of chronic venous ovarian insufficiency

    Grakova, L.S.; Galkin, E.V.; Naumova, E.B.

    1989-01-01

    The paper is devoted to clinicoroentgenological correlations of venous renogonadal hemodynamics in 168 women of reproductive age (151 women with infertility, habitual abortion, disordered menstrual function and 17 patients without disorders of the reproductive tract). Clinicolaboratory investigation was followed by visceral and parietal flebography for the detection of a pathological venous reflux into the ovarian pampiniform plexus. Clinicoroentgenological semiotics of chronic venous ovarian insufficiency was analyzed. Infertility was shown to be the main clinical manifestation of ovarian varicocele

  11. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    Ramaseshan, Ramakrishnan; Sundarrajan, Subramanian; Liu, Yingjun; Barhate, R S; Lala, Neeta L; Ramakrishna, S

    2006-01-01

    A catalyst for the detoxification of nerve agents is synthesized from β-cyclodextrin (β-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with β-CD, IBA, a blend of β-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane

  12. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    Ramaseshan, Ramakrishnan; Sundarrajan, Subramanian; Liu, Yingjun; Barhate, R. S.; Lala, Neeta L.; Ramakrishna, S.

    2006-06-01

    A catalyst for the detoxification of nerve agents is synthesized from β-cyclodextrin (β-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with β-CD, IBA, a blend of β-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane.

  13. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    Ramaseshan, Ramakrishnan [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Sundarrajan, Subramanian [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Liu, Yingjun [Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore (Singapore); Barhate, R S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Lala, Neeta L [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Ramakrishna, S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore)

    2006-06-28

    A catalyst for the detoxification of nerve agents is synthesized from {beta}-cyclodextrin ({beta}-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with {beta}-CD, IBA, a blend of {beta}-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane.

  14. Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

    Carmina, Enrico; Fruzzetti, Franca; Lobo, Roger A

    2016-06-01

    Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also

  15. Effects of progestagens and prostaglandin analogues on ovarian function and embryo viability in sheep.

    Gonzalez-Bulnes, A; Veiga-Lopez, A; Garcia, P; Garcia-Garcia, R M; Ariznavarreta, C; Sanchez, M A; Tresguerres, J A F; Cocero, M J; Flores, J M

    2005-06-01

    Current study assessed differences in the response of sheep to estrus synchronization either by the administration of two doses of prostaglandin or by the insertion of an intravaginal progestagen sponge. The preovulatory follicular dynamics and estradiol secretion, the ovulatory response and progesterone secretion and the number and quality of embryos were studied in 27 ewes treated with two doses of 100 microg of cloprostenol, 10 days apart, and in 29 sheep treated with progestagen sponges for 14 days. Percentage of sheep responding to the synchronization treatments with signs of estrus behaviour was similar between both groups (81.5% versus 72.4%, respectively). The use of progestagen resulted in a higher diameter of the largest follicle (6.6+/-0.2 versus 5.9+/-0.2, Psheep (Pprogesterone concentration during the early luteal phase was again higher in sheep treated with cloprostenol (P<0.05). The mean number of retrieved oocytes/embryos was very similar in both treatments (1.2+/-0.2 versus 1.4+/-0.2) and showed similar fertilization rates (70.6% versus 66.7%), but, although differences did not reach statistical significance, final viability rate was higher in cloprostenol than in progestagen treated ewes (58.9% versus 46.1%, P=0.07). Current results give new evidences supporting the negative effects of progestagens on the functionality of ovulatory follicles and support the development of new protocols for assisted reproduction including the use of prostaglandin analogues.

  16. Role of serylamino as a protector against gamma rays hazards on ovarian functions, carbohydrate and lipid metabolism during meta-estrous stage in rats

    Abou-Safi, KM.

    2005-01-01

    In this study, functional investigations were performed to assess the ability of silymarin to overcome the gamma rays-induced alterations on three related pivots: 1- Ovarian functions through the pituitary-gonadal hormones [follicle stimulating hormone (FSH), estradiol (E2) and progesterone. 2- Carbohydrate metabolism through pancreatic insulin associated with blood glucose and liver glycogen content. 3- Lipid profile including triglycerides, total cholesterol, high density lipoprotein (HDL-cholesterol) and low density lipoprotein (LDL-cholesterol). Fifty female rats were divided into 4 groups: 1- Control. 2- Whole body y-irradiated (I Gy). 3- Rats orally treated with silymarin (10 mg/100 g body weight) twice daily for one week. 4- Rats received silymarin as group (3) then irradiated 2 hours after the last dose of silymarin. Samples were taken 2 hours, 2 days and 2 weeks after silyrnarin gavage (group 3) or irradiation (groups 2 and 4). The results obtained showed lowered levels of FSH, E2 and P 4 as a result of ovarian dysfunction early after 2 hours and maximized after 2 weeks in irradiated rats. Plasma insulin and glucose levels were elevated with a decrease in glycogen content in liver. Also, plasma triglycerides, total cholesterol, LDL-cholesterol were elevated concomitant with decreased HDL-cholesterol level. Silymarin succeeded to ameliorate the disorders induced by irradiation and restored the majority of disturbed levels to control range. The present study designates that silymarin has a positive prophylactic effect against radiation-induced hazard on the ovarian function and speculates that silymarin could imitate a physiologic regulator for carbohydrate and lipid metabolism through several mentioned mechanisms

  17. Energy-containing beverages: reproductive hormones and ovarian function in the BioCycle Study123

    Schliep, Karen C; Mumford, Sunni L; Pollack, Anna Z; Perkins, Neil J; Ye, Aijun; Zhang, Cuilin J; Stanford, Joseph B; Porucznik, Christina A; Hammoud, Ahmad O; Wactawski-Wende, Jean

    2013-01-01

    Background: Energy-containing beverages are widely consumed among premenopausal women, but their association with reproductive hormones is not well understood. Objective: The objective was to assess the association of energy-containing beverages, added sugars, and total fructose intake with reproductive hormones among ovulatory cycles and sporadic anovulation in healthy premenopausal women. Design: Women (n = 259) in the BioCycle Study were followed for up to 2 menstrual cycles; they provided fasting blood specimens during up to 8 visits/cycle and four 24-h dietary recalls/cycle. Results: Women who consumed ≥1 cup (1 cup = 237 mL) sweetened soda/d had 16.3% higher estradiol concentrations compared with women who consumed less sweetened soda (86.5 pg/mL compared with 74.4 pg/mL, P = 0.01) after adjustment for age, BMI, race, dietary factors, and physical activity. Similarly elevated estradiol concentrations were found for ≥1 cup cola/d and noncola soda intake. Neither artificially sweetened soda nor fruit juice intake ≥1 cup/d was significantly associated with reproductive hormones. Added sugar above the average US woman's intake (≥73.2 g/d) or above the 66th percentile in total fructose intake (≥41.5 g/d) was associated with significantly elevated estradiol but not consistently across all models. No associations were found between beverages, added sugars, or total fructose intake and anovulation after multivariate adjustment. Conclusions: Even at moderate consumption amounts, sweetened soda is associated with elevated follicular estradiol concentrations among premenopausal women but does not appear to affect ovulatory function. Further research into the mechanism driving the association between energy-containing beverages and reproductive hormones, and its potential implications for women's health, is warranted. PMID:23364018

  18. Energy-containing beverages: reproductive hormones and ovarian function in the BioCycle Study.

    Schliep, Karen C; Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Perkins, Neil J; Ye, Aijun; Zhang, Cuilin J; Stanford, Joseph B; Porucznik, Christina A; Hammoud, Ahmad O; Wactawski-Wende, Jean

    2013-03-01

    Energy-containing beverages are widely consumed among premenopausal women, but their association with reproductive hormones is not well understood. The objective was to assess the association of energy-containing beverages, added sugars, and total fructose intake with reproductive hormones among ovulatory cycles and sporadic anovulation in healthy premenopausal women. Women (n = 259) in the BioCycle Study were followed for up to 2 menstrual cycles; they provided fasting blood specimens during up to 8 visits/cycle and four 24-h dietary recalls/cycle. Women who consumed ≥1 cup (1 cup = 237 mL) sweetened soda/d had 16.3% higher estradiol concentrations compared with women who consumed less sweetened soda (86.5 pg/mL compared with 74.4 pg/mL, P = 0.01) after adjustment for age, BMI, race, dietary factors, and physical activity. Similarly elevated estradiol concentrations were found for ≥1 cup cola/d and noncola soda intake. Neither artificially sweetened soda nor fruit juice intake ≥1 cup/d was significantly associated with reproductive hormones. Added sugar above the average US woman's intake (≥73.2 g/d) or above the 66th percentile in total fructose intake (≥41.5 g/d) was associated with significantly elevated estradiol but not consistently across all models. No associations were found between beverages, added sugars, or total fructose intake and anovulation after multivariate adjustment. Even at moderate consumption amounts, sweetened soda is associated with elevated follicular estradiol concentrations among premenopausal women but does not appear to affect ovulatory function. Further research into the mechanism driving the association between energy-containing beverages and reproductive hormones, and its potential implications for women's health, is warranted.

  19. Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

    Mowat, Freya M; Gonzalez, Francisco; Luhmann, Ulrich F O; Lange, Clemens A; Duran, Yanai; Smith, Alexander J; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

    2012-04-01

    Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Induction of Protective Genes Leads to Islet Survival and Function

    Hongjun Wang

    2011-01-01

    Full Text Available Islet transplantation is the most valid approach to the treatment of type 1 diabetes. However, the function of transplanted islets is often compromised since a large number of β cells undergo apoptosis induced by stress and the immune rejection response elicited by the recipient after transplantation. Conventional treatment for islet transplantation is to administer immunosuppressive drugs to the recipient to suppress the immune rejection response mounted against transplanted islets. Induction of protective genes in the recipient (e.g., heme oxygenase-1 (HO-1, A20/tumor necrosis factor alpha inducible protein3 (tnfaip3, biliverdin reductase (BVR, Bcl2, and others or administration of one or more of the products of HO-1 to the donor, the islets themselves, and/or the recipient offers an alternative or synergistic approach to improve islet graft survival and function. In this perspective, we summarize studies describing the protective effects of these genes on islet survival and function in rodent allogeneic and xenogeneic transplantation models and the prevention of onset of diabetes, with emphasis on HO-1, A20, and BVR. Such approaches are also appealing to islet autotransplantation in patients with chronic pancreatitis after total pancreatectomy, a procedure that currently only leads to 1/3 of transplanted patients being diabetes-free.

  1. Dendritic functionalization of monolayer-protected gold nanoparticles

    Cutler, Erin C.; Lundin, Erik; Garabato, B. Davis; Choi, Daeock; Shon, Young-Seok

    2007-01-01

    This paper describes the facile synthesis of nanoparticle-cored dendrimers (NCDs) and nanoparticle megamers from monolayer-protected gold clusters using either single or multi-step reactions. First, 11-mercaptoundecanoic acid/hexanethiolate-protected gold clusters were synthesized using the Schiffrin reaction followed by the ligand place-exchange reaction. A convergent approach for the synthesis of nanoparticle-cored dendrimers uses a single step reaction that is an ester coupling reaction of hydroxy-functionalized dendrons with carboxylic acid-functionalized gold clusters. A divergent approach, which is based on multi-step reactions, employs the repetition of an amide coupling reaction and a Michael addition reaction to build polyamidoamine dendritic architectures around a nanoparticle core. Nanoparticle megamers, which are large dendrimer-induced nanoparticle aggregates with an average diameter of more than 300 nm, were prepared by the amide coupling reaction between polyamiodoamine [G-2] dendrimers and carboxylic acid-functionalized gold clusters. 1 H NMR spectroscopy, FT-IR spectroscopy, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) were used for the characterization of these hybrid nanoparticles

  2. Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep

    Ryan Kate E

    2008-10-01

    Full Text Available Abstract Background The intracellular signalling mechanisms that regulate ovarian follicle development are unclear; however, we have recently shown differences in the Akt and Erk signalling pathways in dominant compared to subordinate follicles. The aim of this study was to investigate the effects of inhibiting Akt and Erk phosphorylation on IGF- and gonadotropin- stimulated granulosa and theca cell function in vitro, and on follicle development in vivo. Methods Bovine granulosa and theca cells were cultured for six days and stimulated with FSH and/or IGF, or LH in combination with PD98059 (Erk inhibitor and/or LY294002 (Akt inhibitor and their effect on cell number and hormone secretion (estradiol, activin-A, inhibin-A, follistatin, progesterone and androstenedione determined. In addition, ovarian follicles were treated in vivo with PD98059 and/or LY294002 in ewes on Day 3 of the cycle and follicles were recovered 48 hours later. Results We have shown that gonadotropin- and IGF-stimulated hormone production by granulosa and theca cells is reduced by treatment with PD98059 and LY294002 in vitro. Furthermore, treatment with PD98059 and LY294002 reduced follicle growth and oestradiol production in vivo. Conclusion These results demonstrate an important functional role for the Akt and Erk signalling pathways in follicle function, growth and development.

  3. SMIFH2-mediated mDia formin functional inhibition potentiates chemotherapeutic targeting of human ovarian cancer spheroids.

    Ziske, Megan A; Pettee, Krista M; Khaing, MaNada; Rubinic, Kaitlin; Eisenmann, Kathryn M

    2016-03-25

    Due to a lack of effective screening or prevention protocol for epithelial ovarian cancer (EOC), there is a critical unmet need to develop therapeutic interventions for EOC treatment. EOC metastasis is unique. Initial dissemination is not primarily hematogenous, yet is facilitated through shedding of primary tumor cells into the peritoneal fluid and accumulating ascites. Increasingly, isolated patient spheroids point to a clinical role for spheroids in EOC metastasis. EOC spheroids are highly invasive structures that disseminate upon peritoneal mesothelium, and visceral tissues including liver and omentum. Selection for this subset of chemoresistant EOC cells could influence disease progression and/or recurrence. Thus, targeting spheroid integrity/structure may improve the chemotherapeutic responsiveness of EOC. We discovered a critical role for mammalian Diaphanous (mDia)-related formin-2 in maintaining EOC spheroid structure. Both mDia2 and the related mDia1 regulate F-actin networks critical to maintain cell-cell contacts and the integrity of multi-cellular epithelial sheets. We investigated if mDia2 functional inhibition via a small molecule inhibitor SMIFH2 combined with chemotherapeutics, such as taxol and cisplatin, inhibits the viability of EOC monolayers and clinically relevant spheroids. SMIFH2-mediated mDia formin inhibition significantly reduced both ES2 and Skov3 EOC monolayer viability while spheroid viability was minimally impacted only at the highest concentrations. Combining either cisplatin or taxol with SMIFH2 did not significantly enhance the effects of either drug alone in ES2 monolayers, while Skov3 monolayers treated with taxol or cisplatin and SMIFH2 showed significant additive inhibition of viability. ES2 spheroids were highly responsive with clear additive anti-viability effects with dual taxol or cisplatin when combined with SMIFH2 treatments. While combined taxol with SMIFH2 in spheroids showed an additive effect relative to single

  4. Protective effects of dark chocolate on endothelial function and diabetes.

    Grassi, Davide; Desideri, Giovambattista; Ferri, Claudio

    2013-11-01

    Relationship between cocoa consumption and cardiovascular disease, particularly focusing on clinical implications resulting from the beneficial effects of cocoa consumption on endothelial function and insulin resistance. This could be of clinical relevance and may suggest the mechanistic explanation for the reduced risk of cardiovascular events reported in the different studies after cocoa intake. Increasing evidence supports a protective effect of cocoa consumption against cardiovascular disease. Cocoa and flavonoids from cocoa have been described to improve endothelial function and insulin resistance. A proposed mechanism could be considered in the improvement of the endothelium-derived vasodilator nitric oxide by enhancing nitric oxide synthesis or by decreasing nitric oxide breakdown. The endothelium plays a pivotal role in the arterial homeostasis, and insulin resistance is the most important pathophysiological feature in various prediabetic and diabetic states. Reduced nitric oxide bioavailability with endothelial dysfunction is considered the earliest step in the pathogenesis of atherosclerosis. Further, insulin resistance could account, at least in part, for the endothelial dysfunction. Endothelial dysfunction has been considered an important and independent predictor of future development of cardiovascular risk and events. Cocoa and flavonoids from cocoa might positively modulate these mechanisms with a putative role in cardiovascular protection.

  5. Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice.

    Elon C Roti Roti

    Full Text Available Increasing numbers of female patients survive cancer, but succumb to primary ovarian insufficiency after chemotherapy. We tested the hypothesis that Bortezomib (Bort protects ovaries from doxorubicin (DXR chemotherapy by treating female mice with Bort 1 hour prior to DXR. By preventing DXR accumulation in the ovary, Bort attenuated DXR-induced DNA damage in all ovarian cell types, subsequent γH2AFX phosphorylation, and resulting apoptosis in preantral follicles. Bort pretreatment extended the number of litters per mouse, improved litter size and increased pup weight following DXR treatment, thus increasing the duration of post-chemotherapy fertility and improving pup health. As a promising prophylactic ovoprotective agent, Bort does not interfere with cancer treatment, and is currently used as a chemotherapy adjuvant. Bort-based chemoprotection may preserve ovarian function in a non-invasive manner that avoids surgical ovarian preservation, thus diminishing the health complications of premature menopause following cancer treatment.

  6. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée (Margriet); M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×

  7. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  8. HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway.

    Ding, Chenyue; Zou, Qinyan; Wang, Fuxin; Wu, Huihua; Wang, Wei; Li, Hong; Huang, Boxian

    2018-01-01

    Human adipose-derived stem cells (hADSCs) are a potential therapeutic option for clinical applications because of their ability to produce cytokines and their capacity for trilineage differentiation. To date, few researchers have investigated the effects of hADSCs on natural ovarian aging (NOA). An NOA mouse model and human ovarian granule cells (hGCs) collected from individuals with NOA were prepared to assess the therapeutic effects and illuminate the mechanism of hADSCs in curing NOA. Enzyme-linked immunosorbent assay was used to detect the serum levels of sex hormones and antioxidative enzymes. The proliferation rate and marker expression level of hGCs were measured by flow cytometry (FACS). Cytokines were measured by a protein antibody array methodology. Western blot assays were used to determine the protein expression levels of SIRT1 and FOXO1. Our results showed that hADSCs displayed therapeutic activity against ovarian function in an NOA mouse model, increasing the proliferation rate and marker expression level of hGCs. Furthermore, the yields of hADSC-secreted HGF and bFGF were higher than those of other growth factors. FACS showed that combination treatment with the growth factors HGF and bFGF more strongly promoted proliferation and inhibited apoptosis in hGCs than HGF or bFGF treatment alone. FACS and ELISA revealed that the combination treatment with both growth factors inhibited oxidative stress more forcefully than treatments with only one of these growth factors. In addition, protein assays demonstrated that combination treatment with both growth factors suppressed oxidative stress by up-regulating the expression of SIRT1 and FOXO1. These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism by which HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway. © 2018 The Author

  9. Ovarian Autoantibodies Predict Ovarian Cancer

    2010-11-01

    Expression of thymidine 459 phosphorylase in epithelial ovarian cancer: correlation with angiogenesis, apoptosis , and 460 ultrasound-derived peak...trafficking, activation of S1P1 can promote or inhibit apoptosis of 41 immune cells depending on the balance of cytokines [7]. Knockout of S1P1 (LP(B1...EDG-1) in 42 mice is embryologically lethal [8]. S1P1 also has a role in inflammatory disease such as graft 43 versus host disease and multiple

  10. Tubal ligation and risk of ovarian cancer subtypes

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  11. Ovarian maldescent

    Trinidad, Carmen; Tardaguila, Francisco; Fernandez, Gabriel C.; Martinez, Concepcion; Chavarri, Elena; Rivas, Isabel [Departments of Radiology and Gynecology, Povisa Medical Center, Salamanca St. 5, 36211, Vigo (Pontevedra) (Spain)

    2004-05-01

    Undescended ovary is a rare disorder that can be associated with muellerian malformations. There is an unclear association with infertility and malignant disease. When an ovary is not in its normal location, it is sought in other locations above the pelvic brim. This is important in cases of undetermined cyclical abdominal pain, follicle aspiration and surgical castration. MRI has proven to be the best imaging method for finding an ovary in an anomalous position and for disregarding associated malformations. We report two patients with unilateral ovarian maldescent, one of them with Rokitansky-Kuester-Hauser syndrome. A review of the literature is included. (orig.)

  12. Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology.

    Dumont, Agathe; Dewailly, Didier; Plouvier, Pauline; Catteau-Jonard, Sophie; Robin, Geoffroy

    2016-12-01

    Ovulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established. To compare pulsatile GnRH therapy versus gonadotropins for ovulation induction in "FHA-PCOM" patients and to determine if one treatment strikes as superior to the other. A 12-year retrospective study, comparing 55 "FHA-PCOM" patients, treated either with GnRH therapy (38 patients, 93 cycles) or with gonadotropins (17 patients, 53 cycles). Both groups were similar, defined by low serum LH and E2 levels, low BMI, excessive follicle number per ovary and/or high serum AMH level. Ovulation rates were significantly lower with gonadotropins (56.6% versus 78.6%, p = 0.005), with more cancellation and ovarian hyper-responses (14% versus 34% per initiated cycle, p < 0.005). Pregnancy rates were significantly higher with GnRH therapy, whether per initiated cycle (26.9% versus 7.6%, p = 0.005) or per patient (65.8% versus 23.5%, p = 0.007). In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM.

  13. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.

    Jonathan Beesley

    Full Text Available Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC. We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.

  14. Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women

    El-Mazny A

    2016-11-01

    Full Text Available Akmal El-Mazny, Ahmed Kamel, Wafaa Ramadan, Sherine Gad-Allah, Suzy Abdelaziz, Ahmed M Hussein Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt Background: Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF. We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women. Materials and methods: In a case–control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI, flow index (FI, and vascularization FI (VFI values were measured in both groups. Results: There were no significant differences (P>0.05 in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries. Conclusion: Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism. Keywords: 3-D power Doppler, endometrioma, IVF, uterine and ovarian blood flow

  15. Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

    Farideh Zafari Zangeneh

    2012-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1 to estimate LC activity in rats with estradiol valerate (EV-induced PCO; (2 to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1 LC and yohimbine and 2 control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001, while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats.

  16. Functions of the National Board for Atomic Safety and Radiation Protection of the German Democratic Republic

    1985-01-01

    Functions of the National Board for Atomic Safety and Radiation Protection of the GDR are described considering the following aspects: Nuclear plant safety, nuclear safeguards, physical protection, safety in working areas, environmental protection including radioactive waste management, protection of man by medical supervision and dosimetry, further training, international co-operation and information. (author)

  17. Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome.

    Nybacka, Åsa; Carlström, Kjell; Ståhle, Agneta; Nyrén, Sven; Hellström, Per Martin; Hirschberg, Angelica Lindén

    2011-12-01

    To compare the influence of dietary management and/or physical exercise on ovarian function and metabolic variables in women with polycystic ovary syndrome (PCOS). Randomized 4-month trial with three interventions and a long-term follow-up. Women's health clinical research unit at a university hospital. Fifty-seven overweight/obese women with PCOS. Dietary management, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physical therapist. Ovarian function, endocrinologic, and metabolic status and body composition. On average, body mass index was reduced 6% by the dietary management, 3% by the exercise, and 5% by the combined interventions. Lower body fat and lean body mass were significantly decreased in the dietary groups, whereas upper body fat was lowered and lean body mass maintained by exercise alone. The menstrual pattern was significantly improved in 69% and ovulation confirmed in 34% of the patients, with no differences among the groups. The strongest predictor of resumed ovulation was a high serum level of insulin-like growth factor-binding protein 1 after the intervention. Follow-up of one-half of the patients for a median of 2.8 years revealed sustained weight reduction and improvement in menstrual pattern. Dietary management and exercise, alone or in combination, are equally effective in improving reproductive function in overweight/obese women with PCOS. The underlying mechanisms appear to involve enhanced insulin sensitivity. Supportive individualized programs for lifestyle change could exert long-term beneficial effects. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

    De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

    2000-05-01

    To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

  19. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10...

  20. Primary ovarian leiomyoma

    Mathew, Marian; Krolikowski, Anderzj; Al-Haddabi, Ibrahim; Nirmala, Vadakkepat

    2005-01-01

    Ovarian leiomyoma is a rare and incidentally detected neoplasm, clinically indistinguishable from subserous leiomyomas and ovarian fibromas, until histopathological confirmation. We present a case of leiomyoma arising primarily from the ovary in a 35 year old woman. (author)

  1. Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures

    Saw Yu-Ting

    2012-08-01

    Full Text Available Abstract Background Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures. Methods Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes. Results Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium. Conclusions The results of our study indicate that ALDH enzyme expression and activity may be associated

  2. Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures

    Saw, Yu-Ting; Thompson, David; Vasiliou, Vasilis; Berkowitz, Ross S; Ng, Shu-Wing; Yang, Junzheng; Ng, Shu-Kay; Liu, Shubai; Singh, Surendra; Singh, Margit; Welch, William R; Tsuda, Hiroshi; Fong, Wing-Ping

    2012-01-01

    Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures. Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes. Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium. The results of our study indicate that ALDH enzyme expression and activity may be associated with specific cell types in ovarian tumor tissues and vary according to

  3. Estimating health-state utility values for patients with recurrent ovarian cancer using Functional Assessment of Cancer Therapy – General mapping algorithms

    Hettle R

    2015-11-01

    Full Text Available Robert Hettle,1 John Borrill,2 Gaurav Suri,1 Jerome Wulff1 1Parexel Consulting, London, 2AstraZeneca, Macclesfield, UK Objectives: In the absence of EuroQol 5D data, mapping algorithms can be used to predict health-state utility values (HSUVs for use in economic evaluation. In a placebo-controlled Phase II study of olaparib maintenance therapy (NCT00753545, health-related quality of life was measured using the Functional Assessment of Cancer Therapy – Ovarian (FACT-O questionnaire. Our objective was to generate HSUVs from the FACT-O data using published mapping algorithms. Materials and methods: Algorithms were identified from a review of the literature. Goodness-of-fit and patient characteristics were compared to select the best-performing algorithm, and this was used to generate base-case HSUVs for the intention-to-treat population of the olaparib study and for patients with breast cancer antigen mutations. Results: Four FACT – General (the core component of FACT-O mapping algorithms were identified and compared. Under the preferred algorithm, treatment-related adverse events had no statistically significant effect on HSU (P>0.05. Discontinuation of the study treatment and breast cancer antigen mutation status were both associated with a reduction in HSUVs (–0.06, P=0.0009; and –0.03, P=0.0511, respectively. The mean HSUV recorded at assessment visits was 0.786. Conclusion: FACT – General mapping generated credible HSUVs for an economic evaluation of olaparib. As reported in other studies, different algorithms may produce significantly different estimates of HSUV. For this reason, it is important to test whether the choice of a specific algorithm changes the conclusions of an economic evaluation. Keywords: platinum sensitive ovarian cancer, EQ 5D, maintenance therapy, olaparib

  4. Ovarian cancer and smoking

    Beral, V; Gaitskell, K; Hermon, C

    2012-01-01

    Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....

  5. Ovarian failure following abdominal irradiation in childhood

    Shalet, S.M.; Beardwell, C.G.; Jones, P.H.M.; Pearson, D.; Orrell, D.H.

    1976-01-01

    Ovarian function was studied in 18 female patients treated for abdominal tumours during childhood. All received abdominal radiotherapy as part of their treatment and were studied between 1 and 26 years after irradiation. The serum gonadotrophins and oestradiol levels were consistent with ovarian failure in each case and there was a disproportionate elevation in serum follicle stimulating hormone (FSH) when compared to serum luteinizing hormone (LH) in 16. In 2 patients, the radiotherapeutic field extended downwards only as far as the sacral promontory. However, these 2 girls show similar evidence of ovarian failure to that in the other 16. (author)

  6. Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: Prevention by thiol group protecting agents

    Custodio, Jose B.A.; Cardoso, Carla M.P.; Santos, Maria S.; Almeida, Leonor M.; Vicente, Joaquim A.F.; Fernandes, Maria A.S.

    2009-01-01

    Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca 2+ -induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20 nmol/mg protein) induced Ca 2+ -dependent mitochondrial swelling, depolarization of membrane potential (ΔΨ), Ca 2+ release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40 nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the ΔΨ, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H 2 O 2 generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca 2+ -induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to

  7. Functional Fit Evaluation to Determine Optimal Ease Requirements in Canadian Forces Chemical Protective Gloves

    Tremblay-Lutter, Julie

    1995-01-01

    A functional fit evaluation of the Canadian Forces (CF) chemical protective lightweight glove was undertaken in order to quantify the amount of ease required within the glove for optimal functional fit...

  8. Protective Controller against Cascade Outages with Selective Harmonic Compensation Function

    Abramovich, B. N.; Kuznetsov, P. A.; Sychev, Yu A.

    2018-05-01

    The paper presents data on the power quality and development of protective devices for the power networks with distributed generation (DG).The research has shown that power quality requirements for DG networks differ from conventional ones. That is why main tendencies, protective equipment and filters should be modified. There isa developed algorithm for detection and prevention of cascade outages that can lead to the blackoutin DG networks and there was a proposed structural scheme for a new active power filter for selective harmonics compensation. Analysis of these theories and equipment led to the development of protective device that could monitor power balance and cut off non-important consumers. The last part of the article describes a microcontroller prototype developed for connection to the existing power station control center.

  9. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

    Overbeek Annelies

    2012-08-01

    Full Text Available Abstract Background Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS, the DCOG LATER-VEVO study. Methods The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75% and 333 (78% have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively. Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non- participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements. Discussion The DCOG LATER-VEVO study will provide valuable information about the

  10. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  11. Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an in Situ Protecting Groups.

    Ohta, Reiya; Fujioka, Hiromichi

    2017-01-01

    Recent progress in the chemoselective reduction and alkylation of carbonyl functions using our in situ protection method is described. Methods that enable reversal or control of the reactivity of a carbonyl functional group are potentially useful. They open up new areas of synthetic organic chemistry and change the concept of retrosynthesis because they remove the need for complicated protection/deprotection sequences. In this account, we discuss the strategy and applications of our in situ protection method using phosphonium salts.

  12. The inhibition of myometrial contractions by chlorinated herbicides (atrazine and linuron), and their disruptive effect on the secretory functions of uterine and ovarian cells in cow, in vitro.

    Wrobel, Michał H; Mlynarczuk, Jaroslaw

    2017-10-01

    The effect of atrazine and linuron, the popular and widely used chlorinated herbicides, on both myometrial contractions and secretory functions of bovine uterus and ovaries in vitro, was investigated. The pesticides inhibited (Pherbicides affected PGs secretion from myometrium and PGF2α from endometrium. Only the lowest dose of both tested compounds decreased PGE2 secretion from endometrium. The pesticides increased (P<0.05) the OT secretion from granulosa. However, only linuron stimulated (P<0.05) the OT secretion from the luteal cells, and it increased (P<0.05) the expression of mRNA for the OT precursor. Both compounds stimulated (P<0.05) the secretion of testosterone and atrazine increased (P<0.05) also the secretion of estradiol from the granulosa cells. While atrazine and linuron reduced (P<0.05) the progesterone secretion from the luteal cells. The data show that atrazine and linuron altered the secretory functions of ovarian cells and inhibited the myometrial contractions in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Effect of Docetaxel combined with Nedaplatin on serum LPA, CA199, CEA, Interleukin and immune function in patients with epithelial ovarian cancer

    Wan Wang

    2016-10-01

    Full Text Available Objective: To study the effect of Docetaxel combined with Nedaplatin on serum LPA, CA199, CEA, Interleukin and immune function in patients with epithelial ovarian cancer. Methods: A total of 78 EOC patients in our hospital from August 2012 to June 2015 were enrolled in this study. The subjects were divided into the control group (n=39 and the experiment group (n=39 randomly. The control group were treated with carboplatin, the experiment group were treated with docetaxel combined with nedaplatin. In the experimental group, 21 d for a course of treatment, in the control group, 28 d for a course of treatment, and the two groups were treated for 4 periods. The clinical efficacy after the treatment of the two groups were evaluated and compared. The changes of serum LPA, CA199, CEA and other related indexes were detected and compared between the two groups before and after chemotherapy. Results: There were no significantly differences of the serum LPA, CA199, CEA, IL (6,8,10 and immune function of the two groups before treatment. After treatment, two groups of patients with serum LPA, CA199, CEA and IL (6,8,10 were significantly lower in the treatment of, at the same time, the experimental group had the level of each index were significantly lower than that of the control group, the difference is statistically significant. Before treatment, two groups of patients` peripheral blood CD3+ , CD4+ and CD8+ cells accounted for ratio, the difference was not statistically significant; The peripheral blood CD3+ , CD4+ and CD8+ cells of the two groups after treatment were significantly lower than before treatment, and that of experiment were significantly higher than control group. Conclusion: Docetaxel combined with Nedaplatin chemotherapy can significantly reduce the serum LPA, CA199, CEA and IL (6,8,10 levels, improve peripheral blood CD3+ , CD4+ and CD8+ levels of patients with epithelial ovarian cancer, and it was worthy clinical application.

  14. Consumer Protection Strategies: A Literature Review and Synthesis. Improving the Consumer Protection Function in Postsecondary Education.

    Helliwell, Carolyn B.; Jung, Steven M.

    Summarized are the findings of an American Institutes for Research (AIR) project to field test a data capture and dissemination system that would provide information for improving consumer protection in postsecondary education. Presented is a discussion of the methodology used, examples of consumer abuses cited in the literature, an analysis of…

  15. Characterization of Ovarian Steroid Patterns in Female African Lions (Panthera leo), and the Effects of Contraception on Reproductive Function.

    Putman, Sarah B; Brown, Janine L; Franklin, Ashley D; Schneider, Emily C; Boisseau, Nicole P; Asa, Cheryl S; Pukazhenthi, Budhan S

    2015-01-01

    Because of poor reproduction after the lifting of an 8-year breeding moratorium, a biomedical survey of female lions in U.S. zoos was initiated in 2007. Fecal estrogen (FEM), progestagen (FPM) and glucocorticoid (FGM) metabolites were analyzed in samples collected 3-4 times per wk from 28 lions at 17 facilities (0.9-13.8 yr of age) for 4 mo-3.5 yr and body weights were obtained ~monthly from 17 animals at eight facilities (0.0-3.0 yr of age). Based on FEM, estrous cycle length averaged 17.5 ± 0.4 d in duration, with estrus lasting 4.4 ± 0.2 d. All but one female exhibited waves of estrogenic activity indicative of follicular activity; however, not all females expressed estrous behaviors (73%), suggesting silent estrus was common. Female lions experienced puberty earlier than expected; waves of estrogenic activity were observed as young as 1.1 yr of age, which may be related to a faster growth rate of captive vs. wild lions. Mean gestation length was 109.5 ± 1.0 d, whereas the non-pregnant luteal phase was less than half (46.0 ± 1.2 d). Non-mating induced increases in FPM were observed in 33% of females housed without a male, consistent with spontaneous ovulation. A number of study animals had been contracepted, and the return to cyclicity after treatment withdrawal, while variable, was ~4.0 yr and longer than the 1-yr expected efficacy, especially for those implanted with Suprelorin. For FGM, there were no differences in overall, baseline or peak mean concentrations among the age groups or across seasons, nor were there any relationships between reproductive parameters and FGM concentrations. Overall, results suggest that poor reproduction in lions after the breeding moratorium was not related to altered adrenal or ovarian steroid activity, but for some females may have been a consequence of individual institutions' management decisions.

  16. Characterization of Ovarian Steroid Patterns in Female African Lions (Panthera leo), and the Effects of Contraception on Reproductive Function

    Putman, Sarah B.; Brown, Janine L.; Franklin, Ashley D.; Schneider, Emily C.; Boisseau, Nicole P.; Asa, Cheryl S.; Pukazhenthi, Budhan S.

    2015-01-01

    Because of poor reproduction after the lifting of an 8-year breeding moratorium, a biomedical survey of female lions in U.S. zoos was initiated in 2007. Fecal estrogen (FEM), progestagen (FPM) and glucocorticoid (FGM) metabolites were analyzed in samples collected 3–4 times per wk from 28 lions at 17 facilities (0.9–13.8 yr of age) for 4 mo—3.5 yr and body weights were obtained ~monthly from 17 animals at eight facilities (0.0–3.0 yr of age). Based on FEM, estrous cycle length averaged 17.5 ± 0.4 d in duration, with estrus lasting 4.4 ± 0.2 d. All but one female exhibited waves of estrogenic activity indicative of follicular activity; however, not all females expressed estrous behaviors (73%), suggesting silent estrus was common. Female lions experienced puberty earlier than expected; waves of estrogenic activity were observed as young as 1.1 yr of age, which may be related to a faster growth rate of captive vs. wild lions. Mean gestation length was 109.5 ± 1.0 d, whereas the non-pregnant luteal phase was less than half (46.0 ± 1.2 d). Non-mating induced increases in FPM were observed in 33% of females housed without a male, consistent with spontaneous ovulation. A number of study animals had been contracepted, and the return to cyclicity after treatment withdrawal, while variable, was ~4.0 yr and longer than the 1-yr expected efficacy, especially for those implanted with Suprelorin. For FGM, there were no differences in overall, baseline or peak mean concentrations among the age groups or across seasons, nor were there any relationships between reproductive parameters and FGM concentrations. Overall, results suggest that poor reproduction in lions after the breeding moratorium was not related to altered adrenal or ovarian steroid activity, but for some females may have been a consequence of individual institutions’ management decisions. PMID:26460849

  17. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAS

    2016-04-01

    chemoresistant cancer cells can sensitize chemoresistant ovarian tumors to cisplatin treatment and inhibit ovarian cancer dissemination in a pre...determine the mechanism by which miR-181a was regulating the emergence of these CICs. What opportunities for training and professional development has...also perform data analysis to correlate those miRNAs expression with patient response to cisplatin and other clinicopathological parameters. She

  18. Power unit impedance and distance protection functions during faults in the external power grid

    Marcin Lizer

    2012-12-01

    Full Text Available This paper presents the problem of the risk of an unnecessary tripping of a generation unit’s underimpedance protection functions in circumstances of generator power swings following elimination of long-lasting fault in the external power grid. The fi rst part describes typical solutions of a generator impedance protection function (21e and unit distance protection function (21s. Starting characteristics of these protection functions are shown, as well as their typical operating logics and ways of calculating their settings. Then exemplary (the most common solutions of unit under-impedance relays power swing blocking functions are described. Following this introduction, the issues of the threat of unnecessary operation of fast-tripping protection zones of 21e and 21s protection functions are described, which arises in the circumstances of generator asynchronous power swings occurring after elimination of long-lasting faults in the grid supplied by the power unit. The paper also shows that the available power swing blocking functions may not be able to correctly detect the described conditions, thus allowing the unnecessary operation of under-impedance relays. How an impedance calculation algorithm affects the impedance trajectory seen by a protection relay is also resented.

  19. The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance.

    Sacchinelli, Angela; Venturella, Roberta; Lico, Daniela; Di Cello, Annalisa; Lucia, Antonella; Rania, Erika; Cirillo, Roberto; Zullo, Fulvio

    2014-01-01

    Objective. Substances such as inositol and N-acetylcysteine (NAC) have been recently shown to be effective in treatment of PCOS patients. The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A) and absent in 47 (B). The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint. Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed. Conclusions. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients. Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index.

  20. The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance

    Angela Sacchinelli

    2014-01-01

    Full Text Available Objective. Substances such as inositol and N-acetylcysteine (NAC have been recently shown to be effective in treatment of PCOS patients. The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A and absent in 47 (B. The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint. Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed. Conclusions. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients. Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index.

  1. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol.

    Laganà, Antonio Simone; Barbaro, Luisa; Pizzo, Alfonsa

    2015-05-01

    To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS). We enrolled 48 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. These patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We analyzed pre-treatment and post-treatment BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, DHEA-S, Δ-4-androstenedione, SHBG, prolactin, glucose/IRI ratio, HOMA index, and resumption of regular menstrual cycles. We evidenced a statistically significant reduction of systolic blood pressure, Ferriman-Gallwey score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin, and HOMA Index; in the same patients, we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (62.5%; p treatment menstrual cycle regularization. D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.

  2. Polycystic ovarian syndrome

    Nina Madnani

    2013-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  3. Polycystic ovarian syndrome.

    Madnani, Nina; Khan, Kaleem; Chauhan, Phulrenu; Parmar, Girish

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  4. Premature ovarian failure

    Persani Luca

    2006-04-01

    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  5. Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome

    Nylander, Malin; Frøssing, Signe; Clausen, Helle V.

    2017-01-01

    Polycystic ovary syndrome (PCOS) encompasses an ovarian and a metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) analogues facilitate weight loss and ameliorate metabolic dysfunction in overweight women with PCOS, but their effect on ovarian dysfunction is scarcely reported. In a double......-blind, randomized trial, 72 women with PCOS were allocated to intervention with the GLP-1 analogue liraglutide or placebo (1.8 mg/day), in a 2:1 ratio. At baseline and 26-week follow-up, bleeding pattern, levels of AMH, sex hormones and gonadotrophins were assessed and ovarian morphology evaluated. Liraglutide...... of ovarian function in overweight women with PCOS, and might be a possible intervention....

  6. Statutory Instrument no. 1230, The National Radiological Protection Board (Extension of Functions) Order 1974

    1974-01-01

    This Order, which came into operation of 1st August 1974, extends the functions and powers of the National Radiological Protection Board, which was established by the Radiological Protection Act 1970 so as to cover research and the giving of advice on the dangers of radiation which is electromagnetic but not ionizing. (NEA) [fr

  7. Improving Mitochondrial Function Protects Bumblebees from Neonicotinoid Pesticides.

    Michael B Powner

    Full Text Available Global pollination is threatened by declining insect pollinator populations that may be linked to neonicotinoid pesticide use. Neonicotinoids over stimulate neurons and depolarize their mitochondria, producing immobility and death. However, mitochondrial function can be improved by near infrared light absorbed by cytochrome c oxidase in mitochondrial respiration. In flies, daily exposure to 670nm light throughout life increases average lifespan and aged mobility, and reduces systemic inflammation. Here we treat bumble bees with Imidacloprid a common neonicotinoid. This undermined ATP and rapidly induced immobility and reduced visual function and survival. Bees exposed to insecticide and daily to 670nm light showed corrected ATP levels and significantly improved mobility allowing them to feed. Physiological recordings from eyes revealed that light exposure corrected deficits induced by the pesticide. Overall, death rates in bees exposed to insecticide but also given 670nm light were indistinguishable from controls. When Imidacloprid and light exposure were withdrawn, survival was maintained. Bees and insects generally cannot see deep red light so it does not disturb their behaviour. Hence, we show that deep red light exposure that improves mitochondrial function, reverses the sensory and motor deficits induced by Imidacloprid. These results may have important implications as light delivery is economic and can be placed in hives/colonies.

  8. Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer.

    Andreas Rump

    2016-08-01

    Full Text Available The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription. In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense, all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance. Ten out of eleven mutations that were tested exemplarily in cell-based functional assays exert diminished excision repair efficiency and/or decreased transcriptional activation capability. In order to provide evidence for BC/OC predisposition, we performed familial segregation analyses and screened ethnically matching controls. However, unlike the recently published RECQL example, none of our recurrent ERCC2 mutations showed convincing co-segregation with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly, we detected that some deleterious founder mutations had an unexpectedly high frequency of > 1% in the corresponding populations, suggesting that either homozygous carriers are not clinically recognized or homozygosity for these mutations is embryonically lethal. In conclusion, we provide a useful resource on the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as our key finding, we demonstrate the complexity of correct interpretation for the discovery of "bonafide" breast cancer susceptibility genes.

  9. Protective

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  10. A NANOS3 mutation linked to protein degradation causes premature ovarian insufficiency

    Wu, X; Wang, B; Dong, Z; Zhou, S; Liu, Z; Shi, G; Cao, Y; Xu, Y

    2013-01-01

    Primary ovarian insufficiency (POI), or premature ovarian failure, is defined as the cessation of ovarian function before the age of 40. An insufficient ovarian follicle pool derived from primordial germ cells (PGCs) is an important cause of POI. Although the Nanos gene family is known to be required for PGC development and maintenance in diverse model organisms, the relevance of this information to human biology is not yet clear. In this study, we screened the coding regions of the NANOS1, N...

  11. Ectopic ovarian pregnancy

    Sachdev, P.S.; Jatoi, N.; Memon, R.A.; Sachdev, C.S.

    2003-01-01

    A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy. (author)

  12. Successful ovarian autotransplant with no vascular reanastomosis in rats.

    Barros, Flávio S V; de Oliveira, Rodrigo M; Alves, Felipe M T; Sampaio, Marcos; Geber, Selmo

    2008-12-15

    Preservation of ovarian functions in woman with premature ovarian failure remains an issue in reproductive medicine. Hormone replacement therapy for maintaining endocrine functions, and cryopreservation of embryos or oocytes for those who wish pregnancy, are some of the choices. However, ovarian transplantation is a more physiological alternative, although problems related to ovarian ischemia have been reported. Herein, we investigated the viability of autologous transplantation of the ovarian tissue into the rat peritoneum, without vascular reanastomosis. Twenty animals in the study group had both ovaries excised, and each ovary was dissected into two halves. A half of an ovary was autotransplanted to the peritoneal surface, closely located to the left epigastric vessels. This simple procedure does not require surgical vascular reanastomosis while it maintains appropriate follicular growth and therefore should be further considered as an alternative for women undergoing oophorectomy, not only to maintain endocrine functions but also for fertility preservation.

  13. Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

    Axelrod, Joshua; Delaney, Joe

    2017-07-01

    Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

  14. Functional recovery of denervated skeletal muscle with sensory or mixed nerve protection: a pilot study.

    Qing Tian Li

    Full Text Available Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection or sural nerve (sensory protection. The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.

  15. Prevention of ovarian cancer.

    Hanna, Louise; Adams, Malcolm

    2006-04-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

  16. Treatment Results of Ovarian Dysqerminoma

    Chung, Eun Ji; Suh, Chang Ok; Seong, Jin Sil; Keum, Ki Chang; Kim, Gwi Eon

    1996-01-01

    progressed carcinomatosis at 11 months after salvage radiotherapy. The other two patients with recurrence were salvaged with chemotherapy (1 patient) or re-operation (1 patient). Twenty eight patients remained alive without disease at last follow up, so the 5 year local control rate and 5 year overall survival rate for all groups were 96.6% (28/29), respectively. Among thirteen patients with stage la unilateral tumors seven patients were treated with postoperative radiotherapy and the other six patients were treated with unilateral salpingo-oophorectomy alone. Five patients who did not received radiotherapy developed local failure but all of the recurrent ovarian dysgerminomas were salvaged with radiotherapy, chemotherapy or re-operation, So all the 13 patients with stage la ovarian dysgerminoma were free of disease from 20-201 months (median 80 months). Conclusion : The authors consider external irradiation to be an effective treatment as a complement to surgery in ovarian dysgerminoma. For those patients with disease presenting in stage la tumors who wish to maintain fertility, unilateral salpingo-oophorectomy alone may be curative and spare ovarian function considering excellent salvage rate of recurrent ovarian dysgerminoma in present study

  17. Development of A Mouse Model of Menopausal Ovarian Cancer

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  18. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo

    2002-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  19. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo C

    2004-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  20. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo C

    2005-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  1. Characterization of the Chicken Ovarian Cancer Model

    Rodriguez, Gustavo

    2003-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  2. Characterization of the Chicken Ovarian Cancer Model

    Rodriquez, Gustavo

    2001-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  3. Ovarian sex hormones modulate compulsive, affective and cognitive functions in a non-induced mouse model of obsessive-compulsive disorder

    Swarup Mitra

    2016-11-01

    Full Text Available There is currently a lack of understanding how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female OCD patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX, which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After seven days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2 or progesterone (P4 could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background.

  4. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  5. A COMPREHENSIVE MODEL FOR THE POWER TRANSFORMER DIGITAL DIFFERENTIAL PROTECTION FUNCTIONING RESEARCH

    Yu. V. Rumiantsev

    2016-01-01

    Full Text Available This article presents a comprehensive model for the two-winding power transformer digital differential protection functioning research. Considered comprehensive model is developed in MatLab-Simulink dynamic simulation environment with the help of SimPowerSystems component library and includes the following elements: power supply, three-phase power transformer, wye-connected current transformers and two-winding power transformer digital differential protection model. Each element of the presented model is described in the degree sufficient for its implementation in the dynamic simulation environment. Particular attention is paid to the digital signal processing principles and to the ways of differential and restraining currents forming of the considered comprehensive model main element – power transformer digital differential protection. With the help of this model the power transformer digital differential protection functioning was researched during internal and external faults: internal short-circuit, external short-circuit with and without current transformers saturation on the power transformer low-voltage side. Each experiment is illustrated with differential and restraining currents waveforms of the digital differential protection under research. Particular attention was paid to the digital protection functioning analysis during power transformer abnormal modes: overexcitation and inrush current condition. Typical current waveforms during these modes were showed and their harmonic content was investigated. The causes of these modes were analyzed in details. Digital differential protection blocking algorithms based on the harmonic content were considered. Drawbacks of theses algorithms were observed and the need of their further technical improvement was marked.

  6. The Relationship between Physical Activity and Thermal Protective Clothing on Functional Balance in Firefighters

    Kong, Pui W.; Suyama, Joe; Cham, Rakie; Hostler, David

    2012-01-01

    We investigated the relationship between baseline physical training and the use of firefighting thermal protective clothing (TPC) with breathing apparatus on functional balance. Twenty-three male firefighters performed a functional balance test under four gear/clothing conditions. Participants were divided into groups by physical training status,…

  7. Premature ovarian failure and ovarian autoimmunity

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

  8. Left ventricular contractile function after distal protection in primary percutaneous coronary intervention Results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial

    Kofoed, K F; Kelbæk, H; Thuesen, L

    2011-01-01

    Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function.......Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function....

  9. Studies on the protection effects of functional foods for skin immune system from radiation damage

    Yee, Sung Tae; Shin, Seong Hae; Kim, Do Sun; Heo, Ji Yun; Kang, Hye In

    2007-07-01

    We evaluated the protective effects of pilot products (HemoHIM and HemoTonic) on the UV-induced skin immune damages as the following. · Protective effects of HemoHIM and HemoTonic against UV using contact hypersensitivity model - Protection against depression of contact hypersensitivity by administration and skin application of HemoHIM and HemoTonic - Induction of dendritic cell differentiation and maturation by HemoHIM and HemoTonic treatment - Improvement of antigen-presenting activity of dedritic cells by HemoHIM and HemoTonic treatment · Protective effects of HemoHIM and HemoTonic on skin immune system against UV-irradiation - Protection of antigen-presenting activity of dendritic cells under UV-irradiation - In vivo protection of antigen-presenting activity of Langerhans cells in UV-irradiated mice · Protective effects of HemoHIM on UV-induced apoptosis of dendritic cells - Inhibition of cell membrane change, mitochondrial potential change, SubG1 cell population, nuclear condensation, and DNA fragmentation in UV-irradiated dendritic cells · Anti-allergic effects of HemoHIM and HemoTonic in human adipocyte HMC-1 cells - Inhibition of allergic histamine release from adipocytes - Inhibition of secretion of inflammatory cytokines (IL-6, IL-8, TNF-α, GM-CSF) - Inhibition of c-kit, tryptase, FcεRI mRNA expression From these results, the developed functional food products (HemoHIM, HemoTonic) showed the protection and recovery of the immune functions in the UV-irradiated skin. It is suggested that these products may be used as a new functional food or cosmetic material for the protection of skin damage and the promotion of recovery

  10. Studies on the protection effects of functional foods for skin immune system from radiation damage

    Yee, Sung Tae; Shin, Seong Hae; Kim, Do Sun; Heo, Ji Yun; Kang, Hye In [Sunchon National University, Sunchon (Korea, Republic of)

    2007-07-15

    We evaluated the protective effects of pilot products (HemoHIM and HemoTonic) on the UV-induced skin immune damages as the following. centre dot Protective effects of HemoHIM and HemoTonic against UV using contact hypersensitivity model - Protection against depression of contact hypersensitivity by administration and skin application of HemoHIM and HemoTonic - Induction of dendritic cell differentiation and maturation by HemoHIM and HemoTonic treatment - Improvement of antigen-presenting activity of dedritic cells by HemoHIM and HemoTonic treatment centre dot Protective effects of HemoHIM and HemoTonic on skin immune system against UV-irradiation - Protection of antigen-presenting activity of dendritic cells under UV-irradiation - In vivo protection of antigen-presenting activity of Langerhans cells in UV-irradiated mice centre dot Protective effects of HemoHIM on UV-induced apoptosis of dendritic cells - Inhibition of cell membrane change, mitochondrial potential change, SubG1 cell population, nuclear condensation, and DNA fragmentation in UV-irradiated dendritic cells centre dot Anti-allergic effects of HemoHIM and HemoTonic in human adipocyte HMC-1 cells - Inhibition of allergic histamine release from adipocytes - Inhibition of secretion of inflammatory cytokines (IL-6, IL-8, TNF-alpha, GM-CSF) - Inhibition of c-kit, tryptase, FcepsilonRI mRNA expression From these results, the developed functional food products (HemoHIM, HemoTonic) showed the protection and recovery of the immune functions in the UV-irradiated skin. It is suggested that these products may be used as a new functional food or cosmetic material for the protection of skin damage and the promotion of recovery

  11. Antenatal hypoxia induces programming of reduced arterial blood pressure response in female rat offspring: role of ovarian function.

    DaLiao Xiao

    Full Text Available In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring.

  12. Polyurethane Functional Coatings for Protection of Different Surfaces from Aggressive Environmental Factors

    Savelyev, U.V., Markovska, L.A., Robota, L.P., Parkhomenko, N.I., and Savelyeva, O.O.

    2014-05-01

    Full Text Available New polyurethane compositions (PC as multifunctional protective materials that can serve as coatings or binders or impregnating materials have been created. PC have high adhesion values and the PC-based materials are waterproof and resistant to aggressive biotic (abiotic and technogenic factors (biocorrosion, UV radiation, chemical agents. Putting active compounds into the polymer macrochain prolongs the protection functions of the materials. This is their advantage to existing materials.

  13. Concepts on integration of physical protection and material accounting functions in a safeguards system

    Reynolds, D.A.

    1981-01-01

    Concepts on integration of physical protection and material accounting systems to enhance overall safeguards capability are developed and presented. These concepts identify ways in which material accounting systems can be used to enable effective monitoring of authorized movement of nuclear material through physical protection boundaries. Concepts are also discussed for monitoring user access to nuclear material and for tagging user identification to material accounting transactions through physical protection functions. These result in benefits in detecting diversion and in positively tracing material movement. Finally, coordination of safeguards information from both subsystems in such an integrated system through a safeguards coordination center is addressed with emphasis on appropriate response in case of discrepancies

  14. Ovarian Cancer and Comorbidity

    Noer, Mette Calundann; Sperling, Cecilie Dyg; Ottesen, Bent

    2017-01-01

    OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish...... ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test...... and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox...

  15. Ovarian Cancer FAQ

    ... vein thrombosis (DVT) , heart attack, and stroke. Current theories suggest that some types of ovarian cancer may ... Annual Meeting CME Overview CREOG Meetings Calendar Congressional Leadership Conference Advocacy Legislative Priorities GR & Outreach State Advocacy ...

  16. Management of ovarian cysts

    Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul

    2004-01-01

    BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

  17. Primary ovarian malignant melanoma

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  18. Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

    Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

    2017-09-01

    Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither

  19. Regulatory T Cells in Human Ovarian Cancer

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  20. Barrier function test: Laboratory evaluation of the protective function of some barrier creams against cashewnut shell oil

    Pasricha J

    1991-01-01

    Full Text Available A barrier function test has been designed to screen the protective capacity of a cream against the cauterizing effect of cashew nut shell oil (CNSO on the skin. The test consists of applying the barrier cream on a 5 cm circular area of skin on the back of a human volunteer and then at its centre applying a 1 cm sq Whatman no. 3 paper disc soaked in the CNSO for 15 minutes and looking for the evidence of cauterization reaction after 48 hours. Of the various creams containing a variety of paraffins, bees wax, polyethylene glycols, methyl cellulose gel, and petrolatum, only polyethylene glycol (PEG cream was found to afford adequate protection against cashew nut shell oil. Addition of 10% zinc oxide or 10% kaolin to the PEG cream did not seem to afford any additional protection. Castor oil already being used by the workers was found to be inferior to the PEG cream.

  1. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

    Angelica B Bernal

    Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

  2. Construction, expression, and function of 6B11ScFv-mIL-12, a fusion protein that attacks human ovarian carcinoma.

    Cheng, Hongyan; Ye, Xue; Chang, Xiaohong; Ma, Ruiqiong; Cong, Xu; Niu, Yidong; Zhang, Menglei; Liu, Kai; Cui, Heng; Sang, Jianli

    2015-04-01

    We previously produced an anti-idiotypic monoclonal antibody, 6B11, which mimics ovarian cancer antigen CA166-9 and induces cellular and humoral immunity. Here, to enhance the immunogenicity of 6B11, we constructed the 6B11ScFv-mIL-12 fusion protein (FP), by fusing single-chain fragment of 6B11 variable region (6B11ScFv) with mouse interleukin-12 (mIL-12), which was expressed in eukaryotic 293EBNA cells transfected with pSBI vectors. A binding activity assay showed 6B11ScFv-mIL-12 to have activities of both 6B11 and mIL-12-it specifically bound both ovarian monoclonal antibody COC166-9 and rabbit anti-mouse IL-12 antibody. The immune activity assay showed 6B11ScFv-mIL-12 to promote proliferation of lymphocytes stimulated by phytohemagglutinin, increase the absolute numbers and percentages of CD3(-)/CD56(+) natural killer cells and CD3(+)/CD56(+) natural killer T cells among peripheral lymphocytes, and increase interferon-γ. The FP was specifically cytotoxic to the CA166-9(+) ovarian cancer cell lines HOC1A and SKOV3 and inhibited growth of ID8 subcutaneous tumors in C57BL/6J mice. This study provides an experimental basis for clinical use of 6B11ScFv-mIL-12 in ovarian cancer therapy. To our knowledge, this is the first report of a fusion protein from an anti-idiotypic antibody and IL-12.

  3. Ovarian failure due to cancer treatment and fertility preservation options

    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  4. Form or function: Does focusing on body functionality protect women from body dissatisfaction when viewing media images?

    Mulgrew, Kate E; Tiggemann, Marika

    2018-01-01

    We examined whether shifting young women's ( N =322) attention toward functionality components of media-portrayed idealized images would protect against body dissatisfaction. Image type was manipulated via images of models in either an objectified body-as-object form or active body-as-process form; viewing focus was manipulated via questions about the appearance or functionality of the models. Social comparison was examined as a moderator. Negative outcomes were most pronounced within the process-related conditions (body-as-process images or functionality viewing focus) and for women who reported greater functionality comparison. Results suggest that functionality-based depictions, reflections, and comparisons may actually produce worse outcomes than those based on appearance.

  5. Protecting cells by protecting their vulnerable lysosomes: Identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress.

    Pascua-Maestro, Raquel; Diez-Hermano, Sergio; Lillo, Concepción; Ganfornina, Maria D; Sanchez, Diego

    2017-02-01

    Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge. The protecting role of ApoD is known from cellular to organism level, and many of its downstream effects, including optimization of autophagy upon neurodegeneration, have been described. However, we still cannot assign a cellular mechanism to ApoD gene that explains how this protection is accomplished. Here we perform a comprehensive analysis of ApoD intracellular traffic and demonstrate its role in lysosomal pH homeostasis upon paraquat-induced oxidative stress. By combining single-lysosome in vivo pH measurements with immunodetection, we demonstrate that ApoD is endocytosed and targeted to a subset of vulnerable lysosomes in a stress-dependent manner. ApoD is functionally stable in this acidic environment, and its presence is sufficient and necessary for lysosomes to recover from oxidation-induced alkalinization, both in astrocytes and neurons. This function is accomplished by preventing lysosomal membrane permeabilization. Two lysosomal-dependent biological processes, myelin phagocytosis by astrocytes and optimization of neurodegeneration-triggered autophagy in a Drosophila in vivo model, require ApoD-related Lipocalins. Our results uncover a previously unknown biological function of ApoD, member of the finely regulated and evolutionary conserved gene family of extracellular Lipocalins. They set a lipoprotein-mediated regulation of lysosomal membrane integrity as a new mechanism at the hub of many cellular

  6. Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

    Zelieann R. Craig

    2010-01-01

    Full Text Available Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months C57BL/6Hsd female mice were divided into: CON (vehicle, VCD (160 mg/kg; 15d, or OVX (ovariectomized. Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05 than baseline, starting 1 month after ovarian failure in VCD and OVX mice. Following μCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.

  7. Functional issues and environmental qualification of digital protection systems of advanced light-water nuclear reactors

    Korsah, K.; Clark, R.L.; Wood, R.T. [Oak Ridge National Lab., TN (United States)

    1994-04-01

    Issues of obsolescence and lack of infrastructural support in (analog) spare parts, coupled with the potential benefits of digital systems, are driving the nuclear industry to retrofit analog instrumentation and control (I&C) systems with digital and microprocessor-based systems. While these technologies have several advantages, their application to safety-related systems in nuclear power plants raises key issues relating to the systems` environmental qualification and functional reliability. To bound the problem of new I&C system functionality and qualification, the authors focused this study on protection systems proposed for use in ALWRs. Specifically, both functional and environmental qualification issues for ALWR protection system I&C were addressed by developing an environmental, functional, and aging data template for a protection division of each proposed ALWR design. By using information provided by manufacturers, environmental conditions and stressors to which I&C equipment in reactor protection divisions may be subjected were identified. The resulting data were then compared to a similar template for an instrument string typically found in an analog protection division of a present-day nuclear power plant. The authors also identified fiber-optic transmission systems as technologies that are relatively new to the nuclear power plant environment and examined the failure modes and age-related degradation mechanisms of fiber-optic components and systems. One reason for the exercise of caution in the introduction of software into safety-critical systems is the potential for common-cause failure due to the software. This study, however, approaches the functionality problem from a systems point of view. System malfunction scenarios are postulated to illustrate the fact that, when dealing with the performance of the overall integrated system, the real issues are functionality and fault tolerance, not hardware vs. software.

  8. Functional issues and environmental qualification of digital protection systems of advanced light-water nuclear reactors

    Korsah, K.; Clark, R.L.; Wood, R.T.

    1994-04-01

    Issues of obsolescence and lack of infrastructural support in (analog) spare parts, coupled with the potential benefits of digital systems, are driving the nuclear industry to retrofit analog instrumentation and control (I ampersand C) systems with digital and microprocessor-based systems. While these technologies have several advantages, their application to safety-related systems in nuclear power plants raises key issues relating to the systems' environmental qualification and functional reliability. To bound the problem of new I ampersand C system functionality and qualification, the authors focused this study on protection systems proposed for use in ALWRs. Specifically, both functional and environmental qualification issues for ALWR protection system I ampersand C were addressed by developing an environmental, functional, and aging data template for a protection division of each proposed ALWR design. By using information provided by manufacturers, environmental conditions and stressors to which I ampersand C equipment in reactor protection divisions may be subjected were identified. The resulting data were then compared to a similar template for an instrument string typically found in an analog protection division of a present-day nuclear power plant. The authors also identified fiber-optic transmission systems as technologies that are relatively new to the nuclear power plant environment and examined the failure modes and age-related degradation mechanisms of fiber-optic components and systems. One reason for the exercise of caution in the introduction of software into safety-critical systems is the potential for common-cause failure due to the software. This study, however, approaches the functionality problem from a systems point of view. System malfunction scenarios are postulated to illustrate the fact that, when dealing with the performance of the overall integrated system, the real issues are functionality and fault tolerance, not hardware vs. software

  9. Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

    Paramu, Sobhana

    2016-12-01

    Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

  10. Premature ovarian failure and ovarian autoimmunity

    Schoemaker, Joop; Drexhage, Hemmo; Hoek, Annemieke

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic...

  11. Self-Injurious Behavior and Functional Analysis: Where Are the Descriptions of Participant Protections?

    Weeden, Marc; Mahoney, Amanda; Poling, Alan

    2010-01-01

    This study examined the reporting of participant protections in studies involving functional analysis and self-injurious behavior and published from 1994 through 2008. Results indicated that session termination criteria were rarely reported and other specific participant safeguards were seldom described. The absence of such information in no way…

  12. Risk and protective factors of different functional trajectories in older persons : Are these the same?

    Kempen, G.I.; Ranchor, A.V.; van Sonderen, E.; van Jaarsveld, C.H.; Sanderman, R.

    We examined whether risk and protective factors of different functional trajectories were the same in 1,765 Dutch older persons. We assessed disability in 1993 and reassessed it in 2001. For 2001 as compared with 1993, we distinguished three trajectory groups: substantially poorer, somewhat poorer,

  13. Multiple metastases from ovarian cancer

    Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.

  14. Ovarian ageing: the role of mitochondria in oocytes and follicles.

    May-Panloup, Pascale; Boucret, Lisa; Chao de la Barca, Juan-Manuel; Desquiret-Dumas, Valérie; Ferré-L'Hotellier, Véronique; Morinière, Catherine; Descamps, Philippe; Procaccio, Vincent; Reynier, Pascal

    2016-11-01

    the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality. A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Minimising farm crop protection pressure supported by the multiple functionalities of the DISCUSS indicator set.

    Wustenberghs, Hilde; Fevery, Davina; Lauwers, Ludwig; Marchand, Fleur; Spanoghe, Pieter

    2018-03-15

    Sustainable crop protection (SCP) has many facets. Farmers may therefore perceive transition to SCP as very complex. The Dual Indicator Set for Crop Protection Sustainability (DISCUSS) can handle this complexity. To provide targeted support throughout the transition to SCP, complexity capture must be synchronised with the time course of on-farm decision-making. Tool use must be tuned to farmer awareness and appropriate level of data in consecutive stages. This paper thus explores the potential functionalities of DISCUSS in relation to both complexity and time. Results from apple and potato crop protection show three potential functions: DISCUSS can be used as (1) a simulation tool for communication and decision support, (2) an assessment and monitoring tool, and (3) a discussion support tool for farmer groups. Analysis of these functionalities using a framework for guiding on-farm sustainability assessment and strategic decision-making shows how each functionality can support the consecutive steps of transition to SCP, i.e. using the right tool functionality at the right time. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Protective effect study of polysaccharides from tremella fuciformis on hematopoietic function in radiation-injured mice

    Xu Wenqing; Chinese Academy of Medical Sciences, Tianjin; Gao Wenyuan; Shen Xiu; Wang Yueying; Liu Peixun

    2006-01-01

    Objective: To study the protective effects of polysaccharides of Tremella fuciformis on hematopoietic function in radiation-injured mice. Methods; Colony-forming unit of spleen (CFU-S), number of nucleated cells in bone marrow (BMNC) and spleen index were used to investigated the effect of polysacharides from tremella fuciformis at 6 mg/kg, 12 mg/kg, 24 mg/kg on hematopoietic function of mice irradiated with 7.5 Gy 137 Cs γ-rays. Results: On the 9 the day after irradiation compared with the negative control group number of nucleated cells in bone marrow, colony-forming unit of spleen and spleen index of mice have treated with polysaccharides from Tremella fuciformis intraperitoneally for three days prior to irradiation increased markedly. Conclusion: Polysaccharides of tremella fuciformis have protective effect on hematopoietic function of radiation-injured mice. (authors)

  17. Mumps Parotitis and Ovarian Cancer: Modern Significance of an Historic Association

    2009-10-01

    ligation or a breast mastitis , found to protect against ovarian cancer, might do so by causing overexpression of the hypoglycosylated form of MUC1...negative plates were incubated overnight and washed three times with PBS before addition of 100 μl of 2.5% bovine serum albumin in PBS. Serially...a breast mastitis which have been shown to protect against ovarian cancer(10), might confer protection because of injury to the tissue causing

  18. Mathematical verification of a nuclear power plant protection system function with combined CPN and PVS

    Koo, Seo Ryong; Son, Han Seong; Seong, Poong Hyun [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1999-12-31

    In this work, an automatic software verification method for Nuclear Power Plant (NPP) protection system is developed. This method utilizes Colored Petri Net (CPN) for modeling and Prototype Verification System (PVS) for mathematical verification. In order to help flow-through from modeling by CPN to mathematical proof by PVS, a translator has been developed in this work. The combined method has been applied to a protection system function of Wolsong NPP SDS2(Steam Generator Low Level Trip) and found to be promising for further research and applications. 7 refs., 10 figs. (Author)

  19. Mathematical verification of a nuclear power plant protection system function with combined CPN and PVS

    Koo, Seo Ryong; Son, Han Seong; Seong, Poong Hyun [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1998-12-31

    In this work, an automatic software verification method for Nuclear Power Plant (NPP) protection system is developed. This method utilizes Colored Petri Net (CPN) for modeling and Prototype Verification System (PVS) for mathematical verification. In order to help flow-through from modeling by CPN to mathematical proof by PVS, a translator has been developed in this work. The combined method has been applied to a protection system function of Wolsong NPP SDS2(Steam Generator Low Level Trip) and found to be promising for further research and applications. 7 refs., 10 figs. (Author)

  20. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

    Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

    2013-06-01

    The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

  1. Ovarian tubercular abscess mimicking ovarian carcinoma: A rare case report

    Abinash Agarwala

    2015-01-01

    Full Text Available Although genito-urinary tuberculosis is common, reports of isolated ovarian tubercular abscess are rare. Ovarian tubercular abscess may mimics that of an ovarian tumor, leading to diagnostic difficulties. We reported a case report of 35 years woman presented with chronic pain abdomen, weight loss, low-grade fever and a right ovarian mass on ultrasound, with a significantly elevated CA-125 level. On clinical and radiological evidence, diagnosis of ovarian carcinoma was made, and laparotomy was performed with resection of the ovary. Postoperative specimen sent for histological examination that revealed classic epithelioid granuloma and acid-fast bacilli were present in Ziehl-Neelsen stain. Patient was put on antitubercular regimen from our Dots center. She is improving clinical after taking antitubercular drug and is on regular follow up at our chest outpatient department. Ovarian tubercular abscess is common in young women living in endemic zones, but case report of isolated tubercular abscess is rarely reported. CA-125 can be raised in both ovarian tubercular abscess and ovarian carcinoma, and only imaging is not always conclusive. Laparotomy followed by tissue diagnosis can be helpful in this situation. As the prognosis and treatment outcome of ovarian tubercular abscess and ovarian carcinoma is different, proper diagnosis by laparotomy should be done. Early diagnosis of ovarian tubercular abscess is vital as untreated disease can lead to infertility.

  2. Differential hRad17 expression by histologic subtype of ovarian cancer

    Young Jennifer L

    2011-03-01

    Full Text Available Abstract Background In the search for unique ovarian cancer biomarkers, ovarian specific cDNA microarray analysis identified hRad17, a cell cycle checkpoint protein, as over-expressed in ovarian cancer. The aim of this study was to validate this expression. Methods Immunohistochemistry was performed on 72 serous, 19 endometrioid, 10 clear cell, and 6 mucinous ovarian cancers, 9 benign ovarian tumors, and 6 normal ovarian tissue sections using an anti-hRad17 antibody. Western blot analysis and quantitative PCR were performed using cell lysates and total RNA prepared from 17 ovarian cancer cell lines and 6 normal ovarian epithelial cell cultures (HOSE. Results Antibody staining confirmed upregulation of hRad17 in 49.5% of ovarian cancer cases. Immunohistochemistry demonstrated that only 42% of serous and 47% of endometrioid subtypes showed overexpression compared to 80% of clear cell and 100% of mucinous cancers. Western blot confirmed overexpression of hRad17 in cancer cell lines compared to HOSE. Quantitative PCR demonstrated an upregulation of hRad17 RNA by 1.5-7 fold. hRad17 RNA expression differed by subtype. Conclusions hRad17 is over-expressed in ovarian cancer. This over-expression varies by subtype suggesting a role in the pathogenesis of these types. Functional studies are needed to determine the potential role of this protein in ovarian cancer.

  3. Genetic investigation into ethnic disparity in polycystic ovarian syndrome

    Li, Shuxia; Zhu, Dongyi; Duan, Hongmei

    2013-01-01

    Polycystic ovarian syndrome is universally the most common endocrinopathy in women of reproductive age. It is characterized by composite clinical phenotypes reflecting the reproductive impact of ovarian dysfunction (androgen excess, oligo-/anovulation, polycystic ovary) and metabolic abnormalities...... more efficient strategies for treatment and prevention of polycystic ovarian syndrome....... to unravel the molecular basis of the interethnic difference in the pathogenesis of the syndrome. It is hoped that identification and characterization of population-specific structural genetic and functional genomic patterns could help to not only deepen our understanding of the aetiology but also develop...

  4. Premature ovarian insufficiency: Pathogenesis and management

    Anna J Fenton

    2015-01-01

    Full Text Available The term premature ovarian insufficiency (POI describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI.

  5. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

    Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

    2015-01-01

    Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic

  6. Exercise protects from cancer through regulation of immune function and inflammation

    Hojman, Pernille

    2017-01-01

    Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are...... regulation of immune and inflammatory functions, and exercise may be pursued as anticancer treatment through incorporation into standard oncological therapy to the benefit of the cancer patients.......Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection...... are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Here, I review the role of exercise in protection from...

  7. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Kover, Karen, E-mail: kkover@cmh.edu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  8. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-01-01

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H 2 O 2 assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H 2 O 2 levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP

  9. Ovarian cancer surgery

    Seibaek, Lene; Blaakaer, Jan; Petersen, Lone Kjeld

    2013-01-01

    PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... standard levels. Concerning mental health, levels were below standard during the entire period, but did improve with time, also in women in whom the potential cancer diagnosis was refuted. The preoperative differences between these groups leveled out postoperatively in terms of physical health. At the end...

  10. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

    2017-02-01

    Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  11. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Nidhi Jain

    2017-02-01

    Full Text Available Following Japanese encephalitis virus (JEV infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null are highly susceptible and die over 10-18 day period as compared to the wild-type (WT mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB. Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  12. Endogenous ovarian hormones affect mitochondrial efficiency in cerebral endothelium via distinct regulation of PGC-1 isoforms.

    Kemper, Martin F; Zhao, Yuanzi; Duckles, Sue P; Krause, Diana N

    2013-01-01

    Mitochondria support the energy-intensive functions of brain endothelium but also produce damaging-free radicals that lead to disease. Previously, we found that estrogen treatment protects cerebrovascular mitochondria, increasing capacity for ATP production while decreasing reactive oxygen species (ROS). To determine whether these effects occur specifically in endothelium in vivo and also explore underlying transcriptional mechanisms, we studied freshly isolated brain endothelial preparations from intact and ovariectomized female mice. This preparation reflects physiologic influences of circulating hormones, hemodynamic forces, and cell-cell interactions of the neurovascular unit. Loss of ovarian hormones affected endothelial expression of the key mitochondrial regulator family, peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), but in a unique way. Ovariectomy increased endothelial PGC-1α mRNA but decreased PGC-1β mRNA. The change in PGC-1β correlated with decreased mRNA for crucial downstream mitochondrial regulators, nuclear respiratory factor 1 and mitochondrial transcription factor A, as well as for ATP synthase and ROS protection enzymes, glutamate-cysteine ligase and manganese superoxide dismutase. Ovariectomy also decreased mitochondrial biogenesis (mitochondrial/nuclear DNA ratio). These results indicate ovarian hormones normally act through a distinctive regulatory pathway involving PGC-1β to support cerebral endothelial mitochondrial content and guide mitochondrial function to favor ATP coupling and ROS protection.

  13. Impact Analysis of Electrical Current Characteristics in Relay Function for Electrical and Electronic Protection

    Syirrazie Che Soh; Harzawadi Hasim

    2013-01-01

    This paper is to study effect of electrical current on relay reaction, which has coil and switch inside the relay. An analysis on the electrical current will be conducted to determine current limitation for relay activation purpose. The result of analysis showing that current characteristic of relay and applied load will present their affect to the relay function performance. Finding from this result will bring the idea to develop a suitable design circuit for electrical and electronic protection. (author)

  14. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation.

    Ling-Yun Chu

    Full Text Available The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK.

  15. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.

    Flannick, Jason; Thorleifsson, Gudmar; Beer, Nicola L; Jacobs, Suzanne B R; Grarup, Niels; Burtt, Noël P; Mahajan, Anubha; Fuchsberger, Christian; Atzmon, Gil; Benediktsson, Rafn; Blangero, John; Bowden, Don W; Brandslund, Ivan; Brosnan, Julia; Burslem, Frank; Chambers, John; Cho, Yoon Shin; Christensen, Cramer; Douglas, Desirée A; Duggirala, Ravindranath; Dymek, Zachary; Farjoun, Yossi; Fennell, Timothy; Fontanillas, Pierre; Forsén, Tom; Gabriel, Stacey; Glaser, Benjamin; Gudbjartsson, Daniel F; Hanis, Craig; Hansen, Torben; Hreidarsson, Astradur B; Hveem, Kristian; Ingelsson, Erik; Isomaa, Bo; Johansson, Stefan; Jørgensen, Torben; Jørgensen, Marit Eika; Kathiresan, Sekar; Kong, Augustine; Kooner, Jaspal; Kravic, Jasmina; Laakso, Markku; Lee, Jong-Young; Lind, Lars; Lindgren, Cecilia M; Linneberg, Allan; Masson, Gisli; Meitinger, Thomas; Mohlke, Karen L; Molven, Anders; Morris, Andrew P; Potluri, Shobha; Rauramaa, Rainer; Ribel-Madsen, Rasmus; Richard, Ann-Marie; Rolph, Tim; Salomaa, Veikko; Segrè, Ayellet V; Skärstrand, Hanna; Steinthorsdottir, Valgerdur; Stringham, Heather M; Sulem, Patrick; Tai, E Shyong; Teo, Yik Ying; Teslovich, Tanya; Thorsteinsdottir, Unnur; Trimmer, Jeff K; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Vaziri-Sani, Fariba; Voight, Benjamin F; Wilson, James G; Boehnke, Michael; McCarthy, Mark I; Njølstad, Pål R; Pedersen, Oluf; Groop, Leif; Cox, David R; Stefansson, Kari; Altshuler, David

    2014-04-01

    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.

  16. INFLUENCE OF PETROCHEMICAL INDUSTRY ENVIRONMENTAL CONTAMINANTS ON ANIMAL OVARIAN CELLS

    Alexander V. Sirotkin

    2012-10-01

    Full Text Available The aim of our studies was to examine (1 the effect of environmental contaminants (benzene, toluene and xylen on basic ovarian cell functions (proliferation, apoptosis, secretory activity in different animal species (rabbit, pig, cow, and (2 whether gonadotropic hormone (FSH and plant molecules (quercetin, resveratrol or extract of yucca can affect these functions and modify effect of environmental contaminants. It was observed, that the culture of either porcine or bovine ovarian cells with benzene, toluene or xylen promote apoptosis (accumulation of apoptosis markers bax and p53 and proliferation (accumulation of PCNA. Furthermore, additions of these contaminants were able either up- or down-regulate the release of progesterone, oxytocin, insulin-like growth factor I (IGF-I and prostaglandin F by cultured porcine, rabbit and bovine ovarian cells and their response to addition of FSH. FSH additions promoted proliferation, apoptosis and release of molecules listed above by porcine granulosa cells. Moreover, FSH was able to modify and to prevent. Some effects of BTEX on these cells. The effects of either quercetin or resveratrol on basic porcine ovarian cell functions were observed, but these plant molecules were not able to prevent BTEX effect. Feeding of rabbits with yucca extract caused changes in release of progesterone, IGF-I and prostaglandin F by their ovarian cells, as well as to modify and prevent the influence of benzene on ovarian hormone release. The obtained data suggest that (1 the negative effect of BTEX on reproduction can be due to their influence on ovarian cell apoptosis, proliferation, turnover and release of peptide and steroid hormones and growth factors, and that (2 FSH and plant molecules can regulate ovarian cell functions and prevent some effects of BTEX on these cells.

  17. Premature ovarian failure

    Pacheco, José

    2011-01-01

    Premature ovarian failure is characterized by secondary amenorrhea affecting a woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberratio...

  18. Polycystic ovarian syndrome

    Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

  19. Ovarian chocolate cysts

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kitagaki, Hajime; Tanaka, Yutaka; Yamasaki, Katsuhito; Shimizu, Tadafumi; Kono, Michio.

    1988-01-01

    Accurate preoperative staging of ovarian chocolate cysts is very important because recent hormonal therapy has been effective in low stage patients. However, it has been difficult to assess the preoperative stage of ovarian chocolate cysts. We evaluated the diagnostic potential of MRI in preoperative staging of 15 overian chocolate cysts. It was well known that the older the ovarian chocolate cyst was the more iron content it had. We examined the iron contents effect on T1 and T2 relaxation times in surgically confirmed chocolate cysts (stage II: 3 cases, stage III: 3 cases and stage IV: 9 cases by AFS classification, 1985) employing the 0.15-T MR system and 200 MHz spectrometer. There was a positive linear relation between T1 of the lesion using the MR system (T1) and T1 of the resected contents using the spectrometer (sp-T1); r = 0.93. The same relation was revealed between T2 and sp-T2; r = 0.87. It was indicated that T1 and T2 using the MR system was accurate. There was a negative linear relation between T1 and the iron contents ( r = -0.81) but no relation between T2 and the iron contents. T1 was 412 ± 91 msec for stage II, 356 ± 126 msec for stage III and 208 ± 30 msec for stage IV. T1 for stage IV was shorter than that for stage II and III, statistically significant differences were noted (p < 0.05). Thus, T1 was useful in differentiating a fresh from an old ovarian chocolate cyst. We concluded that T1 relaxation time using the MR system was useful for the staging of an ovarian chocolate cyst without surgery. (author)

  20. [The so-called "chocolate cyst"--frequently misinterpreted as ovarian endometriosis?].

    Christensen, B; Schindler, A E

    1996-09-01

    Limitation of morphological diagnostic and possible misinterpretations are shown in a patient with anamnestic ovarian endometriosis. In cases of "chocolate cysts" it is necessary to differentiate between ovarian endometriosis and functional cysts. Hints for the existence of a functional cyst are an atypical past history or perioperative findings. Biochemical analysis of the cyst fluid may lead to a correct diagnosis.

  1. Risk assessment of salinity and turbidity in Victoria (Australia) to stream insects' community structure does not always protect functional traits.

    Kefford, Ben J; Schäfer, Ralf B; Metzeling, Leon

    2012-01-15

    Ecological risk assessments mostly consider measures of community composition (structure) across large spatial scales. These assessments, using species sensitivity distributions (SSDs) or the relative species retention (RSR), may not be protective of ecosystem functions and services at smaller spatial scales. Here we examine how changes in biological traits, as proxy for ecosystem functions/services, at a fine spatial scale relate to larger scale assessment of structure. We use functional traits of stream insect species in south-east Australia in two habitats (riffle and edge/pool). We find that the protection of community structure in terms of 95% of species over multiple sites against adverse effects of salinity (as electrical conductivity) and turbidity will mostly, but not always, protect traits at smaller scales. Considering different combinations of trait modalities, contaminants and habitat, a mean of 17.5% (range 0%-36.8) of cases would result in under-protection of trait modalities despite protecting species composition (in terms of Jaccard's Index). This under-protection of trait modalities is only because of the different spatial scales that community structure and the traits were considered. We recommend that where the protection of biological traits, ecosystem functions or ecosystem services from stressors is a management goal, protective targets should not be solely set using measures of community structure such as SSDs or RSR. To protect both structural and functional attributes separate risk assessments should be done. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion.

    Cooke, Niamh M

    2015-09-09

    Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level.

  3. Thiolated silicone oils as adhesive skin protectants for improved barrier function.

    Partenhauser, A; Zupančič, O; Rohrer, J; Bonengel, S; Bernkop-Schnürch, A

    2016-06-01

    The purpose of this study was the evaluation of thiolated silicone oil as novel skin protectant exhibiting prolonged residence time, enhanced barrier function and reinforced occlusivity. Two silicone conjugates were synthesized with mercaptopropionic acid (MPA) and thioglycolic acid (TGA) as thiol ligands. Adhesion, protection against artificial urine and water vapour permeability with both a Payne cup set-up and transepidermal water loss (TEWL) measurements on porcine skin were assessed. Silicone thiomers showed pronounced substantivity on skin with 22.1 ± 6.3% and 39.2 ± 6.7% remaining silicone after 8 h for silicone-TGA and silicone-MPA, respectively, whereas unmodified silicone oil and dimethicone were no longer detectable. In particular, silicone-MPA provided a protective shield against artificial urine penetration with less than 25% leakage within 6 h. An up to 2.5-fold improved water vapour impermeability for silicone-MPA in comparison with unmodified control was discovered with the Payne cup model. In addition, for silicone-MPA a reduced TEWL by two-thirds corresponding to non-thiolated control was determined for up to 8 h. Thiolation of silicone oil leads to enhanced skin adhesiveness and barrier function, which is a major advantage compared to commonly used silicones and might thus be a promising treatment modality for various topical applications. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  4. A Theoretical Analysis: Physical Unclonable Functions and The Software Protection Problem

    Nithyanand, Rishab [Stony Brook Univ., NY (United States); Solis, John H. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2011-09-01

    Physical Unclonable Functions (PUFs) or Physical One Way Functions (P-OWFs) are physical systems whose responses to input stimuli (i.e., challenges) are easy to measure (within reasonable error bounds) but hard to clone. This property of unclonability is due to the accepted hardness of replicating the multitude of uncontrollable manufacturing characteristics and makes PUFs useful in solving problems such as device authentication, software protection, licensing, and certified execution. In this paper, we focus on the effectiveness of PUFs for software protection and show that traditional non-computational (black-box) PUFs cannot solve the problem against real world adversaries in offline settings. Our contributions are the following: We provide two real world adversary models (weak and strong variants) and present definitions for security against the adversaries. We continue by proposing schemes secure against the weak adversary and show that no scheme is secure against a strong adversary without the use of trusted hardware. Finally, we present a protection scheme secure against strong adversaries based on trusted hardware.

  5. Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess: a causative link to polycystic ovarian syndrome.

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-10-24

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.

  6. Performance Improvement of the Core Protection Calculator System (CPCS) by Introducing Optimal Function Sets

    Won, Byung Hee; Kim, Kyung O; Kim, Jong Kyung; Kim, Soon Young

    2012-01-01

    The Core Protection Calculator System (CPCS) is an automated device which is adopted to inspect the safety parameters such as Departure from Nuclear Boiling Ratio (DNBR) and Local Power Density (LPD) during normal operation. One function of the CPCS is to predict the axial power distributions using function sets in cubic spline method. Another function of that is to impose penalty when the estimated distribution by the spline method disagrees with embedded data in CPCS (i.e., over 8%). In conventional CPCS, restricted function sets are used to synthesize axial power shape, whereby it occasionally can draw a disagreement between synthesized data and the embedded data. For this reason, the study on improvement for power distributions synthesis in CPCS has been conducted in many countries. In this study, many function sets (more than 18,000 types) differing from the conventional ones were evaluated in each power shape. Matlab code was used for calculating/arranging the numerous cases of function sets. Their synthesis performance was also evaluated through error between conventional data and consequences calculated by new function sets

  7. Targeting FR-expressing cells in ovarian cancer with Fab-functionalized nanoparticles: a full study to provide the proof of principle from in vitro to in vivo.

    Quarta, Alessandra; Bernareggi, Davide; Benigni, Fabio; Luison, Elena; Nano, Giuseppe; Nitti, Simone; Cesta, Maria Candida; Di Ciccio, Luciano; Canevari, Silvana; Pellegrino, Teresa; Figini, Mariangela

    2015-02-14

    Efficient targeting in tumor therapies is still an open issue: systemic biodistribution and poor specific accumulation of drugs weaken efficacy of treatments. Engineered nanoparticles are expected to bring benefits by allowing specific delivery of drug to the tumor or acting themselves as localized therapeutic agents. In this study we have targeted epithelial ovarian cancer with inorganic nanoparticles conjugated to a human antibody fragment against the folate receptor over-expressed on cancer cells. The conjugation approach is generally applicable. Indeed several types of nanoparticles (either magnetic or fluorescent) were engineered with the fragment, and their biological activity was preserved as demonstrated by biochemical methods in vitro. In vivo studies with mice bearing orthotopic and subcutaneous tumors were performed. Elemental and histological analyses showed that the conjugated magnetic nanoparticles accumulated specifically and were retained at tumor sites longer than the non-conjugated nanoparticles.

  8. Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment.

    Manikkam, Mohan; Steckler, Teresa L; Welch, Kathleen B; Inskeep, E Keith; Padmanabhan, Vasantha

    2006-04-01

    Prenatal testosterone (T) excess during midgestation leads to estrous cycle defects and polycystic ovaries in sheep. We hypothesized that follicular persistence causes polycystic ovaries and that cyclic progesterone (P) treatment would overcome follicular persistence and restore cyclicity. Twice-weekly blood samples for P measurements were taken from control (C; n = 16) and prenatally T-treated (T60; n = 14; 100 mg T, im, twice weekly from d 30-90 of gestation) Suffolk sheep starting before the onset of puberty and continuing through the second breeding season. A subset of C and T60 sheep were treated cyclically with a modified controlled internal drug-releasing device for 13-14 d every 17 d during the first anestrus (CP, 7; TP, 6). Transrectal ovarian ultrasonography was performed for 8 d in the first and 21 d in the second breeding season. Prenatal T excess reduced the number, but increased the duration of progestogenic cycles, reduced the proportion of ewes with normal cycles, increased the proportion of ewes with subluteal cycles, decreased the proportion of ewes with ovulatory cycles, induced the occurrence of persistent follicles, and reduced the number of corpora lutea in those that cycled. Cyclic P treatment in anestrus, which produced one third the P concentration seen during luteal phase of cycle, did not reduce the number of persistent follicles, but increased the number of progestogenic cycles while reducing their duration. These findings suggested that follicular persistence might contribute to the polycystic ovarian morphology. Cyclic P treatment was able to only partially restore follicular dynamics, but this may be related to the low replacement concentrations of P achieved.

  9. Protective effects of simvastatin on coronary artery function in swine with acute infection

    Liuba, Petru; Pesonen, Erkki; Forslid, Anders

    2006-01-01

    cholesterol) between the groups (p>0.2). CONCLUSION:: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering......BACKGROUND:: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. METHODS......:: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneumoniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pre-treated with simvastatin (80mg daily), while...

  10. TRPM7 is required for ovarian cancer cell growth, migration and invasion

    Wang, Jing; Liao, Qian-jin [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Yi [Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410078 (China); Zhou, Hui; Luo, Chen-hui; Tang, Jie; Wang, Ying; Tang, Yan; Zhao, Min; Zhao, Xue-heng [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Qiong-yu [Department of Basic Medical Science, Yongzhou Vocational Technical College, Yong Zhou 425100 (China); Xiao, Ling, E-mail: lingxiaocsu@126.com [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013 (China); Institute of Clinical Pharmacology, Central South University, Changsha 410018 (China)

    2014-11-28

    Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

  11. Self-protective function of post-conflict bystander affiliation in mandrills.

    Gabriele Schino

    Full Text Available BACKGROUND: Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. METHODOLOGY/PRINCIPAL FINDINGS: We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx. We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim's distress (as measured by its scratching rates and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. CONCLUSIONS/SIGNIFICANCE: These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses.

  12. Concepts on integration of physical protection and material accounting functions in a safeguards system

    Reynolds, D.A.

    1981-01-01

    Concepts on integration of physical protection and material accounting systems to enhance overall safeguards capability are developed and presented. Integration is approached by coordinating all safeguards information through a safeguards coordination center. This center represents a higher level in a communication, data-processing, and decision-making structure which is needed for efficient real-time operation of the integrated system. The safeguards coordination center functions to assess alarm and warning data required to resolve threats in the safeguards system, coordinate information and interaction involving the material accounting, physical protection, and facility monitoring and control systems, and present a single unified interface for interaction with facility management, facility operations, safeguards system personnel, and response forces

  13. Protection and safety functions of different off-gas treatment systems in radioactive waste incineration

    Caramelle, D.; Chevalier, G.; Chevalier, G.

    1986-01-01

    Gaseous effluent cleaning installations are designed to protect workmen and environment and must be efficient enough to guarantee that the amounts of gases and dusts emitted by a furnace operating normally or accidentally are at an acceptable level in the atmosphere on the incinerator site. The process equipments necessary to operations and the monitoring devices must be reliable. The main risk in normal operation is occupational exposure close to the radioactive products accumulation points. The accidental risks are mainly related to an outage of the off-gas cleaning or a tightness failure with radioactive products dissemination resulting from either internal perturbation (filter tear, exhauster failure, ...) or external incident (electricity cut-off, furnace disarrangements, fire or explosion inside the incinerator). In view of these risks, it is interesting to examine the safety and protection functions of different components of off-gas treatment systems

  14. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

    Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

    2009-07-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.

  15. Protective effect of dexmedetomidine combined with ulinastatin on cardiopulmonary function injury caused by cardiopulmonary bypass surgery

    Zhu Zhu

    2016-11-01

    Full Text Available Objective: To analyze the protective effect of dexmedetomidine combined with ulinastatin on cardiopulmonary function impairment caused by cardiopulmonary bypass surgery. Methods: A total of 78 patients who received valve replacement under cardiopulmonary bypass were divided into observation group and control group (n=39 according to random number table. Control group received intraoperative ulinastatin intervention and observation group received intraoperative dexmedetomidine combined with ulinastatin intervention. Differences in the levels of cardiac function indexes, myocardial injury markers, pulmonary function parameters, inflammatory indexes and so on were compared between two groups of patients 24 hours after operation. Results: Cardiac function parameters LSV, RSV and RVEF values of observation group 24 hours after operation were higher than those of control group while PAP value was lower than that of control group; serum myocardial injury markers H-FABP, cTn-T, CKMB, cTnⅠ and NT-proBNP levels were lower than those of control group; lung function parameters Cs and Cd values were higher than those of control group while RI, R5-R20, X5 and Fres values were lower than those of control group; serum pro-inflammatory factors IL-6 and TNF-α levels were lower than those of control group while anti-inflammatory factors sTNF-RI, IL-4 and IL-10 levels were higher than those of control group. Conclusions: Dexmedetomidine combined with ulinastatin can protect the cardiopulmonary function in patients with cardiopulmonary bypass, and help to reduce the occurrence of postoperative cardiopulmonary dysfunction and other severe complications.

  16. Cryopreservation of canine ovarian and testicular fibroblasts.

    Yu, Il-Jeoung; Leibo, S P; Songsasen, Nucharin; Dresser, Betsy L; Kim, In-Shik

    2009-01-01

    To derive a practical procedure to store canine somatic cells, fibroblasts isolated from testicular or ovarian tissues were cryopreserved in 1.2 M ethylene glycol or in 1.2 M dimethylsulfoxide prepared in Dulbecco's Modified Eagle Medium as cryoprotectants, and were frozen either in plastic straws or vials. Thawed cells were cultured for 24 hr at 38.5 degree C in a humidified atmosphere of 5 percent CO2 95 percent air, and then their membrane integrity was assayed with a double fluorescent stain, Fertilight. In addition, frozen-thawed fibroblasts were cultured for 4 days, and then their functional survival was measured after staining small colonies with trypan blue. After freezing and thawing, membrane integrity of testicular fibroblasts was 55-70 percent and functional survival ranged from 20-40 percent. With frozen-thawed ovarian cells, the average membrane integrity was 55-75 percent and the average functional survival was 35-40 percent. When frozen in ethylene glycol, functional survival of ovarian fibroblasts was significantly higher than that of testicular cells (P less than 0.05). These methods should prove useful to preserve cells collected from canids in the wild.

  17. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Patricia Fernandez

    2014-10-01

    Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

  18. Form and Function in Doing Business Rankings: is Investor Protection in Italy Still so Bad?

    Luca Enriques

    2016-07-01

    Full Text Available The World Bank’s Doing Business Report (DBR ranks every year numerous jurisdictions across the globe according to their ability to facilitate business activities. Among the indexes contributing to the definition of the global competitiveness of the legislations, the “Protecting investors index” (PII measures the protection of minority shareholders in listed companies. In this paper, we analyse the DBR’s assessment of the Italian regulatory framework on investor protection. We find that the PII falls short of properly evaluating the applicable rules. First, it underrates Italy because the DBR evaluation falls short of properly evaluating the role performed by independent directors under Italian rules on related party transactions. In particular, the DBR fails to properly account for independent directors’ power to veto unfair transactions before they are submitted to the board, a safeguard that ensures minority investors’ protection at least as well as mandatory abstention by conflicted directors. Second, past DBR overrated the PII, so that subsequent reforms that substantially improved investor protection have not been grasped by more recent assessments, giving the misleading impression that no relevant changes have occurred. Far from representing one of the multiple coding errors reported in the literature, these flaws aptly show that the DBR methodology, while correctly attempting to preserve consistency in the evaluation of different jurisdictions, adopts an excessively formalistic approach and disregards the function of the rules it scrutinizes. In light of the influence that the DBR exerts on national policymakers, this approach is detrimental because it might induce window-dressing reforms. Moreover, it may rule out experimentation, which is key to ensuring that the applicable rules keep pace with the variety of techniques adopted to expropriate minority shareholders.

  19. Distinct functions for the Drosophila piRNA pathway in genome maintenance and telomere protection.

    Jaspreet S Khurana

    2010-12-01

    Full Text Available Transposons and other selfish DNA elements can be found in all phyla, and mobilization of these elements can compromise genome integrity. The piRNA (PIWI-interacting RNA pathway silences transposons in the germline, but it is unclear if this pathway has additional functions during development. Here we show that mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead to extensive fragmentation of the zygotic genome during the cleavage stage of embryonic divisions. Additionally, aub and armi show defects in telomere resolution during meiosis and the cleavage divisions; and mutations in lig-IV, which disrupt non-homologous end joining, suppress these fusions. By contrast, lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation studies show that aub and armi mutations disrupt telomere binding of HOAP, which is a component of the telomere protection complex, and reduce expression of a subpopulation of 19- to 22-nt telomere-specific piRNAs. Mutations in rhi and ago3, by contrast, do not block HOAP binding or production of these piRNAs. These findings uncover genetically separable functions for the Drosophila piRNA pathway. The aub, armi, rhi, and ago3 genes silence transposons and maintain chromosome integrity during cleavage-stage embryonic divisions. However, the aub and armi genes have an additional function in assembly of the telomere protection complex.

  20. Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model

    Jae-Hwan Lee

    2017-02-01

    Full Text Available Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells. The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg, was used to induce premature ovarian failure (POF. Methylparaben (MP, 100 mg/kg, propylparaben (PP, 100 mg/kg, and butylparaben (BP, 100 mg/kg dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh. All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.

  1. Possible impacts of forest decline on the protection functions of forests in the Bavarian Alps

    Suda, M

    1989-01-01

    In context with the forest decline phenomenon the question arises on how the protection function of forests will be affected and how possible impacts can be evaluated. First, a solution model based on a feedback-circle system is presented, which allows to assess possible impacts of forest decline on massmovements. The application of this approach to the avalanche and flooding phenomena is presented and demonstrated by model calculations for different examples in the country of Traunstein/Bavaria Alps. Finally, a model is presented which gives an answer to the question, what impacts on the tourism industry are possible due to forest decline and how these influences can be evaluated.

  2. The functionalities of the Darwin radioactivity calculation form and the radiation protection studies

    Tsilanizara, A.; Huynh, T.D.; Luneville, L.; Diop, C.M.; Eid, M.

    2003-01-01

    The characterisation of the radioactive sources relative to the evolution of nuclear fuels or to the activation under particles flux (generally neutrons) of structures of a nuclear equipment or a simple isotope decay is a step in the radiation protection studies. This characterisation needs to know a fundamental knowledge: the radionuclides concentration. This one changes with time, and follows the coupled differential equations of first order in time, the generalised Bateman equations. The objective of this paper is to present the functionalities of the Darwin form, developed by the Cea and dedicated to the study of radioactivity. (N.C.)

  3. Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis.

    Khodaverdi, Sepideh; Nazari, Leila; Mehdizadeh-Kashi, Abolfazl; Vahdat, Mansoureh; Rokhgireh, Samaneh; Farbod, Ali; Tajbakhsh, Banafsheh

    2018-04-01

    Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs) and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests. Copyright© by Royan Institute. All rights reserved.

  4. Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis

    Sepideh Khodaverdi

    2018-01-01

    Full Text Available Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS, a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests.

  5. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  6. Tubo-ovarian actinomycosis.

    Shroff C

    1981-01-01

    Full Text Available Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 months earlier. The 2nd case sought medical attention for backache and leucorrhea of 4 years′ duration. Exploratory laparotomy in the 1st case revealed tubo-ovarian masses; the vermiform appendix was not traceable. The uterine cavity in the 2nd case harbored a wooden stick. Direct extension from established ileocacal actinomycosis was believed to involve the female genital adnexae in the past. Association of tubo-ovarian actinomycosis with the presence of a foreign body in the female genital tract has been reported sporadically in the literature, yet an increase in the incidence may be expected because of the frequent use of intrauterine contraceptive devices in recent times. It is suggested that in women presenting clinically with vague abdominal symptoms, backache and discharge, actinomycosis should be considered and ruled out with the help of cytologic and proper microbial culture methods. Once the diagnosis is established, the infection can be treated with good results with penicillin.

  7. Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

    2018-06-04

    Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

  8. Are Protected Areas Required to Maintain Functional Diversity in Human-Modified Landscapes?

    Cottee-Jones, H. Eden W.; Matthews, Thomas J.; Bregman, Tom P.; Barua, Maan; Tamuly, Jatin; Whittaker, Robert J.

    2015-01-01

    The conversion of forest to agriculture across the world’s tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities. PMID:25946032

  9. Improved design architecture to minimize functional complexity of plant protection system for nuclear power plant

    Jung, JaeCheon

    2016-01-01

    An improved design architecture method to minimize the functional complexity of PPS (Plant Protection System) is proposed in this work. Firstly, the design concerns are identified with both AHP (Analytic Hierarchy Process) analysis. AHP is able to identify the source of design concerns using pairwise comparison. AHP result shows CCF is the primary concern and the complexity is the secondly. Even though complexity is the second largest concern to the effectiveness of digital I&C system, but it has not been highlighted as CCF. This is the reason why this work focuses on the sources of complexity to maximize the effectiveness of digital system in the viewpoint of design architecture. The proposed methods are, separating non-safety functions from bistable logics and simplifying communication links and network. In order to verify the new concept, EFFBD (Enhanced Functional Flow Block Diagram) models are developed for two bistable logics of PPS and the complexities are measured using Halstead’s program maintainability measures. This measure specifies what provokes functional complexity. Periodic testing and operating bypass function are the source of complexity in this analysis.

  10. Improved design architecture to minimize functional complexity of plant protection system for nuclear power plant

    Jung, JaeCheon, E-mail: jcjung@kings.ac.kr

    2016-12-01

    An improved design architecture method to minimize the functional complexity of PPS (Plant Protection System) is proposed in this work. Firstly, the design concerns are identified with both AHP (Analytic Hierarchy Process) analysis. AHP is able to identify the source of design concerns using pairwise comparison. AHP result shows CCF is the primary concern and the complexity is the secondly. Even though complexity is the second largest concern to the effectiveness of digital I&C system, but it has not been highlighted as CCF. This is the reason why this work focuses on the sources of complexity to maximize the effectiveness of digital system in the viewpoint of design architecture. The proposed methods are, separating non-safety functions from bistable logics and simplifying communication links and network. In order to verify the new concept, EFFBD (Enhanced Functional Flow Block Diagram) models are developed for two bistable logics of PPS and the complexities are measured using Halstead’s program maintainability measures. This measure specifies what provokes functional complexity. Periodic testing and operating bypass function are the source of complexity in this analysis.

  11. Enhancing the functionality of reactor protection systems to provide diagnostic and monitoring information: The ISATTM approach

    Baldwin, J.A.; Rowe, B.J.; Jones, C.D.

    1996-01-01

    The ISAT TM architecture has been successfully implemented as the Single Channel Trip System (SCTS), part of the primary protection system of Nuclear Electric's Dungeness 'B' Advanced Gas-Cooled Reactors. The system is the first computer-based protection system licensed on a UK civil nuclear reactor. The system provides protection against single channel faults resulting in high coolant gas outlet temperature. The SCTS was designed to output data at several points in the system to an Ethernet to allow checks to be made on the operation of parts of the protection system and the system as a whole. In order to monitor the performance of this shutdown system a PC based monitoring system was developed to take input as data from the Ethernet, check its integrity and then analyze the data to provide information of the state of the system and subsystems. The SCTS monitor was basically intended to alert the operator to any fault on the safety system and indicate its source, provide a diagnosis of the cause of any trip initiated by the safety system, and log the occurrences of these incidents for later inspection. The intention was also to provide accurate real-time information on the thermocouple readings and to decrease the effort required to maintain the safety system. This paper will describe briefly the development of the ISAT TM monitoring system: how its requirements were arrived at, and how the design, code and testing were carried out to ensure approval for this application. It will then go on to report how the ISAT TM monitor has performed during its time in service: how more functionality has been added over and above its original requirements. Features of additional monitors for the SCTS and other ISAT TM systems will also be described. (author). 2 refs, 5 figs

  12. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Mathematical verification of a nuclear power plant protection system function with combined CPN and PVS

    Koo, Seo Ryong; Son, Han Seong; Seong, Poong Hyun

    1999-01-01

    In this work, an automatic software verification method for Nuclear Power Plant (NPP) protection system is developed. This method utilizes Colored Petri Net (CPN) for system modeling and Prototype Verification System (PVS) for mathematical verification. In order to help flow-through from modeling by CPN to mathematical proof by PVS, an information extractor from CPN models has been developed in this work. In order to convert the extracted information to the PVS specification language, a translator also has been developed. ML that is a higher-order functional language programs the information extractor and translator. This combined method has been applied to a protection system function of Wolsung NPP SDS2 (Steam Generator Low Level Trip). As a result of this application, we could prove completeness and consistency of the requirement logically. Through this work, in short, an axiom or lemma based-analysis method for CPN models is newly suggested in order to complement CPN analysis methods and a guideline for the use of formal methods is proposed in order to apply them to NPP software verification and validation. (author). 9 refs., 15 figs

  14. Targeting the urokinase plasminogen activator receptor inhibits ovarian cancer metastasis.

    Kenny, Hilary A; Leonhardt, Payton; Ladanyi, Andras; Yamada, S Diane; Montag, Anthony; Im, Hae Kyung; Jagadeeswaran, Sujatha; Shaw, David E; Mazar, Andrew P; Lengyel, Ernst

    2011-02-01

    To understand the functional and preclinical efficacy of targeting the urokinase plasminogen activator receptor (u-PAR) in ovarian cancer. Expression of u-PAR was studied in 162 epithelial ovarian cancers, including 77 pairs of corresponding primary and metastatic tumors. The effect of an antibody against u-PAR (ATN-658) on proliferation, adhesion, invasion, apoptosis, and migration was assessed in 3 (SKOV3ip1, HeyA8, and CaOV3) ovarian cancer cell lines. The impact of the u-PAR antibody on tumor weight, number, and survival was examined in corresponding ovarian cancer xenograft models and the mechanism by which ATN-658 blocks metastasis was explored. Only 8% of all ovarian tumors were negative for u-PAR expression. Treatment of SKOV3ip1, HeyA8, and CaOV3 ovarian cancer cell lines with the u-PAR antibody inhibited cell invasion, migration, and adhesion. In vivo, anti-u-PAR treatment reduced the number of tumors and tumor weight in CaOV3 and SKOV3ip1 xenografts and reduced tumor weight and increased survival in HeyA8 xenografts. Immunostaining of CaOV3 xenograft tumors and ovarian cancer cell lines showed an increase in active-caspase 3 and TUNEL staining. Treatment with u-PAR antibody inhibited α(5)-integrin and u-PAR colocalization on primary human omental extracellular matrix. Anti-u-PAR treatment also decreased the expression of urokinase, u-PAR, β(3)-integrin, and fibroblast growth factor receptor-1 both in vitro and in vivo. This study shows that an antibody against u-PAR reduces metastasis, induces apoptosis, and reduces the interaction between u-PAR and α(5)-integrin. This provides a rationale for targeting the u-PAR pathway in patients with ovarian cancer and for further testing of ATN-658 in this indication. ©2010 AACR.

  15. Functional needs which led to the use of digital computing devices in the protection system of 1300 MW units

    Dalle, H.

    1986-01-01

    After a review of classical protection functions used in 900 MW power plants, it is concluded that in order to have functioning margins it is useful to calculate more finely the controled parameters. These calculating needs lead to the use of digital computing devices. Drawing profit from the new possibilities one can improve the general performances of the protection system with regard to availability, safety and maintenance. These options in the case of PALUEL led to the realization of SPIN, described here

  16. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

    Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

    2013-01-01

    Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

  17. [Genetic aspects of premature ovarian failure].

    Warenik-Szymankiewicz, Alina; Słopień, Radosław

    2005-01-01

    Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

  18. Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

    Schildkraut, Joellen M; Goode, Ellen L; Clyde, Merlise A

    2009-01-01

    The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829...

  19. PROTECTIVE EFFECT OF TETRAMETHYLPYRAZINE ON LEARNING AND MEMORY FUNCTION IN D-GALACTOSE-LESIONED MICE

    Chun Zhang; Shi-zhen Wang; Ping-ping Zuo; Xu Cui; Jiong Cai

    2004-01-01

    Objective To explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice.zine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined.Results In this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1)attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice.Conclusion TMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.

  20. Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome

    Sobhana Paramu

    2016-12-01

    Full Text Available Objectives: Anti-mullerian hormone (AMH is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. Materials and Methods: This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. Results: A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p8.3 ng/mL showed a significantly lower ovulation rate (33.3%. LOD was not associated with a risk of diminished ovarian reserve. Conclusion: LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

  1. Pediatric ovarian torsion: an uncommon clinical entity

    Rajwani, Kapil M; Mahomed, Anies

    2014-01-01

    Key Clinical Message Pediatric ovarian torsion is an infrequent diagnosis and it often mimics acute appendicitis. Most cases are due to underlying ovarian pathology and if left untreated, ovarian torsion may eventually cause peritonitis. Emergency exploratory laparoscopy represents a valuable diagnostic and therapeutic tool in suspected ovarian torsion.

  2. Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.

    Pastore, Lisa M; Christianson, Mindy S; Stelling, James; Kearns, William G; Segars, James H

    2018-01-01

    There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.

  3. Evaluation of skin surface hydration state and barrier function of stratum corneum of dorsa of hands and heels treated with PROTECT X2 skin protective cream.

    Kubota, Takahiro

    2012-06-01

    Skin roughness is a term commonly used in Japan to describe a poor skin condition related to a rough and dry skin surface that develops as a result of various damaging effects from the environment or skin inflammation. Recovery from skin roughness requires skin care for a long period, thus it is important to prevent development of such skin changes. PROTECT X2 contains agents used for a protective covering of the skin from frequent hand washing or use of alcohol-based disinfectants. These unique components are also thought to be effective to treat skin roughness of the dorsa of the hands and heels. In the present study, we evaluated the effectiveness of PROTECT X2 to increase skin surface hydration state, as well as enhance the barrier function of the stratum corneum of the dorsa of the hands and heels in elderly individuals. A total of 8 elderly subjects and their caretakers without any skin diseases participated in the study. They applied PROTECT X2 by themselves to the dorsum area of 1 hand and heel 3 to 5 times daily for 1 month, while the opposite sides were left untreated. We measured stratum corneum (SC) hydration and transepidermal water loss (TEWL) before beginning treatment, then 1 week and 1 month after the start of treatment to compare between the treated and untreated skin. SC hydration state after applications of PROTECT X2 was 1.5- to 3.0-fold higher than that of the untreated skin in the dorsa of both hands and heels, indicating that the moisturizing ingredients accompanied by water were replenished in those areas where the cream was applied. Also, TEWL in the dorsum of the hands was 17.0-27.9% lower on the treated side, indicating improvement in SC barrier function. On the basis of these findings, we concluded that PROTECT X2 enhances water-holding in the SC and aids the barrier function of the skin in the dorsum of the hands. In addition, we consider that this formulation is useful for not only protecting the hands from the effects of such agents

  4. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Oommen, Deepu; Yiannakis, Dennis; Jha, Awadhesh N.

    2016-01-01

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  5. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  6. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

  7. Protection of visual functions by human neural progenitors in a rat model of retinal disease.

    David M Gamm

    2007-03-01

    Full Text Available A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat.Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed.Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in

  8. Work, social support and leisure protect the elderly from functional loss: EPIDOSO study.

    d'Orsi, Eleonora; Xavier, André Junqueira; Ramos, Luiz Roberto

    2011-08-01

    To identify risk factors for functional capacity loss in elderly people. Epidoso (Epidemiology of the Elderly) cohort study with elderly people living in São Paulo (Southeastern Brazil). A total of 326 participants in the first interview (1991-1992) who were independent or had mild dependence (one or two activities of daily living) were selected. Those who presented functional loss in the second (1994-1995) or third interviews (1998-1999) were compared to those who did not present it. The incidence of functional loss was calculated according to sociodemographic variables, life habits, cognitive status, morbidity, hospitalization, self-rated health, tooth loss, social support and leisure activities. Crude and adjusted relative risks with 95% confidence intervals were estimated through bivariate and multiple analyses with Poisson regression. The criterion for the inclusion of the variables in the model was p 0.10. The incidence of functional loss was 17.8% (13.6; 21.9). The risk factors in the final model were: age group 70-74 years RR=1.9 (0.9;3.9); age group 75-79 years RR=2.8 (1.4;5.5); age group 80 years or older RR=5.4 (3.0;9.6); score in the mini-mental state examination work RR=0.3 (0.1;1.0); monthly relationship with friends RR=0.5 (0.3;0.8); watching TV RR=0.5 (0.3;0.9); and handcrafting RR=0.7 (0.4;1.0). The prevention of functional loss should include adequate control of chronic diseases, like hypertension, asthma and diabetes, as well as cognitive stimulation. Work, leisure and relationships with friends should be valued due to their protective effect.

  9. Study on Difrarel protecting dark adaptation function in the patients with diabetic retinopathy

    Ying Hui

    2017-03-01

    Full Text Available AIM: To observe the change in full-field electroretinogram(ERGin patients with nonproliferative diabetic retinopathy(NPDRafter panretinal photocoagulation(PRP2d and 2mo, and evaluate the effects of Difrarel protecting dark adaptation function. METHODS: Fifty-five cases with NPDR were randomly divided into the observation group and the control group.Both groups were treated with panretinal photocoagulation.Difrarel tablets was added in the observation group,and Vitamin B was added in the control group. We administered these drugs to the patients for 2mo continuously and the changes in ERG were observed after 2d and 2mo treatment. The amplitude of wave b(bA, and the peak time of wave b(bTwere observed and the data were treated statistically with SPSS 20.0 and test t in pairs. RESULTS: The bT of the two groups before and at 2mo treatment had no difference inner group or inter-group(P>0.05. But there was obvious difference in bA of control group at 2mo after treatment compared with before treatment(PPCONCLUSION: The function of each layer of PDR's retina has been damaged obviously and cannot get well after PRP. The patients with diabetic retinopathy combined with Difrarel tablets and PRP can better restore vision and improve the dark adaptation function.

  10. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Masafumi Koshiyama

    2017-03-01

    Full Text Available Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

  11. Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-03-02

    Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

  12. Po2 cycling protects diaphragm function during reoxygenation via ROS, Akt, ERK, and mitochondrial channels.

    Zuo, Li; Pannell, Benjamin K; Re, Anthony T; Best, Thomas M; Wagner, Peter D

    2015-12-01

    Po2 cycling, often referred to as intermittent hypoxia, involves exposing tissues to brief cycles of low oxygen environments immediately followed by hyperoxic conditions. After experiencing long-term hypoxia, muscle can be damaged during the subsequent reintroduction of oxygen, which leads to muscle dysfunction via reperfusion injury. The protective effect and mechanism behind Po2 cycling in skeletal muscle during reoxygenation have yet to be fully elucidated. We hypothesize that Po2 cycling effectively increases muscle fatigue resistance through reactive oxygen species (ROS), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and certain mitochondrial channels during reoxygenation. Using a dihydrofluorescein fluorescent probe, we detected the production of ROS in mouse diaphragmatic skeletal muscle in real time under confocal microscopy. Muscles treated with Po2 cycling displayed significantly attenuated ROS levels (n = 5; P ROS, Akt, ERK, as well as chemical stimulators to close mitochondrial ATP-sensitive potassium channel (KATP) or open mitochondrial permeability transition pore (mPTP). All these blockers or stimulators abolished improved muscle function with Po2 cycling treatment. This current investigation has discovered a correlation between KATP and mPTP and the Po2 cycling pathway in diaphragmatic skeletal muscle. Thus we have identified a unique signaling pathway that may involve ROS, Akt, ERK, and mitochondrial channels responsible for Po2 cycling protection during reoxygenation conditions in the diaphragm. Copyright © 2015 the American Physiological Society.

  13. Development of an iron-selective antioxidant probe with protective effects on neuronal function.

    Olimpo García-Beltrán

    Full Text Available Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethylpropan-2-yl-2-(7-hydroxy-2-oxo-2H-chromen-4-ylacetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells. CT51 bound Fe2+ with high selectivity and Fe3+ with somewhat lower affinity. Cyclic voltammetric analysis revealed irreversible binding of Fe3+ to CT51, an important finding since stopping Fe2+/Fe3+ cycling in cells should prevent hydroxyl radical production resulting from the Fenton-Haber-Weiss cycle. When added to human neuroblastoma cells, CT51 freely permeated the cell membrane and distributed to both mitochondria and cytoplasm. Intracellularly, CT51 bound iron reversibly and protected against lipid peroxidation. Treatment of primary hippocampal neurons with CT51 reduced the sustained calcium release induced by an agonist of ryanodine receptor-calcium channels. These protective properties of CT51 on cellular function highlight its possible therapeutic use in diseases with significant oxidative, iron and calcium dysregulation.

  14. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model.

    Zhi-Peng Xu

    Full Text Available Alzheimer's disease (AD is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP, dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.

  15. Ultrasonography of ovarian hyperandrogenemia

    Kuzmina, Svetlana A.; Zharkin, Nikolay A.

    2001-05-01

    The method of ultrasonography is high informative and widely used in diagnostics of ovarian hyperandrogenaemia. The majority of authors consider that a hyperplasia of a stroma is the main pathognomonic marker of polycystic ovaries (PCO). Still recently swell of a stroma was valued visually, that had subjective nature. We offer for the first time a way of diagnostics of stromal hyperplasia grounded on measurement of a volume of a stroma and ovary with ultrasound method, calculation of the ratio of a volume of the ovary to a volume of a stroma for every patient.

  16. Discovering Novel Bile Protection Systems in Bifidobacterium breve UCC2003 through Functional Genomics

    Ruiz, Lorena; Zomer, Aldert; O'Connell-Motherway, Mary; van Sinderen, Douwe

    2012-01-01

    Tolerance of gut commensals to bile salt exposure is an important feature for their survival in and colonization of the intestinal environment. A transcriptomic approach was employed to study the response of Bifidobacterium breve UCC2003 to bile, allowing the identification of a number of bile-induced genes with a range of predicted functions. The potential roles of a selection of these bile-inducible genes in bile protection were analyzed following heterologous expression in Lactococcus lactis. Genes encoding three transport systems belonging to the major facilitator superfamily (MFS), Bbr_0838, Bbr_0832, and Bbr_1756, and three ABC-type transporters, Bbr_0406-0407, Bbr_1804-1805, and Bbr_1826-1827, were thus investigated and shown to provide enhanced resistance and survival to bile exposure. This work significantly improves our understanding as to how bifidobacteria respond to and survive bile exposure. PMID:22156415

  17. New proposal on the development of machine protection functions for ITER diagnostics control

    Yamamoto, Tsuyoshi; Yatsuka, Eiichi; Hatae, Takaki; Takeuchi, Masaki; Kitazawa, Sin-iti; Ogawa, Hiroaki; Kawano, Yasunori; Itami, Kiyoshi; Ota, Kazuya; Hashimoto, Yasunori; Nakamura, Kitaru; Sugie, Tatsuo

    2016-01-01

    There is a need to develop ITER instrumentation and control (I and C) systems with high reliabilities. Interlock systems that activate machine protection functions are implemented on robust wired-logic systems such as programmable logic controllers (PLCs). We herein propose a software tool that generates program code templates for the control systems using PLC logic. This tool decreases careless mistakes by developers and increases reliability of the program codes. A large-scale engineering database has been implemented in the ITER project. To derive useful information from this database, we propose adding semantic data to it using the Resource Description Framework format. In our novel proposal for the ITER diagnostic control system, a guide words generator that analyzes the engineering data by inference is applied to the hazard and operability study. We validated the methods proposed in this paper by applying them to the preliminary design for the I and C system of the ITER edge Thomson scattering system. (author)

  18. Grape Seed Proanthocyanidin Extract Prevents Ovarian Aging by Inhibiting Oxidative Stress in the Hens

    Xingting Liu

    2018-01-01

    Full Text Available Oxidative stress is an important inducement in ovarian aging which results in fecundity decline in human and diverse animals. As a potent antioxidant, grape seed proanthocyanidin extract (GSPE was investigated to ameliorate chicken ovarian aging in this study. Firstly, ovarian antioxidant capacity of hens at different ages (90, 150, 280, and 580 days old was compared to elucidate its age-related changes. Subsequently, a D-gal-induced (2.5 mg/mL aging ovarian model was established and the cultured ovarian tissues were treated with GSPE at 5 μg/mL for 72 h to evaluate the putative attenuating effects of GSPE on ovarian aging. Meanwhile, ovaries of D280 (young and D580 (old were treated with GSPE for 72 h in culture to verify the protective effects of GSPE on natural aging ovary. The results showed that GSPE could rescue the antioxidant capacity decline by increasing the antioxidase activities and their gene expression in either D-gal-induced or natural aging ovaries. Moreover, GSPE could maintain the homeostasis between cell proliferation and apoptosis in the D-gal-induced and natural aging ovaries, as well as alleviate D-gal-induced nucleus chromatin condensation in the ovarian granulosa cells. In conclusion, GSPE treatment can effectively prevent the ovarian aging process in hens by reducing oxidative stress.

  19. Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination.

    Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-Ichirou; Kimura, Tadashi

    2017-10-27

    In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer.

  20. Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin

    Babak Litkouhi

    2007-04-01

    Full Text Available BACKGROUND: Claudin-4, a tight junction (TJ protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE, is overexpressed in epithelial ovarian cancer (EOC. Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. METHODS: Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular resistance (Rb in EOC cells after claudin-4 silencing and after C-CPE treatment. RESULTS: Claudin4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose- and claudin-4-dependent noncytotoxic manner. CONCLUSIONS: C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies.

  1. Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue.

    Amorim, Christiani A; Jacobs, Sophie; Devireddy, Ram V; Van Langendonckt, Anne; Vanacker, Julie; Jaeger, Jonathan; Luyckx, Valérie; Donnez, Jacques; Dolmans, Marie-Madeleine

    2013-08-01

    Can a vitrification protocol using an ethylene glycol/dimethyl sulphoxide-based solution and a cryopin successfully cryopreserve baboon ovarian tissue? Our results show that baboon ovarian tissue can be successfully cryopreserved with our vitrification protocol. Non-human primates have already been used as an animal model to test vitrification protocols for human ovarian tissue cryopreservation. Ovarian biopsies from five adult baboons were vitrified, warmed and autografted for 5 months. After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. The influence of the vitrification procedure on the cooling rate was evaluated by a computer model. After vitrification, warming and long-term grafting, follicles were able to grow and maintain their function, as illustrated by Ki67, anti-Müllerian hormone (AMH) and growth differentiation factor-9 (GDF-9) immunostaining. Corpora lutea were also observed, evidencing successful ovulation in all the animals. Stromal tissue quality did not appear to be negatively affected by our cryopreservation procedure, as demonstrated by vascularization and proportions of fibrotic areas, which were similar to those found in fresh ungrafted ovarian tissue. Despite our promising findings, before applying this technique in a clinical setting, we need to validate it by achieving pregnancies. In addition to encouraging results obtained with our vitrification procedure for non-human ovarian tissue, this study also showed, for the first time, expression of AMH and GDF-9 in ovarian follicles. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4507.10, grant 3.4.590.08 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Department of Mechanical Engineering at Louisiana State University (support to Ram Devireddy), and

  2. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to...

  3. Fertility drugs and ovarian cancer.

    Ali, Aus Tariq

    2017-06-20

    The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Accidental ovarian autograft after a laparoscopic surgery: case report.

    Marconi, G; Quintana, R; Rueda-Leverone, N G; Vighi, S

    1997-08-01

    To report an autograft of ovarian tissue in the incision of the surgical trocar during laparoscopic surgery and to assess the potentiality of grafting of ovarian parenchyma in nonpelvic tissue in humans. A case report. Instituto de Fertilidad y Ginecología de Buenos Aires (IFER), Buenos Aires, Argentina. Infertile patient undergoing surgery due to an endometriotic cyst of the left ovary. Laparoscopic cystectomy. Accidental retention of a portion of the capsule and adjacent ovarian tissue of the endometrioma in SC cellular tissue. Months after surgery, a SC tumor was formed under the surgical incision. It was subsequently excised. Observation of tumor growth during menstrual cycles and ovulation induction; anatomopathologic study of the tissue after its extirpation. The tumor grew spontaneously in the periovulatory period and during treatments of ovulation induction. The anatomopathologic report of the tumor, removed 15 months after the first surgery, revealed functioning ovarian tissue with vessels of neoformation. This is the first description of autografted ovarian tissue in humans. We describe that the ovary can maintain its ovulatory function even in the absence of its pedicel. Also, we suggest that extirpation of surgical material through the incision of the trocar is not recommended, as the possibility of "sowing" or of autografts may occur.

  5. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-01-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E 2 ) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E 2 dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E 2 increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab

  6. Percutaneous renal angioplasty and stenting: application of embolic protection device in patients with normal renal function

    Tong Xiaoqiang; Yang Ming; Wang Jian; Song Li; Wang Chao; Lv Yongxing; Sun Hongliang; Zou Yinghua; Yin Ming

    2007-01-01

    Objective: To investigate the Value of embolic protection device (EPD)in renal artery stenting (RAS)for the patients with normal renal function. Methods: Total 24 patients (26 renal arteries) suffering from renal artery stenosis with normal serum creatinine were divided into two groups: EPD group (n12)and non-EPD group (n=12). Serum creatinine was calculated and analized statistically between the two groups, 1 month and 6months after stenting respectively, and followed by comparisons taking inside of each group and between both groups. Results: Serum creatinine of the EPD and non-EPD groups before, 1 month and 6 month after stenting were(99.18 ± 18.26) μmol/L, (101.73 ± 12.65) μmol/L, (96.82 ± 15.81) μmol/L and (100.18 ± 19.81) μmol/L, (107.36 ± 29.49) μmol/L, (127.64 ± 88.05) μmol/L, respectively; showing no significant difference inside each group individually (P>0.05), and also no statistically significant difference between the two groups (P>0.05). Conclusion: For the patients suffering from renal artery stenosis with normal serum creatinine, application of EPD may have no impact on renal function. Further evaluation is needed. (authors)

  7. DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions.

    Lambrughi, Matteo; De Gioia, Luca; Gervasio, Francesco Luigi; Lindorff-Larsen, Kresten; Nussinov, Ruth; Urani, Chiara; Bruschi, Maurizio; Papaleo, Elena

    2016-11-02

    Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    Zheng, Hong; Liu, Jia-Yu; Song, Feng-Ju; Chen, Ke-Xin

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer

  9. Protecting the environment for development: Linking ecosystem structure & function and development outcomes

    Claassen, Marius

    2017-01-01

    Full Text Available edition of National Water Resource Strategy sets out to ensure that South Africa's aquatic ecosystems are protected effectively at different levels in accordance with the classification system, and that decisions concerning levels of protection take...

  10. Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

    Alborzi, S; Khodaee, R; Parsanejad, M E

    2001-09-01

    To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

  11. Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

    Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

    2018-04-01

    To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

  12. Activated ovarian endothelial cells promote early follicular development and survival.

    Kedem, Alon; Aelion-Brauer, Anate; Guo, Peipei; Wen, Duancheng; Ding, Bi-Sen; Lis, Raphael; Cheng, Du; Sandler, Vladislav M; Rafii, Shahin; Rosenwaks, Zev

    2017-09-19

    New data suggests that endothelial cells (ECs) elaborate essential "angiocrine factors". The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development. Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50-150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed. After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia. This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication. In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential "angiocrine factors" involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.

  13. The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection

    Deborah M. Brown

    2016-03-01

    Full Text Available CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL play a role in chronic, as well as, acute infections such as influenza A virus (IAV infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections such as HIV, mouse pox, murine gamma herpes virus, CMV, EBV and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and anti-tumor immunity through their ability to acquire perforin mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other anti-viral and anti-tumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell mediated immune protection against heterosubtypic IAV infection.

  14. Assessing the protection function of Alpine forest ecosystems using BGC modelling theory

    Pötzelsberger, E.; Hasenauer, H.; Petritsch, R.; Pietsch, S. A.

    2009-04-01

    The purpose of this study was to assess the protection function of forests in Alpine areas by modelling the flux dynamics (water, carbon, nutrients) within a watershed as they may depend on the vegetation pattern and forest management impacts. The application case for this study was the catchment Schmittenbach, located in the province of Salzburg. Data available covered the hydrology (rainfall measurements from 1981 to 1998 and runoff measurements at the river Schmittenbach from 1981 to 2005), vegetation dynamics (currently 69% forest, predominantly Norway Spruce). The method of simulating the forest growth and water outflow was validated. For simulations of the key ecosystem processes (e.g. photosynthesis, carbon and nitrogen allocation in the different plant parts, litter fall, mineralisation, tree water uptake, transpiration, rainfall interception, evaporation, snow accumulation and snow melt, outflow of spare water) the biogeochemical ecosystem model Biome-BGC was applied. Relevant model extensions were the tree species specific parameter sets and the improved thinning regime. The model is sensitive to site characteristics and needs daily weather data and information on the atmospheric composition, which makes it sensitive to higher CO2-levels and climate change. For model validation 53 plots were selected covering the full range of site quality and stand age. Tree volume and soil was measured and compared with the respective model results. The outflow for the watershed was predicted by combining the simulated forest-outflow (derived from plot-outflow) with the outflow from the non-forest area (calculated with a fixed outflow/rainfall coefficient (OC)). The analysis of production and water related model outputs indicated that mechanistic modelling can be used as a tool to assess the performance of Alpine protection forests. The Water Use Efficiency (WUE), the ratio of Net primary production (NPP) and Transpiration, was found the highest for juvenile stands (

  15. An Assessment of the Self-Protective Function of Self-Handicapping.

    Steinhauer, Annie; And Others

    Self-handicapping is the phenomenon of setting oneself up to fail a feared evaluation task to protect a sense of self-worth. A study examined whether individuals self-handicap to protect a general or global perception of themselves or to protect perceptions of competence in the specific domain being evaluated. Handicapping behaviors related to…

  16. Soil surface protection by Biocrusts: effects of functional groups on textural properties

    Concostrina-Zubiri, Laura; Huber-Sannwald, Elisabeth; Martínez, Isabel; Flores Flores, José Luis; Escudero, Adrián

    2015-04-01

    In drylands, where vegetation cover is commonly scarce, soil surface is prone to wind and water soil erosion, with the subsequent loss of topsoil structure and chemical properties. These processes are even more pronounced in ecosystems subjected to extra erosive forces, such as grasslands and rangelands that support livestock production. However, some of the physiological and functional traits of biocrusts (i.e., complex association of cyanobacteria, lichens, mosses, fungi and soil particles) make them ideal to resist in disturbed environments and at the same time to protect soil surface from mechanical perturbations. In particular, the filaments and exudates of soil cyanobacteria and the rhizines of lichen can bind together soil particles, forming soil aggregates at the soil surface and thus enhancing soil stability. Also, they act as "biological covers" that preserve the most vulnerable soil layer from wind and runoff erosion and raindrop impact, maintaining soil structure and composition. In this work, we evaluated soil textural properties and organic matter content under different functional groups of biocrusts (i.e., cyanobacteria crust, 3 lichen species, 1 moss species) and in bare soil. In order to assess the impact of livestock trampling on soil properties and on Biocrust function, we sampled three sites conforming a disturbance gradient (low, medium and high impact sites) and a long-term livestock exclusion as control site. We found that the presence of biocrusts had little effects on soil textural properties and organic matter content in the control site, while noticeable differences were found between bare soil and soil under biocrusts (e.g., up to 16-37% higher clay content, compared to bare soil and up to 10% higher organic matter content). In addition, we found that depending on morphological traits and grazing regime, the effects of biocrusts changed along the gradient. For example, soil under the lichen Diploschistes diacapsis, with thick thallus

  17. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome

    Nunez, María I; Mills, Gordon B; Aldaz, C Marcelo; Rosen, Daniel G; Ludes-Meyers, John H; Abba, Martín C; Kil, Hyunsuk; Page, Robert; Klein-Szanto, Andres JP; Godwin, Andrew K; Liu, Jinsong

    2005-01-01

    The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1. This region is a frequent target for loss of heterozygosity and chromosomal rearrangement in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The goal of these studies was to evaluate WWOX protein expression levels in ovarian carcinomas to determine if they correlated with clinico-pathological parameters, thus providing additional support for WWOX functioning as a tumor suppressor. We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by χ 2 test with Yates' correction. The basic significance level was fixed at p < 0.05. Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70%) stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status (p = 0.008) and shorter overall survival (p = 0.03). These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of

  18. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours

    Leary, A. F.; Quinn, M.; Fujiwara, K.; Coleman, R. L.; Kohn, E.; Sugiyama, T.; Glasspool, R.; Ray-Coquard, I.; Colombo, N.; Bacon, M.; Zeimet, A.; Westermann, A.; Gomez-Garcia, E.; Provencher, D.; Welch, S.; Small, W.; Millan, D.; Okamoto, A.; Stuart, G.; Ochiai, K.

    2017-01-01

    This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian

  19. TO METHODOLOGY FOR IMPROVEMENT OF ACTIVE VIBRO-PROTECTION WHILE USING FUNCTIONAL DIAGNOSTICS

    T. N. Mikulik

    2014-01-01

    Full Text Available The paper investigates vibro-protection conditions for “operator-chair” system of a transport facility (“Belarus-tractorfamily. Experimental  research for the system vibroloading with due account of elastic shock-absorbing characteristics, operator’s comfortability. The paper has made it possible to determine a range of the system vibration frequency which is badlysustained by the operator because the last is located in the zone of natural frequency of human visceral organs vibrationsInfluence of physiological operator’s factors – heartbeat rate, variational height, mode amplitude, stress index has been investigated on the basis of a factor experiment and correlation dependences have been obtained in the paper. The developed methodology for investigation of algorithmic provision pertaining to better active vibroprotection of the “operator-chair” system presupposes an availability of mathematical model used for synthesis of control laws and selection of algorithms for formation of signals on physiological operator’s state. Structural algorithm scheme for vibroprotection of “driver – seat – road” system has been drawn in the paper. Harmonic sinusoidal and poly-harmonic disturbances from the side of a power unit and discrete algorithms based on filtration of white noise with a linear filter and  prescribed correlation function have been accepted as a mathematical model for external environment disturbances. In case of harmonic excitation of “operator – chair” system  a force transferred to the system by a shock-absorber and also shock-absorber efficiency evaluation in the form of force transmission coefficient and vibration insulation value are estimated at decibels. Fourier’s series describes motion of the system in case of vibration forces initiated by the operation of the power unit. Piecewise-linear function describes a reaction on impact excitation of the system when final change in speed and motion

  20. Epigenetic Characterization of Ovarian Cancer

    Murphy, Susan K

    2005-01-01

    .... The approach is to use normal ovarian surface epithelium (NOSE) and malignant cells obtained directly from surgically removed specimens in order to most closely approximate the methylation status in vivo...

  1. Ovarian torsion: Echographic discoveries

    Triana R, Gustavo; Navas O, Claudia

    1994-01-01

    Patient of 31 years who consulted to the even service of urgencies to present of two hours of evolution intense pain in flank and region lumbar left, associated to vomit, present square similar 5 previous days to the entrance in the right side. Go Po, plans with DIU FUR, 8 previous days to the square. It is practiced Tran abdominal pelvic echography that shows left ovary of 6 x 5 x 3 cms, with multiple follicular images, of thick walls, with I liquidate free abdominal, highly suggestive of ovarian torsion although the patient didn't present square of sharp abdomen. It decides to suspend analgesic and to value it, presented sharp abdominal pain, reason why laparotomy was practiced, finding mass of 6 x 6 cms. of necrotic aspect, corresponding to the left ovary, which presented three turns on their axis. It is taken finish left salpingooferectomy

  2. [Association between obesity and ovarian cancer].

    Valladares, Macarena; Corsini, Gino; Romero, Carmen

    2014-05-01

    Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.

  3. Management of ovarian cysts in infants.

    Xue-Qiang, Yan; Nan-Nan, Zheng; Lei, Yu; Wei, Lu; Hong-Qiang, Bian; Jun, Yang; Xu-Fei, Duan; Xin-Ke, Qin

    2015-12-01

    To discuss the experience of diagnosis and treatment of ovarian cyst in infants. A retrospective review was conducted on 20 infants who suffered from ovarian cyst. There were no dysplasia ovarian was found in children which were preoperatively diagnosed simplex cyst. Within thirteen children preoperatively detected mixed cystic-solid lesion, six cases ovarian cysts disappeared and two cases underwent poor blood supply in the following time. Adverse effects for ovarian cyst in infants can be prevented by agressive surgical intervention. Harmful effects of ovarian cyst can be prevented by positive surgical intervention despite the diagnostic difficulties in children with clinical symptoms of this condition.

  4. Premature ovarian failure

    Vujović Svetlana

    2012-01-01

    Full Text Available Premature ovarian failure (POF is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc. The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone, karyotype (<30 years of age, ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

  5. Acne tarda and male-pattern baldness unmasking primary ovarian insufficiency: a case and review.

    Zouboulis, Christos C; Achenbach, Alexander; Makrantonaki, Eugenia

    2014-01-01

    A 30-year-old woman presented with recurrent acne lesions and progressing male-pattern baldness. Furthermore, she reported amenorrhea, weight loss, mucosal xerosis and dyspareunia since discontinuation of hormonal contraception 6 months earlier in order to conceive. Acne tarda and androgenetic alopecia of female pattern were diagnosed. Hormonal and immunologic serological and ultrasound examinations revealed an autoimmune hypergonadotropic primary ovarian insufficiency (POI) with no ovarian cysts but ovarian fibrosis with marked reduced follicle pool. Immediate ovarian stimulation and in vitro fertilization led to pregnancy and the patient gave birth to a healthy child. Though presenting with clinical findings similar to menopause, 50% of patients with POI exhibit varying and unpredictable ovarian function, and only 5-10% are able to accomplish pregnancy. Genetic disorders affect the X chromosome. In 14-30% of cases POI has been associated with autoimmunity. POI may occur after discontinuation of hormonal contraception, like in our case.

  6. Hormone therapy and ovarian cancer

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  7. Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

    Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

    2018-06-01

    Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Protective effect study of polysaccharides from tremella fuciformis on hematopoietic function in radiation-injured mice

    Xu, Wen-qing; Yang, Fu-jun; Shen, Xiu; Wang, Yue-ying; Liu, Pei-xun

    2008-01-01

    A kind of water-soluble homogeneous polysaccharide named as TFB was isolated and purified from Tremella Fuciformis by DEAE-Sephadex A-25 and Sephadex G-150. Its chemical and physical characteristics was determined by chemical methods, gas chromatography, mass spectrum and size exclusion chromatography. Colony-forming unit of spleen(CFU-S), number of nucleated cells in bone marrow (BMNC) and spleen index were adopted to investigate the effect on hematopoietic function of TFB at 6 mg/kg, 12 mg/kg, 24 mg/kg in mice irradiated with 7.5 Gy 137 Cs γ-rays. The results indicated that TFB is composed of glucose, mannose and serine in closely molar ratios of 8:2:0.1. Its relative molecular weight is estimated to be 68,000 by HPGPC. Its main chain is comprised of 1,4 linked glucose and 1,2,3,4,6 linked mannose, the branch point is at the site of mannose. Side chain is comprised of terminal glucose, Serine, H 2 N-1,4,6 linked mannose. Glucose uronic acid may be in main chain because of its 32.88 % content. The numbers of nucleated cells in bone marrow, colony-forming unit of spleen and spleen index increased markedly compared with the negative control group in mice treated with WTF-B administered 6 mg/kg ip. for three days prior to 137 Cs-γray irradiation, and the number of nucleated cells in bone marrow increased markedly but the CFU-S manifested no difference in mice treated with WTF-B administered 12 mg/kg and 24 mg/kg ip. compared with the negative control group. We can make conclusion that Polysaccharides of Tremella fuciformis has protective effects on hematopoietic function in radiation-injured mice, its optimal dose is 6 mg/kg. (author)

  9. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. © 2014 The Authors. The Journal of Physiology © 2014

  10. Physical protection

    Myers, D.A.

    1989-01-01

    Physical protection is defined and its function in relation to other functions of a State System of Accounting for and Control of Nuclear Materials is described. The need for a uniform minimum international standard for physical protection as well as the need for international cooperation in physical protection is emphasized. The IAEA's INFCIRC/225/Rev. 1 (Annex 1) is reviewed. The Convention on the Physical Protection of Nuclear Material (Annex 2) is discussed. Photographs show examples of typical physical protection technology (Annex 3)

  11. Radial basis function networks applied to DNBR calculation in digital core protection systems

    Lee, Gyu-Cheon; Heung Chang, Soon

    2003-01-01

    The nuclear power plant has to be operated with sufficient margin from the specified DNBR limit for assuring its safety. The digital core protection system calculates on-line real-time DNBR by using a complex subchannel analysis program, and triggers a reliable reactor shutdown if the calculated DNBR approaches the specified limit. However, it takes a relatively long calculation time even for a steady state condition, which may have an adverse effect on the operation flexibility. To overcome the drawback, a new method using a radial basis function network is presented in this paper. Nonparametric training approach is utilized, which shows dramatic reduction of the training time, no tedious heuristic process for optimizing parameters, and no local minima problem during the training. The test results show that the predicted DNBR is within about ±2% deviation from the target DNBR for the fixed axial flux shape case. For the variable axial flux case including severely skewed shapes that appeared during accidents, the deviation is within about ±10%. The suggested method could be the alternative that can calculate DNBR very quickly while guaranteeing the plant safety

  12. Protective function of complement against alcohol-induced rat liver damage.

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  13. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

    Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

    2008-10-01

    The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.

  14. Coating fabrics with gold nanorods for colouring, UV-protection, and antibacterial functions

    Zheng, Yidan; Xiao, Manda; Jiang, Shouxiang; Ding, Feng; Wang, Jianfang

    2012-12-01

    Gold nanorods exhibit rich colours owing to the nearly linear dependence of the longitudinal plasmon resonance wavelength on the length-to-diameter aspect ratio. This property of Au nanorods has been utilized in this work for dyeing fabrics. Au nanorods of different aspect ratios were deposited on both cotton and silk fabrics by immersing them in Au nanorod solutions. The coating of Au nanorods makes the fabrics exhibit a broad range of colours varying from brownish red through green to purplish red, which are essentially determined by the longitudinal plasmon wavelength of the deposited Au nanorods. The colorimetric values of the coated fabrics were carefully measured for examining the colouring effects. The nanorod-coated cotton fabrics were found to be commercially acceptable in washing fastness to laundering tests and colour fastness to dry cleaning tests. Moreover, the nanorod-coated cotton and silk fabrics show significant improvements on both UV-protection and antibacterial functions. Our study therefore points out a promising approach for the use of noble metal nanocrystals as dyeing materials for textile applications on the basis of their inherent localized plasmon resonance properties.

  15. The Unexpected Ovarian Pregnancy at Laparoscopy: A Review of Management

    Meher Tabassum

    2017-01-01

    Full Text Available Ovarian ectopic pregnancies are a rare occurrence; however the incidence is on the rise. Preoperative diagnosis remains difficult due to nonspecific clinical symptoms and USS findings. Most patients undergo diagnostic laparoscopy with subsequent surgical management. We present the case of a 32-year-old female who presented with vaginal bleeding and an unsited pregnancy, with a BhCG of 24693. Formal USS described unruptured right tubal ectopic with ovarian pregnancy being diagnosed at laparoscopy. A wedge resection was conducted to preserve ovarian function. Postoperative recovery was uneventful and BhCG levels returned to zero (nonpregnant in an outpatient setting. Although laparoscopy remains the gold standard of diagnosis and treatment, in this case report we discuss benefits of early diagnosis for fertility conserving management, including nonsurgical options.

  16. The Unexpected Ovarian Pregnancy at Laparoscopy: A Review of Management.

    Tabassum, Meher; Atmuri, Kiran

    2017-01-01

    Ovarian ectopic pregnancies are a rare occurrence; however the incidence is on the rise. Preoperative diagnosis remains difficult due to nonspecific clinical symptoms and USS findings. Most patients undergo diagnostic laparoscopy with subsequent surgical management. We present the case of a 32-year-old female who presented with vaginal bleeding and an unsited pregnancy, with a BhCG of 24693. Formal USS described unruptured right tubal ectopic with ovarian pregnancy being diagnosed at laparoscopy. A wedge resection was conducted to preserve ovarian function. Postoperative recovery was uneventful and BhCG levels returned to zero (nonpregnant) in an outpatient setting. Although laparoscopy remains the gold standard of diagnosis and treatment, in this case report we discuss benefits of early diagnosis for fertility conserving management, including nonsurgical options.

  17. Cytogenetic abnormalities in Tunisian women with premature ovarian failure.

    Ayed, Wiem; Amouri, Ahlem; Hammami, Wajih; Kilani, Olfa; Turki, Zinet; Harzallah, Fatma; Bouayed-Abdelmoula, Nouha; Chemkhi, Imen; Zhioua, Fethi; Slama, Claude Ben

    2014-12-01

    To identify the distribution of chromosome abnormalities among Tunisian women with premature ovarian failure (POF) referred to the department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia), standard cytogenetic analysis was carried out in a total of 100 women younger than 40 affected with premature ovarian failure. We identified 18 chromosomal abnormalities, including seven X-numerical anomalies in mosaic and non-mosaic state (45,X; 47,XXX), four sex reversal, three X-structural abnormalities (terminal deletion and isochromosomes), one autosomal translocation and one supernumerary marker. The overall prevalence of chromosomal abnormalities was 18% in our cohort. X chromosome aneuploidy was the most frequent aberration. This finding confirms the essential role of X chromosome in ovarian function and underlies the importance of cytogenetic investigations in the routine management of POF. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  18. Form and Function in Doing Business Rankings: is Investor Protection in Italy Still so Bad?

    Luca Enriques; Matteo Gargantini

    2016-01-01

    The World Bank’s Doing Business Report (DBR) ranks every year numerous jurisdictions across the globe according to their ability to facilitate business activities. Among the indexes contributing to the definition of the global competitiveness of the legislations, the “Protecting investors index” (PII) measures the protection of minority shareholders in listed companies. In this paper, we analyse the DBR’s assessment of the Italian regulatory framework on investor protection. We find that the ...

  19. Disturbed growth and selection of the human ovarian follicle

    T.D. Pache

    1993-01-01

    textabstractThe first objective of this stody was to review some aspects of current knowledge of ovarian function in normal menstrual cycles. A discussion of the anatomy and physiology of the normal ovary can be found in chapter 2. The second objective was to provide new information about the

  20. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer : design and methodological challenges

    Overbeek, Annelies; van den Berg, Marleen H.; Kremer, Leontien C. M.; van den Heuvel-Eibrink, Marry M.; Tissing, Wim J. E.; Loonen, Jacqueline J.; Versluys, Birgitta; Bresters, Dorine; Kaspers, Gertjan J. L.; Lambalk, Cornelis B.; van Leeuwen, Flora E.; van Dulmen-den Broeder, Eline

    2012-01-01

    Background: Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered

  1. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

    Overbeek, A.; van den Berg, M.H.; Kremer, L.C.; van den Heuvel-Eibrink, M.; Tissing, W.J.; Loonen, J.J.; Versluys, B.; Bresters, D.; Kaspers, G.J.L.; Lambalk, C.B.; van Leeuwen, F.E.; van Dulmen-den Broeder, E.

    2012-01-01

    Background: Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered

  2. Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling

    Bhattacharya, Poulomi, E-mail: poulomib@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Sen, Nivedita, E-mail: nsen@email.arizona.edu [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Hoyer, Patricia B., E-mail: Hoyer@u.arizona.edu [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States)

    2012-01-01

    4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. -- Highlights: ► Ovarian mEH functions to metabolize VCD to a less toxic compound. ► mEH expression is increased in a temporal pattern in response to VCD exposure. ► PI3K signaling is involved in regulation of ovarian mEH expression.

  3. Recovery of ovarian function after postradiation menopause. Do FSH levels have a definitive prognostic value?; Recuperation de fonctionnement ovarien apres menopause radio-induite. L`hormone folliculostimulante (FSH) a-t-elle une valeur pronostique definitive?

    Letur-Konirsch, H. [Hopital Necker-Enfants-Malades, 75 - Paris (France); Guis, F. [Hopital Antoine-Beclere, Clamart (France)

    1996-08-01

    Menopause, conventionally defined as the permanent cessation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogeneic bone marrow transplantation for acute immuno-blastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular developments, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor. (author). 13 refs.

  4. Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

    Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

    2016-01-22

    Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

  5. Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

    Gai, Muhuizi; Bo, Qifang; Qi, Lixia

    2016-01-01

    Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

  6. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  7. [Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

    Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

    2013-01-20

    The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

  8. Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: Protective and deleterious effects

    Grivennikov, Sergei I.; Tumanov, Alexei V.; Liepinsh, Dmitry J.; Kruglov, Andrei A.; Marakusha, Boris I.; Shakhov, Alexander N.; Murakami, Takaya; Drutskaya, Ludmila N.; Förster, Irmgard; Clausen, Björn E.; Tessarollo, Lino; Ryffel, Bernhard; Kuprash, Dmitry V.; Nedospasov, Sergei A.

    2005-01-01

    Tumor necrosis factor (TNF, TNFalpha) is implicated in various pathophysiological processes and can be either protective, as in host defense, or deleterious, as in autoimmunity or toxic shock. To uncover the in vivo functions of TNF produced by different cell types, we generated mice with TNF

  9. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

    Flannick, Jason; Thorleifsson, Gudmar; Beer, Nicola L

    2014-01-01

    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating va...

  10. Stage at diagnosis and ovarian cancer survival

    Maringe, Camille; Walters, Sarah; Butler, John

    2012-01-01

    We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival.......We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival....

  11. Sunburn protection as a function of sunscreen application thickness differs between high and low SPFs.

    Liu, Wei; Wang, Xuemin; Lai, Wei; Yan, Tian; Wu, Yanyu; Wan, Miaojian; Yi, Jinling; Matsui, Mary S

    2012-06-01

    Sunscreens are an important component of healthy sun-protection behavior. To achieve satisfactory protection, sunscreens must be applied consistently, evenly and correctly. Consumers do not apply sunscreen properly and, therefore, do not achieve the protection indicated by the label 'sun protection factor' (SPF). The objective of the present study was to determine the actual sun(burn) protection given by a range of sunscreen application thickness levels for both low and high SPF formulas. Forty study subjects were recruited from each of three geographical regions in China. Sunscreens with label SPFs of 4, 15, 30, and 55 were tested at application levels of 0.5, 1.0, 1.5, and 2.0 mg/cm(2) in three laboratories using a standard SPF protocol. Sunscreens with lower SPFs (4 and 15) showed a linear dose-response relationship with application level, but higher SPF (30 and 55) product protection was exponentially related to application thickness. Sunscreen protection is not related in one uniform way to the amount of product applied to human skin. Consumers may achieve an even lower than expected sunburn protection from high SPF products than from low SPF sunscreens. © 2012 John Wiley & Sons A/S.

  12. (Another Bankruptcy Legislation reform - functionalization of bankruptcy legal protection or placebo effect?

    Dejan Bodul

    2015-01-01

    Full Text Available The paper deals with the most current topic in the field of collective civil law protection. The reforms of the Bankruptcy Act (seven of them as well as implementation of the Financial Operations and Pre-Bankruptcy Settlements Act (three amendments, which were implemented in 2012, have significantly altered Croatian insolvency legislation. Nevertheless, the indicative methods of determining the facts show that the bankruptcy and preliminary bankruptcy procedures, in relation to other countries in the region, are consuming less time. They are more expensive and have lower satisfaction from creditors. In comparison to countries with developed bankruptcy systems, Croatian regulations still need improvement. One has to take into consideration a substantial impact of multiple external, institutional factors on legislative solutions (unfavourable social context, problems in the payment system, the precarious recordings of immovable and movable property, an insufficient number of judges who were entrusted with the liquidation proceedings, weak training of bankruptcy administrators, inadequate methods of financing, and consequently weak motivation to work. The legislators are planning to make another functionalization of the Bankruptcy Act. His intention is, after two years of experimentation in the Financial Operations and Pre-Bankruptcy Settlements Act, to accept provisions on pre-bankruptcy settlements and reinstate many pre-existing options in the preparation of the reorganization plan. Since the existing framework is not allowing for a detailed analysis of the aforementioned subjects, one must emphasize that the space here does not permit a detailed analysis of these issues. Therefore, authors of this article will deal with subjects they see as relevant and essential for understanding key issues within the domain of the Bankruptcy Act. This work has been supported by the Croatian science foundation under the project number 6558 "Business and

  13. Protections of bovine serum albumin protein from damage on functionalized graphene-based electrodes by flavonoids.

    Sun, Bolu; Gou, Yuqiang; Xue, Zhiyuan; Zheng, Xiaoping; Ma, Yuling; Hu, Fangdi; Zhao, Wanghong

    2016-05-01

    A sensitive electrochemical sensor based on bovine serum albumin (BSA)/poly (diallyldimethylammonium chloride) (PDDA) functionalized graphene nanosheets (PDDA-G) composite film modified glassy carbon electrode (BSA/PDDA-G/GCE) had been developed to investigate the oxidative protein damage and protections of protein from damage by flavonoids. The performance of this sensor was remarkably improved due to excellent electrical conductivity, strong adsorptive ability, and large effective surface area of PDDA-G. The BSA/PDDA-G/GCE displayed the greatest degree of BSA oxidation damage at 40 min incubation time and in the pH 5.0 Fenton reagent system (12.5 mM FeSO4, 50 mM H2O2). The antioxidant activities of four flavonoids had been compared by fabricated sensor based on the relative peak current ratio of SWV, because flavonoids prevented BSA damage caused by Fenton reagent and affected the BSA signal in a solution containing Co(bpy)3(3+). The sensor was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). UV-vis spectrophotometry and FTIR were also used to investigate the generation of hydroxyl radical and BSA damage, respectively. On the basis of results from electrochemical methods, the order of the antioxidant activities of flavonoids is as follows: (+)-catechin>kaempferol>apigenin>naringenin. A novel, direct SWV analytical method for detection of BSA damage and assessment of the antioxidant activities of four flavonoids was developed and this electrochemical method provided a simple, inexpensive and rapid detection of BSA damage and evaluation of the antioxidant activities of samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Protections of bovine serum albumin protein from damage on functionalized graphene-based electrodes by flavonoids

    Sun, Bolu; Gou, Yuqiang; Xue, Zhiyuan; Zheng, Xiaoping; Ma, Yuling; Hu, Fangdi; Zhao, Wanghong

    2016-01-01

    A sensitive electrochemical sensor based on bovine serum albumin (BSA)/poly (diallyldimethylammonium chloride) (PDDA) functionalized graphene nanosheets (PDDA-G) composite film modified glassy carbon electrode (BSA/PDDA-G/GCE) had been developed to investigate the oxidative protein damage and protections of protein from damage by flavonoids. The performance of this sensor was remarkably improved due to excellent electrical conductivity, strong adsorptive ability, and large effective surface area of PDDA-G. The BSA/PDDA-G/GCE displayed the greatest degree of BSA oxidation damage at 40 min incubation time and in the pH 5.0 Fenton reagent system (12.5 mM FeSO_4, 50 mM H_2O_2). The antioxidant activities of four flavonoids had been compared by fabricated sensor based on the relative peak current ratio of SWV, because flavonoids prevented BSA damage caused by Fenton reagent and affected the BSA signal in a solution containing Co(bpy)_3"3"+. The sensor was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). UV–vis spectrophotometry and FTIR were also used to investigate the generation of hydroxyl radical and BSA damage, respectively. On the basis of results from electrochemical methods, the order of the antioxidant activities of flavonoids is as follows: (+)-catechin > kaempferol > apigenin > naringenin. A novel, direct SWV analytical method for detection of BSA damage and assessment of the antioxidant activities of four flavonoids was developed and this electrochemical method provided a simple, inexpensive and rapid detection of BSA damage and evaluation of the antioxidant activities of samples. - Highlights: • Hydroxyl radicals were produced by Fenton reagents. • An electrochemical bovine serum albumin (BSA) damage sensor was successfully fabricated. • The proposed biosensor can assess the antioxidant capacity of four flavonoids. • The order of antioxidant activities of flavonoids is

  15. Protections of bovine serum albumin protein from damage on functionalized graphene-based electrodes by flavonoids

    Sun, Bolu [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Gou, Yuqiang [Lanzhou Military Command Center for Disease Prevention and Control, Lanzhou 730000 (China); Xue, Zhiyuan; Zheng, Xiaoping; Ma, Yuling [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Hu, Fangdi, E-mail: hufd@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Wanghong, E-mail: wanghongzhao@sina.com [Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 51515 (China)

    2016-05-01

    A sensitive electrochemical sensor based on bovine serum albumin (BSA)/poly (diallyldimethylammonium chloride) (PDDA) functionalized graphene nanosheets (PDDA-G) composite film modified glassy carbon electrode (BSA/PDDA-G/GCE) had been developed to investigate the oxidative protein damage and protections of protein from damage by flavonoids. The performance of this sensor was remarkably improved due to excellent electrical conductivity, strong adsorptive ability, and large effective surface area of PDDA-G. The BSA/PDDA-G/GCE displayed the greatest degree of BSA oxidation damage at 40 min incubation time and in the pH 5.0 Fenton reagent system (12.5 mM FeSO{sub 4}, 50 mM H{sub 2}O{sub 2}). The antioxidant activities of four flavonoids had been compared by fabricated sensor based on the relative peak current ratio of SWV, because flavonoids prevented BSA damage caused by Fenton reagent and affected the BSA signal in a solution containing Co(bpy){sub 3}{sup 3+}. The sensor was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). UV–vis spectrophotometry and FTIR were also used to investigate the generation of hydroxyl radical and BSA damage, respectively. On the basis of results from electrochemical methods, the order of the antioxidant activities of flavonoids is as follows: (+)-catechin > kaempferol > apigenin > naringenin. A novel, direct SWV analytical method for detection of BSA damage and assessment of the antioxidant activities of four flavonoids was developed and this electrochemical method provided a simple, inexpensive and rapid detection of BSA damage and evaluation of the antioxidant activities of samples. - Highlights: • Hydroxyl radicals were produced by Fenton reagents. • An electrochemical bovine serum albumin (BSA) damage sensor was successfully fabricated. • The proposed biosensor can assess the antioxidant capacity of four flavonoids. • The order of antioxidant

  16. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.

    Konstantin V Salojin

    Full Text Available Mammalian sterile 20-like kinase 1 (Mst1 is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.

  17. Ovarian preservation in children for adenexal pathology, current trends in laparoscopic management and our experience

    Preet Agarwal

    2014-01-01

    Full Text Available Aims: Primary cysts and tumors of the ovary alongwith torsion are often regarded as an indication for open oophorectomy because of the fear of leaving an ischemic organ inside and chances of recurrence. We wish to report our experience of both modalities of management where we initially removed adenexal torsion by either laparoscopic salpingo-oophorectomy or oophorectomy, but later followed a more conservative approach of adenexal lesion removal with ovarian preservation. Materials and Methods: Retrospective review of clinical records of patients with ovarian pathology who were managed laparoscopically. Results: 46 cases of pediatric ovarian pathology were managed between March 2006 and March 2013 in two centers by a team of surgeons. The age ranged from 1 days to 18 years (average 14.3 years and the pathology varied from 30 cases of a simple ovarian cyst with torsion, 3 cases of ovarian torsion without any cyst, 7 cases of a dermoid cyst with torsion in all, 1 case of secreting ovarian tumor and 5 cases of a paraovarian cyst with torsion. All patients had a normal tumor marker except 1 girl with a functional ovarian tumor who had elevated LDH and estrogen levels alongwith suppressed LH and FSH. In the initial period of our study we did 1 salpingo-oophorectomy for a suspected complex lesion and two oophorectomies for torsion with a simple cyst. In the later part of our study we performed laparoscopic cystectomy and ovarian preservation in 40 cases, including 7 cases of dermoid, where we performed laparoscopic detorsion with dermoid cystectomy and ovarian preservation in the same sitting. In three cases of chronic torsion who presented to us late, we could not preserve the ovary and had to resort to salpingo-ophorectomy. Histology showed a simple corpus luteal and follicular ovarian cyst in 31 cases, a paraovarian cyst in 5 cases with mature teratoma in 7 cases. Twenty-five patients with ovarian preservation following detorsion were subjected to

  18. Engineered gold nanoparticles for identification of novel ovarian biomarkers

    Giri, Karuna

    Ovarian cancer is a leading cause of cancer related death among women in the US and worldwide. The disease has a high mortality rate due to limited tools available that can diagnose ovarian cancer at an early stage and the lack of effective treatments for disease free survival at late stages. Identification of proteins specifically expressed/overexpressed in ovarian cancer could lead to identification of novel diagnostic biomarkers and therapeutic targets that improve patient outcomes. In this regard, mass spectrometry is a powerful tool to probe the proteome of a cancer cell. It can aid discovery of proteins important for the pathophysiology of ovarian cancer. These proteins in turn could serve as diagnostic and treatment biomarkers of the disease. However, a limitation of mass spectrometry based proteomic analyses is that the technique lacks sensitivity and is biased against detection of low abundance proteins. With current approaches to biomarker discovery, we may therefore be overlooking candidate proteins that are important for ovarian cancer. This study presents a new approach to enrich low abundance proteins and subsequently detect them with mass spectrometry. Gold nanoparticles (AuNPs) and functionalization of their surfaces provide an excellent opportunity to capture and enrich low abundance proteins. First, the study focused on conducting an extensive investigation of the time evolution of nanoparticle-protein interaction and understanding drivers of protein attachment on nanoparticle surface. The adsorption of proteins to AuNPs was found to be highly dynamic with multiple attachment and detachment events which decreased over time. Initially, electrostatic forces played an important role in protein binding and structurally flexible proteins such as those involved in RNA processing were more likely to bind to AuNPs. More importantly, the feasibility and success of protein enrichment by AuNPs was evaluated. The AuNPs based approach was able to detect

  19. The Functions of Selected Human Rights Institutions and Related Role-Players in the Protection of Human Rights in Zimbabwe

    Howard Chitimira

    2016-12-01

    Full Text Available Various violations of the human rights of ordinary people and human rights defenders have been reported in Zimbabwe since the late 1980s. It is widely acknowledged that such violations have been perpetrated mostly by the government through its different organs for political and other related reasons. Human rights violations were also easily committed against ordinary people and human rights defenders because there was no Constitution that adequately protected such people's fundamental human rights (including their civil and political rights and their socio-economic rights in Zimbabwe. Given this background, the article discusses the protection of human rights in Zimbabwe, in the light of the Zimbabwe Constitution Amendment Act 20 of 2013 (Zimbabwe Constitution 2013. This is done in order to investigate whether the promotion, protection, enforcement and respect for human rights in Zimbabwe has now improved. To this end, the functions of selected national human rights institutions and other related role-players, namely civil society, the judiciary, the law enforcement organs and the Zimbabwe Human Rights Commission, are briefly discussed first. Secondly, the functions of selected regional and international institutions, namely the Southern African Development Community, the African Union and the United Nations are discussed in relation to the protection of human rights in Zimbabwe. Thereafter, concluding remarks and possible recommendations that could be utilised to combat human rights violations and enhance the protection of human rights in Zimbabwe are provided.

  20. An Update on Ovarian Aging and Ovarian Reserve Tests

    Migraci Tosun

    2016-12-01

    Full Text Available Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs provide an indirect estimate of a female�s diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs.

  1. The public and economic aspects of the functioning of protected areas within a commune

    Jaros Henryk

    2015-03-01

    Full Text Available Between 2009 and 2013, research was conducted in the commune offices for the Podlaskie voivodeship which have large areas of protected Natura 2000 sites. The research is repeated every few years and widened to include new communes. The aim of the research was to determine the influence of the protected areas on the economic conditions of the communes. It is widely assumed that protected areas generate income for communes, however the communes claim that they incur large additional costs. The surveyed communes were critical of obligatory legal requirements in relation to the protected areas. It was argued that there are problems with obtaining natural resources and with the establishment of new summer resorts, residential and farm buildings and infrastructure; as well as the use and management of the site. The communes’ benefits incidental to the ownership of the protected area are not clear. As part of the benefits, the protected areas offer an opportunity for tourism development. According to the communes, protected areas generate losses in which the estimated losses are several times higher than the potential income. Studies indicate that the conservation cost factor should be considered in terms of financing the communes from the state budget.

  2. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  3. Incidence of ovarian cancer after hysterectomy: a nationwide controlled follow up.

    Loft, A; Lidegaard, O; Tabor, A

    1997-11-01

    To estimate the risk of developing ovarian cancer after abdominal (total or subtotal) hysterectomy on benign indication. Prospective historical cohort study with 12.5 years of follow up. Denmark, nationwide. All Danish women (aged 0 to 99 years) having undergone hysterectomy with conservation of at least one ovary for a benign indication from 1977 to 1981 (n = 22,135). Follow up was conducted from 1977 to 1991. The reference group included all Danish women who had not undergone hysterectomy, age-standardised according to the hysterectomy group (n = 2,554,872). Registry data derived from the Danish National Register of Patients (diagnoses and operation codes) and the Civil Registration System (information about general population, including time of death). Incidence rate of ovarian cancer, lifetime risk of ovarian cancer, relative risk of ovarian cancer. Seventy-one women developed ovarian cancer on average 7.0 years after hysterectomy and 10,659 women in the reference group had ovarian cancer diagnosed after on average 6.4 years. The incidence rate of ovarian cancer was 0.27 per 1000 person-years in the group that had undergone hysterectomy and 0.34 per 1000 person-years in the general population (age-standardised). The extrapolated lifetime risk of developing ovarian cancer was 2.1% after hysterectomy and 2.7% in the general population (RR 0.78; 95% CI 0.60-0.96). The risk of ovarian cancer is lower among women who have undergone hysterectomy compared with those who have not. The protection seems to decrease with time.

  4. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  5. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function

    Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J.; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

    2013-01-01

    The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and

  6. Multifunctional management of mountain forests - Compromises between the protection and conservation functions

    Marc Fuhr, Nicolas Clouet, Thomas Cordonnier and Frédéric Berger

    2011-03-01

    Full Text Available How can the balance between protection against natural hazards and biodiversity conservation be determined at each stage in forest development? This study provides a number of answers in view of improving multifunctional management.

  7. [Protective effect of Qilin Pills on the reproductive function of oligoasthenospermia rats].

    Zhang, Kai-Shu; Zhou, Fang; An, Qi; Jia, Yan-Fei; Fu, Long-Long; Lu, Wen-Hong; Liang, Xiao-Wei; Shang, Xue-Jun; Gu, Yi-Qun

    2017-09-01

    To study the protective effect of Qilin Pills (QLP) on the reproductive function of rats with oligoasthenospermia (OAS) induced by tripterygium glycosides. Twenty-eight male SD rats were randomly divided into a normal control, an OAS model control, a low-dose QLP, and a high-dose QLP group of equal number. OAS models were made in the latter three groups by intragastrical administration of tripterygium glycosides at 40 mg per kg of the body weight per day, and meanwhile the animals in the low- and high-dose QLP groups were treated with QLP at 1.62 and 3.24 g per kg of the body weight per day, respectively, while those in the OAS model group with normal saline, all for 30 consecutive days. Then all the rats were executed for obtaining the testis weight, testis viscera index, epididymal sperm concentration and motility, reproductive hormone levels, and antioxidation indexes and observation of the histomorphological changes of the testis tissue by HE staining. After 30 days of intervention, the low- and high-dose QLP groups, as compared with the OAS model controls, showed significantly improved epididymal sperm concentration ([14.57 ± 3.95] and [39.71 ± 11.31] vs [4.71 ± 1.25] ×10⁶/ml, P <0.05) and motility ([3.71 ± 1.11] and [4.29 ± 1.80] vs [0.57 ± 0.53]%, P <0.05), increased levels of sex hormone binding globulin (SHBG) ([94.83 ± 11.17] and [88.05 ± 9.21] vs [56.74 ± 8.29] nmol/L, P <0.05) and free testosterone (FT) ([27.27 ± 3.63] and [32.80 ± 2.51] vs [22.81 ± 2.75] nmol/L, P <0.05), decreased level of follicle-stimulating hormone (FSH) ([1.49 ± 0.62] and [1.12 ± 0.83] vs [1.71 ± 0.52] mIU/ml, P <0.05), but no significant change in the total testosterone (TT) level. Meanwhile, the level of superoxide dismutase (SOD) was markedly elevated in the low- and high-dose QLP groups in comparison with the OAS model control group ([277.14 ± 15.84] and [299.60 ± 20.83] vs [250.04 ± 31

  8. An evaluation model of protective function in forest management planning: slope stability in regard to shallow landslide events

    2006-01-01

    Full Text Available The evaluation of forest protective function has been divided into four main branches according to the different types of instability phenomena (landslide events, erosion, floods, avalanches. This paper presents the first module related to landslide events and will be followed by others. Two opposing factors have been considered: instability tendency of a selected land unit and protective function of the vegetation. While the first factor tends to promote landslide events, the second one opposes their occurrence. An expert evaluation of these aspects allows us to derive some qualitative indexes. For each territorial unit, these indexes express the protection value of vegetation, the degree of management restrictions and suitable improvements to the forest cover. Both propension and protective functional character are influenced by many and different parameters which require multidisciplinary competences to correctly evaluate them. Such skills are not easily found in technicians in charge of forest management. The present paper aims to provide a decision making support tool; based on neural network models, it should be able to interpret and simulate the expert knowledge, extending to the "standard" forest technician the opportunity to perform such a kind of evaluation. The neural network training required the identification and characterization of explanatory variables related to both aspects, and the subsequent expert definition of the respective datasets of real classification examples. The descriptive variables were chosen considering the information availability and its compatibility with GIS techniques as well. Model performances have been validated by testing the whole procedure in two sites situated in Antrona valley (Piemonte and Acqualagna (Marche. The results are discussed in detail and put in evidence a good accordance with both field survey and general conceptual assumptions. Future developments will involve similar analysis and

  9. Cryobanking of human ovarian tissue

    Ernst, Erik; Andersen, Anders Nyboe; Andersen, Claus Yding

    2014-01-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond...... an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate...... women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family....

  10. Testosterone for Poor Ovarian Responders

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  11. Oophoropexy for Recurrent Ovarian Torsion

    Jennifer Hartley

    2018-01-01

    Full Text Available A 31-year-old nulliparous patient presents with a three-day history of right sided colicky abdominal pain and associated nausea. This patient has previously presented twice with right sided ovarian torsion with the background of polycystic ovaries in the last two consecutive years. Blood tests were normal. Due to previous history, there was a high index of clinical suspicion that this may be a further torsion. Therefore, the patient was taken to theatre for a diagnostic laparoscopy and a further right sided ovarian torsion was noted. At this time, oophoropexy was performed to the uterosacral ligament to prevent further torsion in order to preserve the patients’ fertility. In this article, we detail this case and also provide a discussion of ovarian torsion including risk factors, presentation, and current thoughts on management.

  12. Ovarian reserve after treatment with alkylating agents during childhood.

    Thomas-Teinturier, Cécile; Allodji, Rodrigue Sétchéou; Svetlova, Ekaterina; Frey, Marie-Alix; Oberlin, Odile; Millischer, Anne-Elodie; Epelboin, Sylvie; Decanter, Christine; Pacquement, Helene; Tabone, Marie-Dominique; Sudour-Bonnange, Helene; Baruchel, André; Lahlou, Najiba; De Vathaire, Florent

    2015-06-01

    impossible to dissociate their individual impacts on ovarian reserve. The number of controls is small, but ovarian volume and AMH levels in survivors were compared with published normal values and results were unchanged. Early detection and follow-up of compromised ovarian function after cancer therapy should help physicians to counsel young survivors about their fertility window. However, longitudinal follow-up is required to determine the rate of progression from low ovarian reserve to premature ovarian failure. La Ligue contre le Cancer (grant no., PRAYN7497). The authors have no competing interests to disclose. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Long non-coding RNA TUG1 regulates ovarian cancer proliferation and metastasis via affecting epithelial-mesenchymal transition.

    Kuang, Defeng; Zhang, Xiaoping; Hua, Shaofang; Dong, Wei; Li, Zhiguo

    2016-10-01

    Ovarian cancer is the fifth leading cause of cancer-related death in women worldwide, and recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in cancer development. However, the role of lncRNAs in ovarian cancer is largely unclear. In this study, we focused on the taurine up-regulated gene 1 (TUG1) and examined its molecular mechanism in ovarian cancer. Here, we reported that TUG1 was up-regulated in ovarian cancer tissues and ovarian cancer cells, and TUG1 expression was positively correlated with tumor grade and FIGO stage. In vitro functional assays (CCK-8 assay, colony formation assay, and cell invasion assay) revealed that knock-down of TUG1 by small RNA inference significantly inhibited cell proliferation, colony formation and cell invasion in ovarian cancer cells. Further experiment showed that knock-down of TUG1 induced cell apoptosis and altered the protein expression levels of apoptosis-related mediators in ovarian cancer cells. More importantly, knock-down of TUG1 also reversed epithelial-mesenchymal transition in ovarian cancer. In summary, our results suggest that knock-down of TUG1 may represent a novel therapeutic strategy for the treatment of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Surface protection in bio-shields via a functional soft skin layer: Lessons from the turtle shell.

    Shelef, Yaniv; Bar-On, Benny

    2017-09-01

    The turtle shell is a functional bio-shielding element, which has evolved naturally to provide protection against predator attacks that involve biting and clawing. The near-surface architecture of the turtle shell includes a soft bi-layer skin coating - rather than a hard exterior - which functions as a first line of defense against surface damage. This architecture represents a novel type of bio-shielding configuration, namely, an inverse structural-mechanical design, rather than the hard-coated bio-shielding elements identified so far. In the current study, we used experimentally based structural modeling and FE simulations to analyze the mechanical significance of this unconventional protection architecture in terms of resistance to surface damage upon extensive indentations. We found that the functional bi-layer skin of the turtle shell, which provides graded (soft-softer-hard) mechanical characteristics to the bio-shield exterior, serves as a bumper-buffer mechanism. This material-level adaptation protects the inner core from the highly localized indentation loads via stress delocalization and extensive near-surface plasticity. The newly revealed functional bi-layer coating architecture can potentially be adapted, using synthetic materials, to considerably enhance the surface load-bearing capabilities of various engineering configurations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Ovarian metastases: Computed tomographic appearances

    Megibow, A.J.; Hulnick, D.H.; Bosniak, M.A.; Balthazar, E.J.

    1985-01-01

    Computed tomographic scans of 34 patients with ovarian metastases were reviewed to assess the radiographic appearances and to correlate these with the primary neoplasms. Primary neoplasms were located in the colon (20 patients), breast (six), stomach (five), small bowel (one), bladder (one), and Wilms tumor of the kidney (one). The radiographic appearance of the metastatic lesions could be described as predominantly cystic (14 lesions), mixed (12 lesions), or solid (seven lesions). The cystic and mixed lesions tended to be larger in overall diameter than the solid. The metastases from gastric carcinoma appeared solid in four of five cases. The metastases from the other neoplasms had variable appearances simulating primary ovarian carcinoma

  16. Thrombosis of right ovarian vein

    Forner, J.; Talens, A.; Flores, M.; Mendez, M.

    2001-01-01

    Ovarian vein thrombosis is a rare postpartum complication (0.1%). It can be fatal, since it can lead to sepsis, pulmonary thromboembolisms and inferior vena cava or renal vein thrombosis. Computed tomography and magnetic resonance imaging are the techniques of choice for its diagnosis, while the value of ultrasound is limited due to its low sensitivity and specificity. We report the case of a woman who, during puerperium, developed thrombosis of right ovarian vein that presented clinical, ultrasonographic and computed tomographic features of appendicitis. We describe the radiological sings and stress the fact that this diagnosis should be suspected in puerperal women. (Author) 9 refs

  17. Polycystic ovarian syndrome management options.

    Bates, G Wright; Propst, Anthony M

    2012-12-01

    Polycystic ovarian syndrome (PCOS) is a disorder of androgen excess and ovarian dysfunction. Hirsutism and elevated free testosterone levels are the most consistent signs of the androgen excess. Irregular, infrequent, or absent menses and infertility are symptoms of ovulatory dysfunction. Obesity is also a feature of this syndrome and contributes to associated metabolic abnormalities. Lifestyle modification should be the first treatment and is effective in reducing the signs and symptoms. The ovulatory infertility associated with PCOS can be overcome in most cases with oral (clomiphene citrate or letrozole) or injectable (gonadotropins) agents. Surgical intervention is reserved for cases resistant to medical management. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

    Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

    2014-12-01

    The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean

  19. Polycystic ovarian disease.

    Raj, S G; Talbert, L M

    1984-01-01

    Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

  20. Immunological comparison of ovarian and colonic CEA

    Burtin, P.; Gendron, M.C.; Maunoury, M.T.; Lamerz, R.; Schnabel, G.

    1982-01-01

    Ovarian and colonic CEA were compared immunologically by means of antisera prepared against each of them. CEAs of both origins were found identical by immunodiffusion methods. In radioimmunological experiments, slight differences were observed between some but not all ovarian CEAs and colonic CEAs and also between different preparations of colonic CEA: no organ specificity of ovarian CEA could be demonstrated. Finally, CEA level was measured in 41 sera of patients with ovarian carcinoma by two radioimmunoassays, one using colonic CEA as tracer and standard and anti-colonic CEA serum, the other using ovarian CEA and anti-ovarian CEA serum: the values given by the two assays were highly correlated (rsub(s) = 0.8107), meaning that an organ specific assay for ovarian CEA is not needed. (Auth.)

  1. Functionalization of Cellulose Fibres with Oxygen Plasma and ZnO Nanoparticles for Achieving UV Protective Properties

    Katja Jazbec

    2015-01-01

    Full Text Available Low-pressure oxygen plasma created by an electrodeless radiofrequency (RF discharge was applied to modify the properties of cellulosic fibrous polymer (cotton in order to improve adsorption properties towards zinc oxide (ZnO nanoparticles and to achieve excellent ultraviolet (UV protective properties of cotton fabric. The chemical and physical surface modifications of plasma-treated cotton fabric were examined by X-ray photoelectron spectroscopy (XPS and scanning electron microscopy (SEM. The mechanical properties of plasma-treated samples were evaluated, measuring strength and elongation of the fabrics. The quantity of zinc on the ZnO-functionalized cotton samples was determined using inductively coupled plasma mass spectrometry (ICP-MS and the effectiveness of plasma treatment for UV protective properties of cotton fabrics was evaluated using UV-VIS spectrometry, measuring the UV protection factor (UPF. The results indicated that longer plasma treatment times cause higher concentration of oxygen functional groups on the surface of fibres and higher surface roughness of fibres. These two conditions are crucial in increasing the content of ZnO nanoparticles on the fibres, providing excellent UV protective properties of treated cotton, with UPF factor up to 65.93.

  2. Distribution and protective function of pituitary adenylate cyclase-activating polypeptide (PACAP in the retina

    Tomoya eNakamachi

    2012-11-01

    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP, which is found in 27- or 38-amino acid forms, belongs to the VIP/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues, with PACAP known to exert a protective effect against several types of neural damage. The retina is considered to be part of the central nervous system, and retinopathy is a common cause of profound and intractable loss of vision. This review will examine the expression and morphological distribution of PACAP and its receptors in the retina, and will summarize the current state of knowledge regarding the protective effect of PACAP against different kinds of retinal damage, such as that identified in association with diabetes, ultraviolet light, hypoxia, optic nerve transection, and toxins. This article will also address PACAP-mediated protective pathways involving retinal glial cells.

  3. Effects of three different types of antifreeze proteins on mouse ovarian tissue cryopreservation and transplantation.

    Jaewang Lee

    Full Text Available Ovarian tissue (OT cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, the damage incurred at different steps during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function.This study was designed to investigate the beneficial effects of different antifreeze proteins (AFPs on mouse ovarian tissue cryopreservation and transplantation.Ovaries were obtained from 5-week-old B6D2F1 mice, and each ovary was cryopreserved using two-step vitrification and four-step warming procedures. In Experiment I, ovaries were randomly allocated into fresh, vitrification control, and nine experimental groups according to the AFP type (FfIBP, LeIBP, type III and concentration (0.1, 1, 10 mg/mL used. After vitrification and warming, 5,790 ovarian follicles were evaluated using histology and TUNEL assays, and immunofluorescence for τH2AX and Rad51 was used to detect DNA double-strand breaks (DSBs and repair (DDR, respectively. In Experiment II, 20 mice were randomly divided into two groups: one where the vitrification and warming media were supplemented with 10 mg/mL LeIBP, and the other where media alone were used (control. Ovaries were then autotransplanted under both kidney capsules 7 days after vitrification together with the addition of 10 mg/mL LeIBP in the vitrification-warming media. After transplantation, the ovarian follicles, the percentage of apoptotic follicles, the extent of the CD31-positive area, and the serum FSH levels of the transplanted groups were compared.In Experiment I, the percentage of total grade 1 follicles was significantly higher in the 10 mg/mL LeIBP group than in the vitrification control, while all AFP-treated groups had significantly improved grade 1 primordial follicle numbers compared with those of the vitrification control. The number of apoptotic (TUNEL

  4. Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice.

    Zhang, Jinjin; Lai, Zhiwen; Shi, Liangyan; Tian, Yong; Luo, Aiyue; Xu, Zheyuan; Ma, Xiangyi; Wang, Shixuan

    2018-05-22

    Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging.

  5. Functional safeguards for computers for protection systems for Savannah River reactors

    Kritz, W.R.

    1977-06-01

    Reactors at the Savannah River Plant have recently been equipped with a ''safety computer'' system. This system utilizes dual digital computers in a primary protection system that monitors individual fuel assembly coolant flow and temperature. The design basis for the (SRP safety) computer systems allowed for eventual failure of any input sensor or any computer component. These systems are routinely used by reactor operators with a minimum of training in computer technology. The hardware configuration and software design therefore contain safeguards so that both hardware and human failures do not cause significant loss of reactor protection. The performance of the system to date is described

  6. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  7. A draft map of the human ovarian proteome for tissue engineering and clinical applications.

    Ouni, Emna; Vertommen, Didier; Chiti, Maria Costanza; Dolmans, Marie-Madeleine; Amorim, Christiani Andrade

    2018-02-23

    Fertility preservation research in women today is increasingly taking advantage of bioengineering techniques to develop new biomimetic materials and solutions to safeguard ovarian cell function and microenvironment in vitro and in vivo. However, available data on the human ovary are limited and fundamental differences between animal models and humans are hampering researchers in their quest for more extensive knowledge of human ovarian physiology and key reproductive proteins that need to be preserved. We therefore turned to multi-dimensional label-free mass spectrometry to analyze human ovarian cortex, as it is a high-throughput and conclusive technique providing information on the proteomic composition of complex tissues like the ovary. In-depth proteomic profiling through two-dimensional liquid chromatography-mass spectrometry, western blot, histological and immunohistochemical analyses, and data mining helped us to confidently identify 1,508 proteins. Moreover, our method allowed us to chart the most complete representation so far of the ovarian matrisome, defined as the ensemble of extracellular matrix proteins and associated factors, including more than 80 proteins. In conclusion, this study will provide a better understanding of ovarian proteomics, with a detailed characterization of the ovarian follicle microenvironment, in order to enable bioengineers to create biomimetic scaffolds for transplantation and three-dimensional in vitro culture. By publishing our proteomic data, we also hope to contribute to accelerating biomedical research into ovarian health and disease in general. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Protection of the female reproductive system from natural and artificial insults

    Tilly, Jonathan L.; Kolesnick, Richard N.

    2010-12-14

    Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

  9. Final report for LDRD Project 93633 : new hash function for data protection.

    Draelos, Timothy John; Dautenhahn, Nathan; Schroeppel, Richard Crabtree; Tolk, Keith Michael; Orman, Hilarie (PurpleStreak, Inc.); Walker, Andrea Mae; Malone, Sean; Lee, Eric; Neumann, William Douglas; Cordwell, William R.; Torgerson, Mark Dolan; Anderson, Eric; Lanzone, Andrew J.; Collins, Michael Joseph; McDonald, Timothy Scott; Caskey, Susan Adele

    2009-03-01

    The security of the widely-used cryptographic hash function SHA1 has been impugned. We have developed two replacement hash functions. The first, SHA1X, is a drop-in replacement for SHA1. The second, SANDstorm, has been submitted as a candidate to the NIST-sponsored SHA3 Hash Function competition.

  10. Improvement of the Cubic Spline Function Sets for a Synthesis of the Axial Power Distribution of a Core Protection System

    Koo, Bon-Seung; Lee, Chung-Chan; Zee, Sung-Quun

    2006-01-01

    Online digital core protection system(SCOPS) for a system-integrated modular reactor is being developed as a part of a plant protection system at KAERI. SCOPS calculates the minimum CHFR and maximum LPD based on several online measured system parameters including 3-level ex-core detector signals. In conventional ABB-CE digital power plants, cubic spline synthesis technique has been used in online calculations of the core axial power distributions using ex-core detector signals once every 1 second in CPC. In CPC, pre-determined cubic spline function sets are used depending on the characteristics of the ex-core detector responses. But this method shows an unnegligible power distribution error for the extremely skewed axial shapes by using restrictive function sets. Therefore, this paper describes the cubic spline method for the synthesis of an axial power distribution and it generates several new cubic spline function sets for the application of the core protection system, especially for the severely distorted power shapes needed reactor type

  11. High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

    Wang, Yu-Fang; Li, Jiao-Xing; Sun, Xun-Sha; Lai, Rong; Sheng, Wen-Li

    2018-05-01

    Objective We aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke. Methods We retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed. Results Men had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome. Conclusions Our study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

  12. The protective layer of biofilm : A repellent function for a new class of amphiphilic proteins

    Kovacs, Akos T.; van Gestel, Jordi; Kuipers, Oscar P.

    Bacteria can survive harsh conditions when growing in complex communities of cells known as biofilms. The matrix of the biofilm presents a scaffold where cells are attached to each other and to the surface. The biofilm matrix is also a protective barrier that confers tolerance against various

  13. Riparian Forest Buffers - Function for Protection and Enhancement of Water Resources

    David J. Welsch

    1991-01-01

    Streamside forests are crucial to the protection and enhancement of the water resources of the Eastern United States. They are extremely complex ecosystems that help provide optimum food and habitat for stream communities as well as being useful in mitigating or controlling nonpoint source pollution (NPS). Used as a component of an integrated management system...

  14. Structural and functional analysis of lysosomal ss-galactosidase and its relation to the protective protein.

    H. Morreau (Hans)

    1992-01-01

    textabstractLysosomal B-galactosidase is the glycosidase, that cleaves B-linked galactosyl mmenes from a variety of natural and synthetic substrates. In normal tissues of various species this enzyme appears to associate with two other hydrolases, N-acetyl-o:-neuraminidase and the protective protein.

  15. Eco-friendly design of scour protection: potential enhancement of ecological functioning in offshore wind farms

    Lengkeek, Wouter; Didderen, K.; Teunis, M.; Driessen, F.; Coolen, J.W.P.; Bos, O.G.; Vergouwen, S.A.; Raaijmakers, T.; Vries, de M.B.; Koningsveld, van M.

    2017-01-01

    The aim of this study is to explore the possibilities to implement ‘Building with North Sea Nature’ in offshore infrastructures in the North Sea by providing guidelines for the eco-friendly design of scour protection structures around monopiles in planned wind farms to enhance ecological

  16. SYNOPTIC ASSESSMENT OF WETLAND FUNCTION: A PLANNING TOOL FOR PROTECTION OF WETLAND SPECIES DIVERSITY

    We present a synoptic assessment intended to maximize the benefits to wetland species biodiversity gained through Clean Water Act regulatory efforts within 225 sub-basins in Missouri, Iowa, Nebraska and Kansas (U.S. Environmental Protection Agency, Region 7), USA. Our assessment...

  17. Prevention of Self-Handicapping--The Protective Function of Mastery Goals

    Schwinger, Malte; Stiensmeier-Pelster, Joachim

    2011-01-01

    Drawing on modern diathesis-stress theories which suggest a multiplicative approach to determine one's personal vulnerability status, we posit that the degree of an individual's vulnerability for using self-handicapping strategies in case of self-threatening events depends on the interaction between different vulnerability and protective factors.…

  18. Ovarian cyst fluid of serous ovarian tumors contains large quantities of the brain amino acid N-acetylaspartate.

    Kolwijck, E.; Wevers, R.A.; Engelke, U.F.H.; Woudenberg, J.; Bulten, J.; Blom, H.J.; Massuger, L.F.A.G.

    2010-01-01

    BACKGROUND: In humans, N-acetyl L-aspartate (NAA) has not been detected in other tissues than the brain. The physiological function of NAA is yet undefined. Recently, it has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation. METHODOLOGY AND PRINCIPAL FINDINGS: Using Gas Chromatography-Mass Spectrometry, we demons...

  19. Ovarian stimulation and embryo quality

    Baart, Esther; Macklon, Nick S.; Fauser, Bart J. C. M.

    To Study the effects of different ovarian stimulation approaches on oocyte and embryo quality, it is imperative to assess embryo quality with a reliable and objective method. Embryos rated as high quality by standardized morphological assessment are associated with higher implantation and pregnancy

  20. CA125 in ovarian cancer

    Duffy, M J; Bonfrer, J M; Kulpa, J

    2005-01-01

    women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease...

  1. Ovarian Cancer Risk Prediction Models

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Ovarian cancer and body size

    Mosgaard, Berit Jul

    2012-01-01

    Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished...

  3. Ultrasound in evaluating ovarian reserve

    Eman Ahmaed Shawky Sabek

    2015-12-01

    Full Text Available The objective of this study was to compare the diagnostic accuracy of transvaginal ultrasound (TVS, as a less invasive technique instead of hormonal assay to evaluate the ovarian reserve. This study included fifty-five females with breast cancer and we compared the ovarian reserve for these patients by hormonal assay through measuring the serum AntiMullerian Hormone (AMH level and follicular stimulating hormone (FSH level before and after chemotherapy, and by transvaginal ultrasound through the ovarian volume (OV calculation and counting the Antral follicles (AFC before and after chemotherapy treatment. There was decline in the AntiMullerian Hormone level after chemotherapy by 27 ± 11.19% and decrease in the Antral follicle counts by 21 ± 13.43%. In conclusion there was strong relation between AMH level and AFC which makes the use of transvaginal ultrasound is a reliable alternative method to the hormonal assay to detect the ovarian reserve.

  4. Ovarian irradiation in recurrent endometriosis

    Kochbati, L.; Chaari, N.; Besbes, M.; Maalej, M.; Neji, K.; Ben Amara, F.; Ben Romdhane, N.K.

    2005-01-01

    We describe a case of a young woman with a history of an aplastic anaemia in which pelvic radiotherapy was used successfully in the management of a recurrent and inoperable endometriosis. The use of therapeutic pelvic or ovarian irradiation in endometriosis may be considered, when surgical and medical treatments have been exhausted and have failed. (authors)

  5. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

    Deirdre Therese Little MBBS, DRANZCOG, FACRRM

    2014-10-01

    Full Text Available Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

  6. Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

    Pirgon, Ozgur; Sivrice, Cigdem; Demirtas, Hakan; Dundar, Bumin

    2016-01-01

    We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH Hashimoto thyroiditis (HT). This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

  7. ACTIVITY OF NATURAL KILLER CELLS IN BIOLOGICAL FLUIDS FROM PATIENTS WITH COLORECTAL AND OVARIAN CANCERS

    N. V. Yunusova

    2017-01-01

    Full Text Available Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009, 5 patients with benign ovarian tumors (BOTs, and 15 patients with colorectal cancer (T2–4N0–2M0 . The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB (CD56 + CD107a + GB + PF- was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF- was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p<0.05. The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant

  8. Ovarian cysts on prenatal MRI

    Nemec, Ursula; Nemec, Stefan F.; Bettelheim, Dieter; Brugger, Peter C.; Horcher, Ernst; Schöpf, Veronika; Graham, John M.; Rimoin, David L.; Weber, Michael; Prayer, Daniela

    2012-01-01

    Objective: Ovarian cysts are the most frequently encountered intra-abdominal masses in females in utero. They may, at times, require perinatal intervention. Using magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US) in prenatal diagnosis, we sought to demonstrate the ability to visualize ovarian cysts on prenatal MRI. Materials and methods: This retrospective study included 17 fetal MRI scans from 16 female fetuses (23–37 gestational weeks) with an MRI diagnosis of ovarian cysts after suspicious US findings. A multiplanar MRI protocol was applied to image and to characterize the cysts. The US and MRI findings were compared, and the prenatal findings were compared with postnatal imaging findings or histopathology. Results: Simple ovarian cysts were found in 10/16 cases and complex cysts in 7/16 cases, including one case with both. In 11/16 (69%) cases, US and MRI diagnoses were in agreement, and, in 5/16 (31%) cases, MRI specified or expanded the US diagnosis. In 6/16 cases, postnatal US showed that the cysts spontaneously resolved or decreased in size, and in 1/16 cases, postnatal imaging confirmed a hemorrhagic cyst. In 4/16 cases, the prenatal diagnoses were confirmed by surgery/histopathology, and for the rest, postnatal correlation was not available. Conclusion: Our results illustrate the MRI visualization of ovarian cysts in utero. In most cases, MRI will confirm the US diagnosis. In certain cases, MRI may provide further diagnostic information, additional to US, which is the standard technique for diagnosis, monitoring, and treatment planning.

  9. Ovarian cysts on prenatal MRI

    Nemec, Ursula [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Nemec, Stefan F., E-mail: stefan.nemec@meduniwien.ac.at [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, PACT Suite 400, Los Angeles, CA 90048 (United States); Bettelheim, Dieter [Department of Obstetrics and Gynaecology, Division of Prenatal Diagnosis and Therapy, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University Vienna, Waehringerstrasse 13, A-1090 Vienna (Austria); Horcher, Ernst [Department of Pediatric Surgery, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schoepf, Veronika [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Graham, John M.; Rimoin, David L. [Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, PACT Suite 400, Los Angeles, CA 90048 (United States); Weber, Michael; Prayer, Daniela [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2012-08-15

    Objective: Ovarian cysts are the most frequently encountered intra-abdominal masses in females in utero. They may, at times, require perinatal intervention. Using magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US) in prenatal diagnosis, we sought to demonstrate the ability to visualize ovarian cysts on prenatal MRI. Materials and methods: This retrospective study included 17 fetal MRI scans from 16 female fetuses (23-37 gestational weeks) with an MRI diagnosis of ovarian cysts after suspicious US findings. A multiplanar MRI protocol was applied to image and to characterize the cysts. The US and MRI findings were compared, and the prenatal findings were compared with postnatal imaging findings or histopathology. Results: Simple ovarian cysts were found in 10/16 cases and complex cysts in 7/16 cases, including one case with both. In 11/16 (69%) cases, US and MRI diagnoses were in agreement, and, in 5/16 (31%) cases, MRI specified or expanded the US diagnosis. In 6/16 cases, postnatal US showed that the cysts spontaneously resolved or decreased in size, and in 1/16 cases, postnatal imaging confirmed a hemorrhagic cyst. In 4/16 cases, the prenatal diagnoses were confirmed by surgery/histopathology, and for the rest, postnatal correlation was not available. Conclusion: Our results illustrate the MRI visualization of ovarian cysts in utero. In most cases, MRI will confirm the US diagnosis. In certain cases, MRI may provide further diagnostic information, additional to US, which is the standard technique for diagnosis, monitoring, and treatment planning.

  10. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  11. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    Zun-Jing Liu; Wei Liu; Lei Liu; Cheng Xiao; Yu Wang; Jing-Song Jiao

    2013-01-01

    Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPAR ? agonist in that it upregulated PPAR ? expression and PPAR ? -PPRE binding activity. Administration of curcumin markedly dec...

  12. 2-Mercaptobenzothiazole doped chitosan/11-alkanethiolate acid composite coating: Dual function for copper protection

    Bao Qi; Zhang Dun; Wan Yi

    2011-01-01

    Chitosan (CS) hydrogel loaded with the well-known corrosion inhibitor 2-mercaptobenzothiazole (MBT) has been introduced into a composite coating to improve copper protection. This composite coating, which has both anticorrosion and antibacterial properties, was fabricated onto the surface of copper by combining a simple self-assembled monolayer technique with a sol-gel method. The anti-corrosion ability of the coating in 3.5 wt.% NaCl solution was investigated by electrochemical methods including potentiodynamic polarization and electrochemical impedance spectroscopy. The protection efficiency of the coating is 97.70%, calculated on the basis of the corrosion current density. The stability and integrity of the composite coating were evaluated by field emission scanning electron microscopy (FESEM) and energy dispersive spectrometry (EDS). The FESEM and EDS results suggest that the composite coating endows the copper substrate with antibacterial properties, as untreated bare copper underwent microbiologically influenced corrosion in the presence of sulphate reducing bacteria (SRB). This antibacterial feature was further confirmed by the SRB culture method. In a 3.5% NaCl solution and highly corrosive SRB culture media, the as-prepared CS based composite coating gave corrosion protection by exhibiting better barrier effects against the attack of aggressive environments.

  13. Maternal Prenatal Psychological Distress and Preschool Cognitive Functioning: the Protective Role of Positive Parental Engagement.

    Schechter, Julia C; Brennan, Patricia A; Smith, Alicia K; Stowe, Zachary N; Newport, D Jeffrey; Johnson, Katrina C

    2017-02-01

    Considerable animal research and available human studies suggest that psychological distress experienced by mothers during gestation is associated with later neurodevelopmental deficits in offspring; however, little research has examined potential protective factors that might mitigate this risk. The current study examined the impact of maternal prenatal psychological distress during pregnancy on cognitive outcomes in preschoolers (ages 2.5-5 years) and positive parenting as a potential protective factor. Mother-child dyads (N = 162, mean child age = 44 months, 49 % female) were recruited from a longitudinal cohort of women who had previously participated in a study of maternal mood disorders during pregnancy. Maternal prenatal distress was assessed with multiple measures collected throughout pregnancy. During a follow-up visit, mothers were interviewed about their psychological symptoms since the birth of the child, parenting behaviors were recorded during a parent-child interaction, and children's cognitive abilities were measured using the Differential Ability Scales, 2nd Edition. Maternal prenatal distress significantly predicted lower general cognitive abilities; however, this relationship was strongest for children whose mothers exhibited low levels of positive engagement and not significant when mothers exhibited high levels of positive engagement. Results suggest that positive parental engagement can protect against the detrimental effects of maternal prenatal distress on preschoolers' cognitive abilities.

  14. Multifunctional AgNPs@Wool: colored, UV-protective and antioxidant functional textiles

    Shabbir, Mohd; Mohammad, Faqeer

    2018-02-01

    Nanomaterials have great impact on textile industry for multifunctional and smart clothing as per the need of present, and further, green nanotechnology is the current hotspot of research and industrial developments. Silver nanoparticles (AgNPs) are synthesized (in situ) by using natural compounds of plant extracts (naphthoquinones, phenolics/flavonoids, polyphenols) as reducing or stabilizing agents, and simultaneously deposited on wool fabric for coloration, UV protection and antioxidant properties. UV-visible spectroscopy is used to monitor the route of biosynthesis of nanoparticles and transmission electron microscopy for morphological characteristics of synthesized AgNPs. Spherical and almost oval-shaped AgNPs were synthesized by naphthoquinones, polyphenols and flavonoids, respectively. Scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction pattern (XRD) and Fourier transform infrared spectroscopy were used for the AgNPs@Wool fabrics characterization. SEM-EDX analysis and XRD patterns confirmed the successful deposition of silver nanoparticles on wool. Coloration characteristics in terms of color strength (K/S) and CIEL*a*b*c*h° values, UV protection abilities in terms of UV transmittance and UV protection factor, and % antioxidant activity of AgNPs@Wool are suggestive of good-to-excellent results.

  15. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    Zun-Jing Liu

    2013-01-01

    Full Text Available Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

  16. Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

    Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

    2018-04-10

    This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

  17. Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress.

    Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

    2016-12-02

    Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

  18. Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress

    Leilei Yu

    2016-12-01

    Full Text Available Aluminum (Al is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

  19. Risk of borderline ovarian tumors among women with benign ovarian tumors

    Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

    2018-01-01

    tumors among women with a benign ovarian tumor. METHODS: This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals...... (CI) were calculated. RESULTS: Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors....... The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes...

  20. Ovarian Cysts and Fertility: Is There a Connection?

    ... Is there a link between ovarian cysts and fertility? Answers from Charles Coddington, M.D. Some ovarian cysts can be associated with decreased fertility. However, it depends on the type of ovarian ...

  1. Bilateral synchronous benign ovarian neoplasm: A rare occurrence

    right ovarian mass, which revealed a left ovarian benign cystic teratoma and a right ovarian ... Women's reproductive health rights need to be encouraged and possibly legislated in our setting. ..... Med J Armed Forces India 2011;67(3):272-.

  2. Risks of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening

    ... black women. Different factors increase or decrease the risk of getting ovarian, fallopian tube, and primary peritoneal ... decrease the number of deaths from ovarian cancer. Risks of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer ...

  3. Psychological functioning in non-clinical young adults: Protective and risk factors for internalizing symptoms

    Mabilia, Diana

    2015-01-01

    The present research proposes the analysis of specific aspects of psychosocial functioning and development with a focus on issues related to internalizing symptoms, attachment styles and interpersonal dimensions of interpersonal functioning. Developmental theories emphasized the importance of transitions, as periods of biologically and socially characterized changes (Arnett, 1997; Gurevitz Stern, 2004; Schulenberg, Magges, Hurrelmann, 1997; Schulenberg & Zarrett, 2006). The development...

  4. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage

    Bachmann, Rosilla F.; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K.

    2009-01-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially media...

  5. L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells

    He Mindi; Xu Shangcheng; Lu Yonghui; Li Li; Zhong Min; Zhang Yanwen; Wang Yuan; Li Min; Yang Ju; Zhang Guangbin; Yu Zhengping; Zhou Zhou

    2011-01-01

    Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl 2 ) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl 2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ m ), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.

  6. Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density.

    Bakhsh, Hanadi; Dei, Metella; Bucciantini, Sandra; Balzi, Daniela; Bruni, Vincenzina

    2015-01-01

    To evaluate biological differences among young subjects with premature ovarian insufficiency (POI) commencing at different stages of life. Retrospective observational study. Careggi University Hospital Participants: One hundred sixty-two females aged between 15 and 29 years with premature ovarian insufficiency. Data were collected as a retrospective chart review of baseline evaluation at diagnosis of premature ovarian insufficiency (POI). About 162 participants were divided into four groups based on gynecological age. Two primary outcome variables (uterine development and bone mineral density (BMD)) were analyzed in terms of differences among groups and in a multivariate logistic regression analysis. Uterine development was clearly jeopardized when estrogen insufficiency started at a very young age. Total body BMD showed significant differences among the four groups studied, clearly corresponding to the duration of ovarian function. Data were discussed in relation to the choice of hormone replacement therapy regimens.

  7. Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women

    Li, Shuxia; Zhu, Dongyi; Duan, Hongmei

    2017-01-01

    As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from...... interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS...... in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol...

  8. Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women.

    Li, Shuxia; Zhu, Dongyi; Duan, Hongmei; Ren, Anran; Glintborg, Dorte; Andersen, Marianne; Skov, Vibe; Thomassen, Mads; Kruse, Torben; Tan, Qihua

    2017-03-28

    As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.

  9. Cryopreservation of ovarian tissue for fertility preservation in young female oncological patients.

    Andersen, Claus Yding; Kristensen, Stine Gry; Greve, Tine; Schmidt, Kirsten Tryde

    2012-05-01

    Girls and women suffering from a cancer that requires treatment with gonadotoxic drugs may experience cessation of reproductive function as a side effect due to obliteration of the ovarian pool of follicles. Techniques are now available for fertility preservation, such as cryopreservation of mature oocytes, embryos or ovarian cortical tissue. Whereas collection of mature oocytes and embryos requires at least a 2-week period, ovarian tissue may on short notice be frozen prior to treatment and can be transplanted back into women with ovarian failure. Transplanted frozen/thawed tissue supports survival and growth of follicles, giving rise to menstrual cycles and hormone production for several years. Worldwide, the procedure has resulted in the birth of 15 healthy children. Many cancer patients including girls and young women want fertility preservation, and the techniques are now being further developed and implemented in several centers.

  10. Fertility preservation in pre-pubertal girls with cancer: the role of ovarian tissue cryopreservation.

    Wallace, W Hamish B; Kelsey, Thomas W; Anderson, Richard A

    2016-01-01

    With the increasing numbers of survivors of cancer in young people, future fertility and ovarian function are important considerations that should be discussed before treatment commences. Some young people, by nature of the treatment they will receive, are at high risk of premature ovarian insufficiency and infertility. For them, ovarian tissue cryopreservation (OTC) is one approach to fertility preservation that remains both invasive and for young patients experimental. There are important ethical and consent issues that need to be explored and accepted before OTC can be considered established in children with cancer. In this review we have discussed a framework for patient selection which has been shown to be effective in identifying those patients at high risk of premature ovarian insufficiency and who can be offered OTC safely. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

    Narod Steven

    2004-02-01

    Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

  12. Study the ovarian function in Awassi ewes

    Zarkawi, M.

    1996-03-01

    An experiment was carried out on local Awassi ewes to study the reproductive performance, progesteron concentrations, accuracy of pregnacy diagnosis and other reproduction related criteria of Awassi ewes using radioimunoassay (RIA). A total of 18 nulliparous Awassi ewes, aged about 1 year and weighing on average 36.9 Kg was used. Live-weight changes were recorded weekly. Blood samples (5 ml) were collected from the jugular vein for about 1 year at 10.00h. Sera were prepared and stored at - 20 deg until assyed. The FAO/IAEA progesterone RIA kits were used. Two ewes aborted after about three-and-a-half months of pregnancy due to mechanical reasons. The remaining ewes (16) lambed between 30th November 1994 and 22nd February 1995. Sex ratio was 1:1 (8 males: 8 females). Average birth weights for both sexes was 5210 ± 525 g. Average birth-weight was higher in males than females. Average male birth-weights was 5338 ± 515 g, (4600 - 6000 g) whereas was 5083 ± 538 g, (4180 - 5700 g) for female lambs. Average basal pre-mating progesterone concentration was 0.60 ± 0.42 n mol/l (0-1.7 n mol/l). Average maximum progesterone concentration during the luteal phase in non-pregnant ewes was 11.1 ± 3.1 n mol/l (5.8 -18.00 n mol/l). Average maximum progesterone concentration during gestation was 58.4 ± 20.9 n mol/l (29.25 - 100.00 n mol/l). The accuracy of pregnancy diagnosis at around 21 days post mating using RIA was 100%. It is concluded that RIA could be used for progesterone determination in Awassi sheep successfully, and that more research work on other aspects of reproduction in Awassi sheep should be carried out. (Author). 29 refs., 47 tabs., 5 figs

  13. Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in Sprague-Dawley rats: An experimental study

    Gbotolorun Stella Chinwe

    2018-02-01

    Full Text Available Background: Cisplatin is a potent antineoplastic agent for many cancers but causes several levels of gonadal damage. Ovarian toxicity is a major concern of young cancer patients undergoing chemotherapy. Objective: This study sought to examine the effect of Cisplatin and Resveratrol supplementation on ovarian function in Sprague-Dawley rats. Materials and Methods: In this experimental study, 45 cyclic Sprague-Dawley rats with an average weight of 160 gr were divided into 9 groups (n=5/group. Group 1 was used as control and received distilled water. Groups 2 and 9 received Cisplatin only. Groups 3, 4, and 5 received different doses of Resveratrol after a single dose of Cisplatin. Groups 6, 7, and 8 received Resveratrol before Cisplatin. At sacrifice, the ovary was analyzed for histopathology, biochemical indices of oxidation and hormonal assay. Results: Relative and absolute organ weights were notably increased (p=0.001, 0.01 in the prophylactic groups relative to the groups that received Resveratrol after Cisplatin. Also, glutathione, superoxide dismutase and catalase were significantly increased (p=0.047, 0.01, 0.023 in a dose-dependent manner when compared to Cisplatin group only. Malondialdehyde decreased significantly (p=0.001 in the groups that received high dose Resveratrol compared with the control and Cisplatin alone groups. Although oestrogen showed no significant difference within the groups (p=0.48, Resveratrol significantly increased progesterone, follicle stimulating hormone and luteinizing hormone levels (p=0.007, 0.001, 0.006 at high doses when compared with Cisplatin alone groups. Ovarian histoarchitecture was best preserved in the prophylactic groups in a dose-dependent manner. Conclusion: Resveratrol supplementation confers protection and preserves ovarian follicles from Cisplatin toxicity in Sprague-Dawley rats.

  14. Lysine demethylase inhibition protects pancreatic β cells from apoptosis and improves β-cell function

    Backe, Marie Balslev; Andersson, Jan Legaard; Bacos, Karl

    2018-01-01

    ) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress. Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting......Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs...

  15. Management of ovarian cysts in infants

    Yan Xue-qiang

    2015-01-01

    Full Text Available Background: To discuss the experience of diagnosis and treatment of ovarian cyst in infants. Materials and Methods: A retrospective review was conducted on 20 infants who suffered from ovarian cyst. Results: There were no dysplasia ovarian was found in children which were preoperatively diagnosed simplex cyst. Within thirteen children preoperatively detected mixed cystic-solid lesion, six cases ovarian cysts disappeared and two cases underwent poor blood supply in the following time. Conclusion: Adverse effects for ovarian cyst in infants can be prevented by agressive surgical intervention. Harmful effects of ovarian cyst can be prevented by positive surgical intervention despite the diagnostic difficulties in children with clinical symptoms of this condition.

  16. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  17. Antiangiogenic and Antitumor Effects of Src Inhibition in Ovarian Carcinoma

    Han, Liz Y.; Landen, Charles N.; Trevino, Jose G.; Halder, Jyotsnabaran; Lin, Yvonne G.; Kamat, Aparna A.; Kim, Tae-Jin; Merritt, William M.; Coleman, Robert L.; Gershenson, David M.; Shakespeare, William C.; Wang, Yihan; Sundaramoorth, Raji; Metcalf, Chester A.; Dalgarno, David C.; Sawyer, Tomi K.; Gallick, Gary E.; Sood, Anil K.

    2011-01-01

    Src, a nonreceptor tyrosine kinase, is a key mediator for multiple signaling pathways that regulate critical cellular functions and is often aberrantly activated in a number of solid tumors, including ovarian carcinoma. The purpose of this study was to determine the role of activated Src inhibition on tumor growth in an orthotopic murine model of ovarian carcinoma. In vitro studies on HeyA8 and SKOV3ip1 cell lines revealed that Src inhibition by the Src-selective inhibitor, AP23846, occurred within 1 hour and responded in a dose-dependent manner. Furthermore, Src inhibition enhanced the cytotoxicity of docetaxel in both chemosensitive and chemoresistant ovarian cancer cell lines, HeyA8 and HeyA8-MDR, respectively. In vivo, Src inhibition by AP23994, an orally bioavailable analogue of AP23846, significantly decreased tumor burden in HeyA8 (P = 0.02), SKOV3ip1 (P = 0.01), as well as HeyA8-MDR (P < 0.03) relative to the untreated controls. However, the greatest effect on tumor reduction was observed in combination therapy with docetaxel (P < 0.001, P = 0.002, and P = 0.01, for the above models, respectively). Proliferating cell nuclear antigen staining showed that Src inhibition alone (P = 0.02) and in combination with docetaxel (P = 0.007) significantly reduced tumor proliferation. In addition, Src inhibition alone and in combination with docetaxel significantly down-regulated tumoral production of vascular endothelial growth factor and interleukin 8, whereas combination therapy decreased the microvessel density (P = 0.02) and significantly affected vascular permeability (P < 0.05). In summary, Src inhibition with AP23994 has potent antiangiogenic effects and significantly reduces tumor burden in preclinical ovarian cancer models. Thus, Src inhibition may be an attractive therapeutic approach for patients with ovarian carcinoma. PMID:16951177

  18. The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target of functional and protective human antibodies against malaria.

    Linda Reiling

    Full Text Available BACKGROUND: Acquired antibodies are important in human immunity to malaria, but key targets remain largely unknown. Plasmodium falciparum reticulocyte-binding-homologue-4 (PfRh4 is important for invasion of human erythrocytes and may therefore be a target of protective immunity. METHODS: IgG and IgG subclass-specific responses against different regions of PfRh4 were determined in a longitudinal cohort of 206 children in Papua New Guinea (PNG. Human PfRh4 antibodies were tested for functional invasion-inhibitory activity, and expression of PfRh4 by P. falciparum isolates and sequence polymorphisms were determined. RESULTS: Antibodies to PfRh4 were acquired by children exposed to P. falciparum malaria, were predominantly comprised of IgG1 and IgG3 subclasses, and were associated with increasing age and active parasitemia. High levels of antibodies, particularly IgG3, were strongly predictive of protection against clinical malaria and high-density parasitemia. Human affinity-purified antibodies to the binding region of PfRh4 effectively inhibited erythrocyte invasion by P. falciparum merozoites and antibody levels in protected children were at functionally-active concentrations. Although expression of PfRh4 can vary, PfRh4 protein was expressed by most isolates derived from the cohort and showed limited sequence polymorphism. CONCLUSIONS: Evidence suggests that PfRh4 is a target of antibodies that contribute to protective immunity to malaria by inhibiting erythrocyte invasion and preventing high density parasitemia. These findings advance our understanding of the targets and mechanisms of human immunity and evaluating the potential of PfRh4 as a component of candidate malaria vaccines.

  19. Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

    Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

    2012-11-01

    Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

  20. Incipient ovarian failure and premature ovarian failure show the same immunological profile

    van Kasteren, YM; von Blomberg, M; Hoek, A; de Koning, C; Lambalk, N; van Montfrans, J; Kuik, J

    PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian

  1. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  2. Unique Case Reports Associated with Ovarian Failure: Necessity of Two Intact X Chromosomes

    Lakshmi Rao Kandukuri

    2012-01-01

    Full Text Available Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months with low level of oestrogen and raised level of Luteinizing Hormone (LH and Follicle Stimulating Hormone (FSH > 20 IU/l occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22 and q28 and (mos,45XO/46,X+ringX involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.

  3. Ovarian Damage during Chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility

    Wendy Marder

    2012-01-01

    Full Text Available Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency (POI due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.

  4. Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

    Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

    2009-11-01

    The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

  5. Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

    Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi; hide

    2016-01-01

    Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential

  6. Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.

    Wang, Jiandong; Ma, Xiaoli; Jones, Hannah M; Chan, Leo Li-Ying; Song, Fang; Zhang, Weiyuan; Bae-Jump, Victoria L; Zhou, Chunxiao

    2014-08-21

    Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.

  7. BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer.

    Habata, Shutaro; Iwasaki, Masahiro; Sugio, Asuka; Suzuki, Miwa; Tamate, Masato; Satohisa, Seiro; Tanaka, Ryoichi; Saito, Tsuyoshi

    2016-07-01

    Paclitaxel in combination with carboplatin improves survival among patients with susceptible ovarian cancers, but no strategy has been established against resistant ovarian cancers. BAG3 (Bcl-2-associated athanogene 3) is one of six BAG family proteins, which are involved in such cellular processes as proliferation, migration and apoptosis. In addition, expression of BAG3 with Mcl-1, a Bcl-2 family protein, reportedly associates with resistance to chemotherapy. Our aim in this study was to evaluate the functional role of BAG3 and Mcl-1 in ovarian cancer chemoresistance and explore possible new targets for treatment. We found that combined expression of BAG3 and Mcl-1 was significantly associated with a poor prognosis in ovarian cancer patients. In vitro, BAG3 knockdown in ES2 clear ovarian cancer cells significantly increased the efficacy of paclitaxel in combination with the Mcl-1 antagonist MIM1, with or without the Bcl-2 family antagonist ABT737. Moreover, BAG3 was found to positively regulate Mcl-1 levels by binding to and inhibiting USP9X. Our data show that BAG3 and Mcl-1 are key mediators of resistance to chemotherapy in ovarian cancer. In BAG3 knockdown ES2 clear ovarian cancer cells, combination with ABT737 and MIM1 enhanced the efficacy of paclitaxel. These results suggest that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers.

  8. PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

    Luo, Shuang, E-mail: luoshuangsch@163.com [Department of Obstetrics and Gynecology, Suining Central Hospital, Suining (China); Wang, Jidong [Department of Gynecology and Obsterics, Jinan Central Hospital, Jinan (China); Ma, Ying [Department of Otorhinolaryngolgy, Suining Central Hospital, Suining (China); Yao, Zhenwei [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Pan, Hongjuan [Department of Gynecology and Obsterics, Zhongshan Hospital, Wuhan (China)

    2015-06-26

    miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence of miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.

  9. Markers of Ovarian Cancer Using a Glycoprotein/Antibody Array

    2014-05-01

    Article dx.doi.org/10.1021/pr400169n | J. Proteome Res. 2013, 12, 3342−33523350 osteopontin fragments for ovarian cancer in urine . Clin. Cancer Res. 2006...absorbent under urea /dithiothreitol denatured environment. Anal. Biochem. 2010, 398